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Sample records for strictly human pathogens

  1. Human pathogen avoidance adaptations

    NARCIS (Netherlands)

    Tybur, J.M.; Lieberman, D.

    2016-01-01

    Over the past few decades, researchers have become increasingly interested in the adaptations guiding the avoidance of disease-causing organisms. Here we discuss the latest developments in this area, including a recently developed information-processing model of the adaptations underlying pathogen

  2. Molecular detection of human bacterial pathogens

    National Research Council Canada - National Science Library

    Liu, Dongyou

    2011-01-01

    .... Molecular Detection of Human Bacterial Pathogens addresses this issue, with international scientists in respective bacterial pathogen research and diagnosis providing expert summaries on current...

  3. Effect of cryopreservation and lyophilization on viability and growth of strict anaerobic human gut microbes.

    Science.gov (United States)

    Bircher, Lea; Geirnaert, Annelies; Hammes, Frederik; Lacroix, Christophe; Schwab, Clarissa

    2018-04-17

    Strict anaerobic gut microbes have been suggested as 'next-generation probiotics' for treating several intestinal disorders. The development of preservation techniques is of major importance for therapeutic application. This study investigated cryopreservation (-80°C) and lyophilization survival and storage stability (4°C for 3 months) of the strict anaerobic gut microbes Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Roseburia intestinalis, Anaerostipes caccae, Eubacterium hallii and Blautia obeum. To improve preservation survival, protectants sucrose and inulin (both 5% w/v) were added for lyophilization and were also combined with glycerol (15% v/v) for cryopreservation. Bacterial fitness, evaluated by maximum growth rate and lag phase, viability and membrane integrity were determined using a standardized growth assay and by flow cytometry as markers for preservation resistance. Lyophilization was more detrimental to viability and fitness than cryopreservation, but led to better storage stability. Adding sucrose and inulin enhanced viability and the proportion of intact cells during lyophilization of all strains. Viability of protectant-free B. thetaiotaomicron, A. caccae and F. prausnitzii was above 50% after cryopreservation and storage and increased to above 80% if protectants were present. The addition of glycerol, sucrose and inulin strongly enhanced the viability of B. obeum, E. hallii and R. intestinalis from 0.03-2% in protectant-free cultures to 11-37%. This is the first study that quantitatively compared the effect of cryopreservation and lyophilization and the addition of selected protectants on viability and fitness of six strict anaerobic gut microbes. Our results suggest that efficiency of protectants is process- and species-specific. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  4. Human diseases associated with fish pathogens

    OpenAIRE

    VATSOS N. Ioannis; ANGELIDIS Panagiotis

    2011-01-01

    Until recently, most cases of humans been affected by fish pathogens, bacterial and parasitic, were limited in certain countries, either due to the inappropriate sanitary measures used in those areas, or due to the local habit of eating raw or undercooked fish. However, as new reliable methods to identify fish pathogens in samples collected from sick humans have been developed, the confirmed cases worldwide have increased. The most common fish bacterial pathogens that can affect humans belong...

  5. The strict liability principle in antidoping rules and the human rights of athletes: an approach critical

    Directory of Open Access Journals (Sweden)

    R.C. Cunha

    2008-01-01

    Full Text Available Back Ground: the human lives in search of overrun at all levels, whether professional, emotional or in their interpersonal relationships. In the middle of sports this search becomes more visible, because hundredths of seconds can make the difference between the podium and the failure. Journals at any moment announces a new case of a positive doping in several sports. Objective: analyse the processes judged for doping in the STJD of the Brazilian athletism and verify if the pronounced sentences are in accordance with the Brazilian Constitution and with the Universal Declaration of the Human Rights. Materials and Methods: 18 cases were reviewed by the use of prohibited substance, between the years 2003 to 2006 by the STJD of Athletism. Results: of the 18 cases examined only 3 were acquitted by the STJD, however, these three, two have met suspension for two years, in order that WADA, not satisfied with the results asked the International Federation (IAAF to analyze them, and after guided them to the Court of Arbitration Sports (CAS. Conclusion: the rule of objective responsibility are not in accordance with the Brazilian Constitution and with the Universal Declaration of the Human Rights, leading athletes to respond irrespective proven their guilt.

  6. Human diseases associated with fish pathogens

    Directory of Open Access Journals (Sweden)

    VATSOS N. Ioannis

    2011-09-01

    Full Text Available Until recently, most cases of humans been affected by fish pathogens, bacterial and parasitic, were limited in certain countries, either due to the inappropriate sanitary measures used in those areas, or due to the local habit of eating raw or undercooked fish. However, as new reliable methods to identify fish pathogens in samples collected from sick humans have been developed, the confirmed cases worldwide have increased. The most common fish bacterial pathogens that can affect humans belong to the genera: Mycobacterium spp. (mainly M. marinum, M. chelonei, M. fortuitum, Nocardia spp., Streptococcus spp (S. iniae, Vibrio spp. (mainly V. vulnificus, V. alginolyticus and V. parahaemolyticus and Aeromonas spp. (mainly A. hydrophila and rarely A. sorbia and A. caviae. Less often, infections of humans with Edwardsiella tarda and Photobacterium damselae sbsp. damselae have been reported. Fish usually act as intermediate hosts to many important parasites of human, as for example the tapeworm Diphyllobothrium latum. To fish, these parasites cause no or little damage, as they are usually found encysted in many fish tissues. Of particular interest are someanisakids (e.g. Anisakis simplex and Pseudoterranova decipiens which can produce some thermostable allergens. Most of the above pathogens can infect humans through skin wounds or after ingesting infected fish. Compromised immune system of the infected humans may result in extensive spread of the pathogens within the body, often causing death.There are no fish viruses or fungi that can affect humans. Fish can also act as carriers for human pathogens, such as Salmonella spp., Escherichia coli and Listeria spp. Recently, few human pathogens have also been isolated from the internal organs of fish, as for example Brucella melitensis. The effects of these human pathogens to fish are still not known.

  7. RNAi suppressors encoded by pathogenic human viruses

    NARCIS (Netherlands)

    de Vries, Walter; Berkhout, Ben

    2008-01-01

    RNA silencing or RNAi interference (RNAi) serves as an innate antiviral mechanism in plants, fungi and animals. Human viruses, like plant viruses, encode suppressor proteins or RNAs that block or modulate the RNAi pathway. This review summarizes the mechanisms by which pathogenic human viruses

  8. Sexual Reproduction of Human Fungal Pathogens

    Science.gov (United States)

    Heitman, Joseph; Carter, Dee A.; Dyer, Paul S.; Soll, David R.

    2014-01-01

    We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms. PMID:25085958

  9. Human pathogen subversion of antigen presentation.

    Science.gov (United States)

    Brodsky, F M; Lem, L; Solache, A; Bennett, E M

    1999-04-01

    Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

  10. Pathogens spectrum of deep human mycosis

    Directory of Open Access Journals (Sweden)

    A. B. Kulko

    2012-01-01

    Full Text Available The article describes characteristics of two different etiology groups of deep human mycosis — extremely dangerous endemic deep mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, penicilliosis due to Penicillium marneffei and opportunistic deep mycosis (candidiasis, cryptococcosis, aspergillosis, mucormycosis. Information on fungal pathogens and antifungal agents is presented. The own results of cultural studies obtained during pneumomycosis diagnosis in patients with tuberculosis are shown.

  11. Novel detection techniques for human pathogens that contaminate poultry.

    Science.gov (United States)

    Mandrell, R E; Wachtel, M R

    1999-06-01

    Poultry products are presumed to be a major contributor to human foodborne illness due to their high frequency of contamination with pathogens Salmonella spp. and Campylobacter spp. This has stimulated the development of more sensitive and rapid methods for identifying pathogens present in poultry. These new methods include immunomagnetic separation of pathogen, PCR amplification of pathogen-specific sequences, pathogen-specific DNA and RNA probes, and identification of pathogen-specific ions by mass spectrometry.

  12. Strict confluent drawing

    Directory of Open Access Journals (Sweden)

    David Eppstein

    2016-01-01

    Full Text Available We define strict confluent drawing, a form of confluent drawing in which the existence of an edge is indicated by the presence of a smooth path through a system of arcs and junctions (without crossings, and in which such a path, if it exists, must be unique. We prove that it is NP-complete to determine whether a given graph has a strict confluent drawing but polynomial to determine whether it has an outerplanar strict confluent drawing with a fixed vertex ordering (a drawing within a disk, with the vertices placed in a given order on the boundary.

  13. Human Milk Glycoproteins Protect Infants Against Human Pathogens

    Science.gov (United States)

    Liu, Bo

    2013-01-01

    Abstract Breastfeeding protects the neonate against pathogen infection. Major mechanisms of protection include human milk glycoconjugates functioning as soluble receptor mimetics that inhibit pathogen binding to the mucosal cell surface, prebiotic stimulation of gut colonization by favorable microbiota, immunomodulation, and as a substrate for bacterial fermentation products in the gut. Human milk proteins are predominantly glycosylated, and some biological functions of these human milk glycoproteins (HMGPs) have been reported. HMGPs range in size from 14 kDa to 2,000 kDa and include mucins, secretory immunoglobulin A, bile salt-stimulated lipase, lactoferrin, butyrophilin, lactadherin, leptin, and adiponectin. This review summarizes known biological roles of HMGPs that may contribute to the ability of human milk to protect neonates from disease. PMID:23697737

  14. Strict tropism for CD71+/CD234+human reticulocytes limits the zoonotic potential ofPlasmodium cynomolgi.

    Science.gov (United States)

    Kosaisavee, Varakorn; Suwanarusk, Rossarin; Chua, Adeline C Y; Kyle, Dennis E; Malleret, Benoit; Zhang, Rou; Imwong, Mallika; Imerbsin, Rawiwan; Ubalee, Ratawan; Sámano-Sánchez, Hugo; Yeung, Bryan K S; Ong, Jessica J Y; Lombardini, Eric; Nosten, François; Tan, Kevin S W; Bifani, Pablo; Snounou, Georges; Rénia, Laurent; Russell, Bruce

    2017-09-14

    Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi , can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi -infected human reticulocytes that are strikingly similar to those observed for P vivax These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.

  15. Strictly convex renormings

    Czech Academy of Sciences Publication Activity Database

    Moltó, A.; Orihuela, J.; Troyanski, S.; Zizler, Václav

    2007-01-01

    Roč. 75, č. 3 (2007), s. 647-658 ISSN 0024-6107 R&D Projects: GA AV ČR IAA100190502 Institutional research plan: CEZ:AV0Z10190503 Keywords : strictly convex norms * lattice norm * quasi-diagonal sets Subject RIV: BA - General Mathematics Impact factor: 0.733, year: 2007

  16. Quine's "Strictly Vegetarian" Analyticity

    NARCIS (Netherlands)

    Decock, L.B.

    2017-01-01

    I analyze Quine’s later writings on analyticity from a linguistic point of view. In Word and Object Quine made room for a “strictly vegetarian” notion of analyticity. In later years, he developed this notion into two more precise notions, which I have coined “stimulus analyticity” and “behaviorist

  17. Can plant viruses cross the kingdom border and be pathogenic to humans?

    Science.gov (United States)

    Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

    2015-04-20

    Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans.

  18. Pathogens' toolbox to manipulate human complement.

    Science.gov (United States)

    Fernández, Francisco J; Gómez, Sara; Vega, M Cristina

    2017-12-14

    The surveillance and pathogen fighting functions of the complement system have evolved to protect mammals from life-threatening infections. In turn, pathogens have developed complex molecular mechanisms to subvert, divert and evade the effector functions of the complement. The study of complement immunoevasion by pathogens sheds light on their infection drivers, knowledge that is essential to implement therapies. At the same time, complement evasion also acts as a discovery ground that reveals important aspects of how complement works under physiological conditions. In recent years, complex interrelationships between infection insults and the onset of autoimmune and complement dysregulation diseases have led to propose that encounters with pathogens can act as triggering factors for disease. The correct management of these diseases involves the recognition of their triggering factors and the development and administration of complement-associated molecular therapies. Even more recently, unsuspected proteins from pathogens have been shown to possess moonlighting functions as virulence factors, raising the possibility that behind the first line of virulence factors there be many more pathogen proteins playing secondary, helping and supporting roles for the pathogen to successfully establish infections. In an era where antibiotics have a progressively reduced effect on the management and control of infectious diseases worldwide, knowledge on the mechanisms of pathogenic invasion and evasion look more necessary and pressing than ever. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Functional Metagenomics of Spacecraft Assembly Cleanrooms: Presence of Virulence Factors Associated with Human Pathogens

    OpenAIRE

    Bashir, Mina; Ahmed, Mahjabeen; Weinmaier, Thomas; Ciobanu, Doina; Ivanova, Natalia; Pieber, Thomas R.; Vaishampayan, Parag A.

    2016-01-01

    Strict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during ...

  20. Functional metagenomics of spacecraft assembly cleanrooms: Presence of virulence factors associated with human pathogens.

    OpenAIRE

    Mina Bashir; Mina Bashir; Mahjabeen Ahmed; Mahjabeen Ahmed; Thomas Weinmaier; Doina Ciobanu; Natalia Ivanova; Thomas Pieber; Parag A. Vaishampayan

    2016-01-01

    Strict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during ...

  1. Prediction of molecular mimicry candidates in human pathogenic bacteria.

    Science.gov (United States)

    Doxey, Andrew C; McConkey, Brendan J

    2013-08-15

    Molecular mimicry of host proteins is a common strategy adopted by bacterial pathogens to interfere with and exploit host processes. Despite the availability of pathogen genomes, few studies have attempted to predict virulence-associated mimicry relationships directly from genomic sequences. Here, we analyzed the proteomes of 62 pathogenic and 66 non-pathogenic bacterial species, and screened for the top pathogen-specific or pathogen-enriched sequence similarities to human proteins. The screen identified approximately 100 potential mimicry relationships including well-characterized examples among the top-scoring hits (e.g., RalF, internalin, yopH, and others), with about 1/3 of predicted relationships supported by existing literature. Examination of homology to virulence factors, statistically enriched functions, and comparison with literature indicated that the detected mimics target key host structures (e.g., extracellular matrix, ECM) and pathways (e.g., cell adhesion, lipid metabolism, and immune signaling). The top-scoring and most widespread mimicry pattern detected among pathogens consisted of elevated sequence similarities to ECM proteins including collagens and leucine-rich repeat proteins. Unexpectedly, analysis of the pathogen counterparts of these proteins revealed that they have evolved independently in different species of bacterial pathogens from separate repeat amplifications. Thus, our analysis provides evidence for two classes of mimics: complex proteins such as enzymes that have been acquired by eukaryote-to-pathogen horizontal transfer, and simpler repeat proteins that have independently evolved to mimic the host ECM. Ultimately, computational detection of pathogen-specific and pathogen-enriched similarities to host proteins provides insights into potentially novel mimicry-mediated virulence mechanisms of pathogenic bacteria.

  2. Pathogens and host immunity in the ancient human oral cavity

    Science.gov (United States)

    Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

    2014-01-01

    Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

  3. [THE IDENTIFICATION AND DIFFERENTIATION OF BACTERIOPHAGES OF HUMAN PATHOGENIC VIBRIO].

    Science.gov (United States)

    Gaevskaia, N E; Kudriakova, T A; Makedonova, L D; Kachkina, G V

    2015-04-01

    The issue of identification and differentiation of large group of bacteriophages of human pathogenic vibrio is still unresolved. In research and practical applied purposes it is important to consider characteristics of bacteriophages for establishing similarity and differences between them. The actual study was carried out to analyze specimens of DNA-containing bacteriophages of pathogenic vibrio. The overwhelming majority of them characterized by complicated type of symmetry--phages with double-helical DNA and also phages with mono-helical DNA structure discovered recently in vibrio. For the first time, the general framework of identification and differentiation of bacteriophages of pathogenic vibrio was developed. This achievement increases possibility to establish species assignment of phages and to compare with phages registered in the database. "The collection of bacteriophages and test-strains of human pathogenic vibrio" (No2010620549 of 24.09.210).

  4. Frequent gene fissions associated with human pathogenic bacteria.

    Science.gov (United States)

    Karamichali, Ioanna; Koumandou, V Lila; Karagouni, Amalia D; Kossida, Sophia

    2014-01-01

    Gene fusion and fission events are important for evolutionary studies and for predicting protein-protein interactions. Previous studies have shown that fusion events always predominate over fission events and, in their majority, they represent singular events throughout evolution. In this project, the role of fusion and fission events in the genome evolution of 104 human bacterial pathogens was studied. 141 protein pairs were identified to be involved in gene fusion or fission events. Surprisingly, we find that, in the species analyzed, gene fissions prevail over fusions. Moreover, while most events appear to have occurred only once in evolution, 23% of the gene fusion and fission events identified are deduced to have occurred independently multiple times. Comparison of the analyzed bacteria with non-pathogenic close relatives indicates that this impressive result is associated with the recent evolutionary history of the human bacterial pathogens, and thus is probably caused by their pathogenic lifestyle. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Hybridization and emergence of virulence in opportunistic human yeast pathogens.

    Science.gov (United States)

    Mixão, Verónica; Gabaldón, Toni

    2018-01-01

    Hybridization between different species can result in the emergence of new lineages and adaptive phenotypes. Occasionally, hybridization in fungal organisms can drive the appearance of opportunistic lifestyles or shifts to new hosts, resulting in the emergence of novel pathogens. In recent years, an increasing number of studies have documented the existence of hybrids in diverse yeast clades, including some comprising human pathogens. Comparative and population genomics studies performed on these clades are enabling us to understand what roles hybridization may play in the evolution and emergence of a virulence potential towards humans. Here we survey recent genomic studies on several yeast pathogenic clades where hybrids have been identified, and discuss the broader implications of hybridization in the evolution and emergence of pathogenic lineages. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.

  6. The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants.

    Science.gov (United States)

    Xue, Chaoyang; Tada, Yasuomi; Dong, Xinnian; Heitman, Joseph

    2007-06-14

    Cryptococcus is a globally distributed human fungal pathogen that primarily afflicts immunocompromised individuals. How and why this human fungal pathogen associates with plants and how this environmental niche influences its life cycle remains a mystery. We established Cryptococcus-Arabidopsis and Cryptococcus-Eucalyptus systems and discovered that Cryptococcus proliferates and mates on plant surfaces. Mating efficiency of C. gattii was markedly enhanced on plants and myo-inositol and indole acetic acid were specific plant products that stimulated mating. On Arabidopsis, dwarfing and chlorosis were observed following infection with a fungal mixture of two opposite mating-type strains, but not with either mating-type alone. This infection process is countered by the plant jasmonate-mediated defense mechanism. These findings reveal that Cryptococcus can parasitically interact with plants to complete its sexual cycle, which may impact an understanding of the origin and evolution of both plant and animal fungal pathogens in nature.

  7. Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.

    Directory of Open Access Journals (Sweden)

    Kirsten E Wiens

    Full Text Available The HLA (human leukocyte antigen molecules that present pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many pathogens such as HIV evolve epitope variants in order to evade immune recognition. In contrast, another persistent human pathogen, Mycobacterium tuberculosis, has highly conserved epitope sequences. This raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To address this question, we compared the in silico HLA binding promiscuity of T cell epitopes from pathogens with distinct infection strategies and outcomes of human exposure.We used computer algorithms to predict the binding affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not depend on human hosts for their survival or replication, and their toxin antigens are highly immunogenic human vaccines.We found that B. anthracis and C. tetani epitopes were the most promiscuous of the group that we analyzed. However, there was no consistent difference or trend in promiscuity in epitopes contained in HIV, M. tuberculosis, and S. pyogenes.Our results show that human pathogens with distinct immune evasion strategies and epitope diversities exhibit equivalent levels of T cell epitope promiscuity. These results indicate that differences in epitope promiscuity do not account for the observed differences in epitope variation and conservation.

  8. Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.

    Science.gov (United States)

    Wiens, Kirsten E; Swaminathan, Harish; Copin, Richard; Lun, Desmond S; Ernst, Joel D

    2013-01-01

    The HLA (human leukocyte antigen) molecules that present pathogen-derived epitopes to T cells are highly diverse. Correspondingly, many pathogens such as HIV evolve epitope variants in order to evade immune recognition. In contrast, another persistent human pathogen, Mycobacterium tuberculosis, has highly conserved epitope sequences. This raises the question whether there is also a difference in the ability of these pathogens' epitopes to bind diverse HLA alleles, referred to as an epitope's binding promiscuity. To address this question, we compared the in silico HLA binding promiscuity of T cell epitopes from pathogens with distinct infection strategies and outcomes of human exposure. We used computer algorithms to predict the binding affinity of experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus anthracis and Clostridium tetani toxins, as these bacteria do not depend on human hosts for their survival or replication, and their toxin antigens are highly immunogenic human vaccines. We found that B. anthracis and C. tetani epitopes were the most promiscuous of the group that we analyzed. However, there was no consistent difference or trend in promiscuity in epitopes contained in HIV, M. tuberculosis, and S. pyogenes. Our results show that human pathogens with distinct immune evasion strategies and epitope diversities exhibit equivalent levels of T cell epitope promiscuity. These results indicate that differences in epitope promiscuity do not account for the observed differences in epitope variation and conservation.

  9. Efficient Strictness Analysis of Haskell

    DEFF Research Database (Denmark)

    Jensen, Kristian Damm; Hjæresen, Peter; Rosendahl, Mads

    1994-01-01

    Strictness analysis has been a living field of investigation since Mycroft's original work in 1980, and is getting increasingly significant with the still wider use of lazy functional programming languages. This paper focuses on an actual implementation of a strictness analyser for Haskell...

  10. Waterborne human pathogenic viruses of public health concern.

    Science.gov (United States)

    Ganesh, Atheesha; Lin, Johnson

    2013-12-01

    In recent years, the impending impact of waterborne pathogens on human health has become a growing concern. Drinking water and recreational exposure to polluted water have shown to be linked to viral infections, since viruses are shed in extremely high numbers in the faeces and vomit of infected individuals and are routinely introduced into the water environment. All of the identified pathogenic viruses that pose a significant public health threat in the water environment are transmitted via the faecal-oral route. This group, are collectively known as enteric viruses, and their possible health effects include gastroenteritis, paralysis, meningitis, hepatitis, respiratory illness and diarrhoea. This review addresses both past and recent investigations into viral contamination of surface waters, with emphasis on six types of potential waterborne human pathogenic viruses. In addition, the viral associated illnesses are outlined with reference to their pathogenesis and routes of transmission.

  11. Human pathogens in plant biofilms: Formation, physiology, and detection

    Science.gov (United States)

    Fresh produce, viewed as an essential part of a healthy life style is usually consumed in the form of raw or minimally processed fruits and vegetables, and is a potentially important source of food-borne human pathogenic bacteria and viruses. These are passed on to the consumer since the bacteria ca...

  12. Human pathogenic bacteria as contaminants in freshly consumed vegetables

    NARCIS (Netherlands)

    Waalwijk, C.; Tongeren, van C.A.M.; Zouwen, van der P.S.; Overbeek, van L.S.

    2014-01-01

    The 2011 enterohaemorrhagic Escherichia coli (EHEC) outbreak in Germany casted new light on the potential reservoirs of human pathogenic bacteria (HUPA) other than the ones commonly recognized in animal production chains. Soil, plants and water systems were demonstrated to be environments where HUPA

  13. Natural soil reservoirs for human pathogenic and fecal indicator bacteria

    Science.gov (United States)

    Boschiroli, Maria L; Falkinham, Joseph; Favre-Bonte, Sabine; Nazaret, Sylvie; Piveteau, Pascal; Sadowsky, Michael J.; Byappanahalli, Muruleedhara; Delaquis, Pascal; Hartmann, Alain

    2016-01-01

    Soils receive inputs of human pathogenic and indicator bacteria through land application of animal manures or sewage sludge, and inputs by wildlife. Soil is an extremely heterogeneous substrate and contains meso- and macrofauna that may be reservoirs for bacteria of human health concern. The ability to detect and quantify bacteria of human health concern is important in risk assessments and in evaluating the efficacy of agricultural soil management practices that are protective of crop quality and protective of adjacent water resources. The present chapter describes the distribution of selected Gram-positive and Gram-negative bacteria in soils. Methods for detecting and quantifying soilborne bacteria including extraction, enrichment using immunomagnetic capture, culturing, molecular detection and deep sequencing of metagenomic DNA to detect pathogens are overviewed. Methods for strain phenotypic and genotypic characterization are presented, as well as how comparison with clinical isolates can inform the potential for human health risk.

  14. Comparative genomics and the evolution of pathogenicity in human pathogenic fungi.

    LENUS (Irish Health Repository)

    Moran, Gary P

    2011-01-01

    Because most fungi have evolved to be free-living in the environment and because the infections they cause are usually opportunistic in nature, it is often difficult to identify specific traits that contribute to fungal pathogenesis. In recent years, there has been a surge in the number of sequenced genomes of human fungal pathogens, and comparison of these sequences has proved to be an excellent resource for exploring commonalities and differences in how these species interact with their hosts. In order to survive in the human body, fungi must be able to adapt to new nutrient sources and environmental stresses. Therefore, genes involved in carbohydrate and amino acid metabolism and transport and genes encoding secondary metabolites tend to be overrepresented in pathogenic species (e.g., Aspergillus fumigatus). However, it is clear that human commensal yeast species such as Candida albicans have also evolved a range of specific factors that facilitate direct interaction with host tissues. The evolution of virulence across the human pathogenic fungi has occurred largely through very similar mechanisms. One of the most important mechanisms is gene duplication and the expansion of gene families, particularly in subtelomeric regions. Unlike the case for prokaryotic pathogens, horizontal transfer of genes between species and other genera does not seem to have played a significant role in the evolution of fungal virulence. New sequencing technologies promise the prospect of even greater numbers of genome sequences, facilitating the sequencing of multiple genomes and transcriptomes within individual species, and will undoubtedly contribute to a deeper insight into fungal pathogenesis.

  15. Phosphate Acquisition and Virulence in Human Fungal Pathogens.

    Science.gov (United States)

    Ikeh, Mélanie; Ahmed, Yasmin; Quinn, Janet

    2017-08-22

    The ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. Recent studies in the major human fungal pathogens Candida albicans and Cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for virulence. The phosphate sensing and acquisition pathway in fungi, known as the PHO pathway, has been extensively characterized in the model yeast Saccharomyces cerevisiae . In this review, we highlight recent advances in phosphate sensing and signaling mechanisms, and use the S. cerevisiae PHO pathway as a platform from which to compare the phosphate acquisition and storage strategies employed by several human pathogenic fungi. We also explore the multi-layered roles of phosphate acquisition in promoting fungal stress resistance to pH, cationic, and oxidative stresses, and describe emerging roles for the phosphate storage molecule polyphosphate (polyP). Finally, we summarize the recent studies supporting the necessity of phosphate acquisition in mediating the virulence of human fungal pathogens, highlighting the concept that this requirement is intimately linked to promoting resistance to host-imposed stresses.

  16. Human pathogenic bacteria, fungi, and viruses in Drosophila

    Science.gov (United States)

    Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

    2014-01-01

    Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection. PMID:24398387

  17. Pathogen-Driven Selection in the Human Genome

    Directory of Open Access Journals (Sweden)

    Rachele Cagliani

    2013-01-01

    Full Text Available Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies.

  18. Human herpesvirus 8 – A novel human pathogen

    Directory of Open Access Journals (Sweden)

    Edelman Daniel C

    2005-09-01

    Full Text Available Abstract In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8 1. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.

  19. Species Protection in the European Union : How Strict is Strict?

    NARCIS (Netherlands)

    Schoukens, Hendrik; Bastmeijer, Kees; Born et al., Charles-Hubert

    2015-01-01

    European Union law to protect wild species of plants and animals is generally considered as ‘strict’. Opponents of nature conservation law often pick the species protection components of the EU Bird Directive and Habitat Directive as a prime example of an unnecessary strict regulatory scheme that

  20. Mechanisms of Defense against Intracellular Pathogens Mediated by Human Macrophages.

    Science.gov (United States)

    Bloom, Barry R; Modlin, Robert L

    2016-06-01

    The key question our work has sought to address has been, "What are the necessary and sufficient conditions that engender protection from intracellular pathogens in the human host?" The origins of this work derive from a long-standing interest in the mechanisms of protection against two such paradigmatic intracellular pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, that have brilliantly adapted to the human host. It was obvious that these pathogens, which cause chronic diseases and persist in macrophages, must have acquired subtle strategies to resist host microbicidal mechanisms, yet since the vast majority of individuals infected with M. tuberculosis do not develop disease, there must be some potent human antimicrobial mechanisms. What follows is not a comprehensive review of the vast literature on the role of human macrophages in protection against infectious disease, but a summary of the research in our two laboratories with collaborators that we hope has contributed to some understanding of mechanisms of resistance and pathogenesis. While mouse models revealed some necessary conditions for protection, e.g., innate immunity, Th1 cells and their cytokines, and major histocompatibility complex class I-restricted T cells, here we emphasize multiple antimicrobial mechanisms that exist in human macrophages that differ from those of most experimental animals. Prominent here is the vitamin D-dependent antimicrobial pathway common to human macrophages activated by innate and acquired immune responses, mediated by antimicrobial peptides, e.g., cathelicidin, through an interleukin-15- and interleukin-32-dependent common pathway that is necessary for macrophage killing of M. tuberculosis in vitro.

  1. Probiotic Activity of Saccharomyces cerevisiae var. boulardii Against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Katarzyna Rajkowska

    2012-01-01

    Full Text Available Infectious diarrhoea is associated with a modification of the intestinal microflora and colonization of pathogenic bacteria. Tests were performed for seven probiotic yeast strains of Saccharomyces cerevisiae var. boulardii, designated for the prevention and treatment of diarrhoea. To check their possible effectiveness against diarrhoea of different etiologies, the activity against a variety of human pathogenic or opportunistic bacteria was investigated in vitro. In mixed cultures with S. cerevisiae var. boulardii, a statistically significant reduction was observed in the number of cells of Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus, by even 55.9 % in the case of L. monocytogenes compared with bacterial monocultures. The influence of yeasts was mostly associated with the shortening of the bacterial lag phase duration, more rapid achievement of the maximum growth rates, and a decrease by 4.4–57.1 % (L. monocytogenes, P. aeruginosa, or an increase by 1.4–70.6 % (Escherichia coli, Enterococcus faecalis, Salmonella Typhimurium in the exponential growth rates. Another issue included in the research was the ability of S. cerevisiae var. boulardii to bind pathogenic bacteria to its cell surface. Yeasts have shown binding capacity of E. coli, S. Typhimurium and additionally of S. aureus, Campylobacter jejuni and E. faecalis. However, no adhesion of L. monocytogenes and P. aeruginosa to the yeast cell wall was noted. The probiotic activity of S. cerevisiae var. boulardii against human pathogens is related to a decrease in the number of viable and active cells of bacteria and the binding capacity of yeasts. These processes may limit bacterial invasiveness and prevent bacterial adherence and translocation in the human intestines.

  2. tkt1, located on a novel pathogenicity island, is prevalent in avian and human extraintestinal pathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Li Ganwu

    2012-04-01

    Full Text Available Abstract Background Extraintestinal pathogenic Escherichia coli are important pathogens of human and animal hosts. Some human and avian extraintestinal pathogenic E. coli are indistinguishable on the basis of diseases caused, multilocus sequence and phylogenetic typing, carriage of large virulence plasmids and traits known to be associated with extraintestinal pathogenic E. coli virulence. Results The gene tkt1 identified by a previous signature-tagged transposon mutagenesis study, was found on a 16-kb genomic island of avian pathogenic Escherichia coli (APEC O1, the first pathogenic Escherichia coli strain whose genome has been completely sequenced. tkt1 was present in 39.6% (38/96 of pathogenic Escherichia coli strains, while only 6.25% (3/48 of E. coli from the feces of apparently healthy chickens was positive. Further, tkt1 was predominantly present in extraintestinal pathogenic E. coli belonging to the B2 phylogenetic group, as compared to extraintestinal pathogenic E. coli of other phylogenetic groups. The tkt1-containing genomic island is inserted between the metE and ysgA genes of the E. coli K12 genome. Among different extraintestinal pathogenic E. coli of the B2 phylogenetic group, 61.7% of pathogenic Escherichia coli, 80.6% of human uropathogenic E.coli and 94.1% of human neonatal meningitis-causing E. coli, respectively, harbor a complete copy of this island; whereas, only a few avian fecal E. coli strains contained the complete island. Functional analysis showed that Tkt1 confers very little transketolase activity but is involved in peptide nitrogen metabolism. Conclusion These results suggest tkt1 and its corresponding genomic island are frequently associated with avian and human ExPEC and are involved in bipeptide metabolism.

  3. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Desjardins

    2011-10-01

    Full Text Available Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18 and one strain of Paracoccidioides lutzii (Pb01. These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic

  4. Nucleic acid probes in the diagnosis of human microbial pathogens

    International Nuclear Information System (INIS)

    Hyypia, T.; Huovinen, P.; Holmberg, M.; Pettersson, U.

    1989-01-01

    The development of effective vaccines and antimicrobial drugs against infectious diseases has been among the most successful achievements in modern medicine. The control of these diseases requires efficient diagnostic methods for the evaluation of the prevalence of diseases and for initiation of specific treatment. Virtually all known microbes can be specifically identified today but in many cases further development is needed for more accurate, rapid, easy-to-use, and inexpensive diagnostic assays. Cell culture facilities are needed for the isolation of viruses in clinical specimens. Any gene of any known microorganism can be cloned in a vector and produced in large amounts economically and then used in diagnostic assays for the identification of the pathogen. The application of the nucleic acid hybridization methods in detection of human pathogens has received considerable attention during the past few years. This paper presents examples of this application of gene technology

  5. MOLECULAR BACKGROUND OF FLUOROQUINOLONE RESISTANCE IN PATHOGENIC HUMAN MYCOPLASMAS

    Directory of Open Access Journals (Sweden)

    A. N. Vaganova

    2017-01-01

    Full Text Available Human mycoplasma pathogens are resistant to many types of antibiotics because of the lack of a cell wall. Macrolides are most often used for the treatment of mycoplasmosis, but the spread of forms resistant to these antibiotics requires the use of alternative treatment regimens, in particular, the administration of f luoroquinolones and tetracyclines. Of the existing antimicrobial compounds, only f luoroquinolones have a bactericidal effect against mycoplasmas, so use of these antimicrobials is preferable for the treatment of immunosuppressed patients. The limitation of the f luoroquinolones is the resistance of the causative agent to these antimicrobials. Mutations leading to amino acid substitutions in the composition of the targets of f luoroquinolones, gyrase and topoisomerase IV are the most common cause of resistance to f luoroquinolones both in mycoplasms and in other bacteria. It was noted that for mycoplasmas belonging to different species have different patterns of substitutions in the subunits of gyrase and topoisomerase IV. The differences of the structure of these proteins, ref lected in the natural susceptibility to f luoroquinolones in mycoplasmas, may be a reason of this heterogeneity. A number of studies indicate the existence of additional resistance mechanisms, which, first of all, include multiple-resistance systems. Such systems belonging to the ABC-transporter group were also found in mycoplasmas. They are described in Mycoplasma hominis and M. pneumoniae, in M. hominis, their ability to excrete f luoroquinolones from the cells was observed, and in M. pneumoniae the ability of multiple-resistance systems to export macrolides also was noted. Genes encoding components of multiple resistance systems have been found in genomes of other species, including M. genitalium and mycoplasmas, causing animal diseases. Also, in the non-pathogenic for human mycoplasmas Acholeplasma laidlawii, the ability to export proteins and genetic

  6. Molecular Basis of Latency in Pathogenic Human Viruses

    Science.gov (United States)

    Garcia-Blanco, Mariano A.; Cullen, Bryan R.

    1991-11-01

    Several human viruses are able to latently infect specific target cell populations in vivo. Analysis of the replication cycles of herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus suggests that the latent infections established by these human pathogens primarily result from a lack of host factors critical for the expression of viral early gene products. The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of these viral regulatory proteins and lead to a burst of lytic viral replication. Latency in these eukaryotic viruses therefore contrasts with latency in bacteriophage, which is maintained primarily by the expression of virally encoded repressors of lytic replication.

  7. Human pathogens in plant biofilms: Formation, physiology, and detection.

    Science.gov (United States)

    Ximenes, Eduardo; Hoagland, Lori; Ku, Seockmo; Li, Xuan; Ladisch, Michael

    2017-07-01

    Fresh produce, viewed as an essential part of a healthy life style is usually consumed in the form of raw or minimally processed fruits and vegetables, and is a potentially important source of food-borne human pathogenic bacteria and viruses. These are passed on to the consumer since the bacteria can form biofilms or otherwise populate plant tissues, thereby using plants as vectors to infect animal hosts. The life cycle of the bacteria in plants differs from those in animals or humans and results in altered physiochemical and biological properties (e.g., physiology, immunity, native microflora, physical barriers, mobility, and temperature). Mechanisms by which healthy plants may become contaminated by microorganisms, develop biofilms, and then pass on their pathogenic burden to people are explored in the context of hollow fiber microfiltration by which plant-derived microorganisms may be recovered and rapidly concentrated to facilitate study of their properties. Enzymes, when added to macerated plant tissues, hydrolyze or alter macromolecules that would otherwise foul hollow-fiber microfiltration membranes. Hence, microfiltration may be used to quickly increase the concentration of microorganisms to detectable levels. This review discusses microbial colonization of vegetables, formation and properties of biofilms, and how hollow fiber microfiltration may be used to concentrate microbial targets to detectable levels. The use of added enzymes helps to disintegrate biofilms and minimize hollow fiber membrane fouling, thereby providing a new tool for more time effectively elucidating mechanisms by which biofilms develop and plant tissue becomes contaminated with human pathogens. Biotechnol. Bioeng. 2017;114: 1403-1418. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Pathogens and host immunity in the ancient human oral cavity

    DEFF Research Database (Denmark)

    Warinner, Christina; Rodrigues, João F Matias; Vyas, Rounak

    2014-01-01

    cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction......Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral...

  9. Strictness Analysis for Attribute Grammars

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    1992-01-01

    interpretation of attribute grammars. The framework is used to construct a strictness analysis for attribute grammars. Results of the analysis enable us to transform an attribute grammar such that attributes are evaluated during parsing, if possible. The analysis is proved correct by relating it to a fixpoint...... semantics for attribute grammars. An implementation of the analysis is discussed and some extensions to the analysis are mentioned....

  10. Standardized metadata for human pathogen/vector genomic sequences.

    Directory of Open Access Journals (Sweden)

    Vivien G Dugan

    Full Text Available High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs, the Bioinformatics Resource Centers (BRCs for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID, part of the National Institutes of Health (NIH, informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium's minimal information (MIxS and NCBI's BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI. The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will

  11. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Science.gov (United States)

    da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  12. Genetics of Candida albicans, a diploid human fungal pathogen.

    Science.gov (United States)

    Noble, Suzanne M; Johnson, Alexander D

    2007-01-01

    Candida albicans is a species of fungus that typically resides in the gastrointestinal tracts of humans and other warm-blooded animals. It is also the most common human fungal pathogen, causing a variety of skin and soft tissue infections in healthy people and more virulent invasive and disseminated diseases in patients with compromised immune systems. How this microorganism manages to persist in healthy hosts but also to cause a spectrum of disease states in the immunocompromised host are questions of significant biological interest as well as major clinical and economic importance. In this review, we describe recent developments in population genetics, the mating process, and gene disruption technology that are providing much needed experimental insights into the biology of C. albicans.

  13. Appraisal of Microbial Evolution to Commensalism and Pathogenicity in Humans

    Directory of Open Access Journals (Sweden)

    Asit Ranjan Ghosh

    2013-01-01

    Full Text Available The human body is host to a number of microbes occurring in various forms of host-microbe associations, such as commensals, mutualists, pathogens and opportunistic symbionts. While this association with microbes in certain cases is beneficial to the host, in many other cases it seems to offer no evident benefit or motive. The emergence and re-emergence of newer varieties of infectious diseases with causative agents being strains that were once living in the human system makes it necessary to study the environment and the dynamics under which this host microbe relationship thrives. The present discussion examines this interaction while tracing the origins of this association, and attempts to hypothesize a possible framework of selective pressures that could have lead microbes to inhabit mammalian host systems.

  14. Drosophila as a genetic model for studying pathogenic human viruses.

    Science.gov (United States)

    Hughes, Tamara T; Allen, Amanda L; Bardin, Joseph E; Christian, Megan N; Daimon, Kansei; Dozier, Kelsey D; Hansen, Caom L; Holcomb, Lisa M; Ahlander, Joseph

    2012-02-05

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Flexible or Strict Taxonomic Organization?

    DEFF Research Database (Denmark)

    Glückstad, Fumiko Kano; Mørup, Morten

    2012-01-01

    This work compares methods for constructing feature-based ontologies that are supposed to be used for culturally-specific knowledge transfer. The methods to be compared are the Terminological Ontology (TO) [1], a method of constructing ontology based on strict principles and rules, and the Infinite...... Relational Model (IRM) [2], a novel unsupervised machine learning method that learns multi-dimensional relations among concepts and features from loosely structured datasets. These methods are combined with a novel cognitive model, the Bayesian Model of Generalization (BMG) [3] that maps culturally...

  16. Preliminary molecular characterization of the human pathogen Angiostrongylus cantonensis

    Directory of Open Access Journals (Sweden)

    He Ai

    2009-10-01

    Full Text Available Abstract Background Human angiostrongyliasis is an emerging food-borne public health problem, with the number of cases increasing worldwide, especially in mainland China. Angiostrongylus cantonensis is the causative agent of this severe disease. However, little is known about the genetics and basic biology of A. cantonensis. Results A cDNA library of A. cantonensis fourth-stage larvae was constructed, and ~1,200 clones were sequenced. Bioinformatic analyses revealed 378 cDNA clusters, 54.2% of which matched known genes at a cutoff expectation value of 10-20. Of these 378 unique cDNAs, 168 contained open reading frames encoding proteins containing an average of 238 amino acids. Characterization of the functions of these encoded proteins by Gene Ontology analysis showed enrichment in proteins with binding and catalytic activity. The observed pattern of enzymes involved in protein metabolism, lipid metabolism and glycolysis may reflect the central nervous system habitat of this pathogen. Four proteins were tested for their immunogenicity using enzyme-linked immunosorbent assays and histopathological examinations. The specificity of each of the four proteins was superior to that of crude somatic and excretory/secretory antigens of larvae, although their sensitivity was relatively low. We further showed that mice immunized with recombinant cystatin, a product of one of the four cDNA candidate genes, were partially protected from A. cantonensis infection. Conclusion The data presented here substantially expand the available genetic information about the human pathogen A. cantonensis, and should be a significant resource for angiostrongyliasis researchers. As such, this work serves as a starting point for molecular approaches for diagnosing and controlling human angiostrongyliasis.

  17. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter.

    Science.gov (United States)

    Colles, Frances M; Cain, Russell J; Nickson, Thomas; Smith, Adrian L; Roberts, Stephen J; Maiden, Martin C J; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-13

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the 'optical flow' patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7-10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. © 2016 The Authors.

  18. Human Pathogens on Plants: Designing a Multidisciplinary Strategy for Research.

    Science.gov (United States)

    Fletcher, Jacqueline; Leach, Jan E; Eversole, Kellye; Tauxe, Robert

    2014-10-15

    Recent efforts to address concerns about microbial contamination of food plants and resulting foodborne illness have prompted new collaboration and interactions between the scientific communities of plant pathology and food safety. This article provides perspectives from scientists of both disciplines and presents selected research results and concepts that highlight existing and possible future synergisms for audiences of both disciplines. Plant pathology is a complex discipline that encompasses studies of the dissemination, colonization, and infection of plants by microbes such as bacteria, viruses, fungi, and oomycetes. Plant pathologists study plant diseases as well as host plant defense responses and disease management strategies with the goal of minimizing disease occurrences and impacts. Repeated outbreaks of human illness attributed to the contamination of fresh produce, nuts and seeds, and other plant-derived foods by human enteric pathogens such as Shiga toxin-producing Escherichia coli and Salmonella spp. have led some plant pathologists to broaden the application of their science in the past two decades, to address problems of human pathogens on plants (HPOPs). Food microbiology, which began with the study of microbes that spoil foods and those that are critical to produce food, now also focuses study on how foods become contaminated with pathogens and how this can be controlled or prevented. Thus, at the same time, public health researchers and food microbiologists have become more concerned about plant-microbe interactions before and after harvest. New collaborations are forming between members of the plant pathology and food safety communities, leading to enhanced research capacity and greater understanding of the issues for which research is needed. The two communities use somewhat different vocabularies and conceptual models. For example, traditional plant pathology concepts such as the disease triangle and the disease cycle can help to define

  19. The graphene oxide contradictory effects against human pathogens.

    Science.gov (United States)

    Palmieri, Valentina; Carmela Lauriola, Maria; Ciasca, Gabriele; Conti, Claudio; De Spirito, Marco; Papi, Massimiliano

    2017-04-18

    Standing out as the new wonder bidimensional material, graphene oxide (GO) has aroused an exceptional interest in biomedical research by holding promise for being the antibacterial of future. First, GO possesses a specific interaction with microorganisms combined with a mild toxicity for human cells. Additionally, its antibacterial action seems to be directed to multiple targets in pathogens, causing both membranes mechanical injury and oxidative stress. Lastly, compared to other carbon materials, GO has easy and low-cost processing and is environment-friendly. This remarkable specificity and multi-targeting antibacterial activity come at a time when antibiotic resistance represents the major health challenge. Unfortunately, a comprehensive framework to understand how to effectively utilize this material against microorganisms is still lacking. In the last decade, several groups tried to define the mechanisms of interaction between GO flakes and pathogens but conflicting results have been reported. This review is focused on all the contradictions of GO antimicrobial properties in solution. Flake size, incubation protocol, time of exposure and species considered are examples of factors influencing results. These parameters will be summarized and analyzed with the aim of defining the causes of contradictions, to allow fast GO clinical application.

  20. The graphene oxide contradictory effects against human pathogens

    Science.gov (United States)

    Palmieri, Valentina; Carmela Lauriola, Maria; Ciasca, Gabriele; Conti, Claudio; De Spirito, Marco; Papi, Massimiliano

    2017-04-01

    Standing out as the new wonder bidimensional material, graphene oxide (GO) has aroused an exceptional interest in biomedical research by holding promise for being the antibacterial of future. First, GO possesses a specific interaction with microorganisms combined with a mild toxicity for human cells. Additionally, its antibacterial action seems to be directed to multiple targets in pathogens, causing both membranes mechanical injury and oxidative stress. Lastly, compared to other carbon materials, GO has easy and low-cost processing and is environment-friendly. This remarkable specificity and multi-targeting antibacterial activity come at a time when antibiotic resistance represents the major health challenge. Unfortunately, a comprehensive framework to understand how to effectively utilize this material against microorganisms is still lacking. In the last decade, several groups tried to define the mechanisms of interaction between GO flakes and pathogens but conflicting results have been reported. This review is focused on all the contradictions of GO antimicrobial properties in solution. Flake size, incubation protocol, time of exposure and species considered are examples of factors influencing results. These parameters will be summarized and analyzed with the aim of defining the causes of contradictions, to allow fast GO clinical application.

  1. Phytomonas serpens: immunological similarities with the human trypanosomatid pathogens.

    Science.gov (United States)

    Santos, André L S; d'Avila-Levy, Claudia M; Elias, Camila G R; Vermelho, Alane B; Branquinha, Marta H

    2007-07-01

    The present review provides an overview of recent discoveries concerning the immunological similarities between Phytomonas serpens, a tomato parasite, and human trypanosomatid pathogens, with special emphasis on peptidases. Leishmania spp. and Trypanosoma cruzi express peptidases that are well-known virulence factors, named leishmanolysin and cruzipain. P. serpens synthesizes two distinct classes of proteolytic enzymes, metallo- and cysteine-type peptidases, that share common epitopes with leishmanolysin and cruzipain, respectively. The leishmanolysin-like and cruzipain-like molecules from P. serpens participate in several biological processes including cellular growth and adhesion to the salivary glands of Oncopeltus fasciatus, a phytophagous insect experimental model. Since previous reports demonstrated that immunization of mice with P. serpens induced a partial protective immune response against T. cruzi, this plant trypanosomatid may be a suitable candidate for vaccine studies. Moreover, comparative approaches in the Trypanosomatidae family may be useful to understand kinetoplastid biology, biochemistry and evolution.

  2. Cell wall integrity signalling in human pathogenic fungi.

    Science.gov (United States)

    Dichtl, Karl; Samantaray, Sweta; Wagener, Johannes

    2016-09-01

    Fungi are surrounded by a rigid structure, the fungal cell wall. Its plasticity and composition depend on active regulation of the underlying biosynthesis and restructuring processes. This involves specialised signalling pathways that control gene expression and activities of biosynthetic enzymes. The cell wall integrity (CWI) pathway is the central signalling cascade required for the adaptation to a wide spectrum of cell wall perturbing conditions, including heat, oxidative stress and antifungals. In the recent years, great efforts were made to analyse the CWI pathway of diverse fungi. It turned out that the CWI signalling cascade is mostly conserved in the fungal kingdom. In this review, we summarise as well as compare the current knowledge on the canonical CWI pathway in the human pathogenic fungi Candida albicans, Candida glabrata, Aspergillus fumigatus and Cryptococcus neoformans. Understanding the differences and similarities in the stress responses of these organisms could become a key to improving existing or developing new antifungal therapies. © 2016 John Wiley & Sons Ltd.

  3. Interrelationships of food safety and plant pathology: the life cycle of human pathogens on plants.

    Science.gov (United States)

    Barak, Jeri D; Schroeder, Brenda K

    2012-01-01

    Bacterial food-borne pathogens use plants as vectors between animal hosts, all the while following the life cycle script of plant-associated bacteria. Similar to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain pathogens have a foothold in agricultural production areas. The commonality of environmental contamination translates to contact with plants. Because of the chronic absence of kill steps against human pathogens for fresh produce, arrival on plants leads to persistence and the risk of human illness. Significant research progress is revealing mechanisms used by human pathogens to colonize plants and important biological interactions between and among bacteria in planta. These findings articulate the difficulty of eliminating or reducing the pathogen from plants. The plant itself may be an untapped key to clean produce. This review highlights the life of human pathogens outside an animal host, focusing on the role of plants, and illustrates areas that are ripe for future investigation.

  4. A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe

    Science.gov (United States)

    McIntyre, K. Marie; Setzkorn, Christian; Hepworth, Philip J.; Morand, Serge; Morse, Andrew P.; Baylis, Matthew

    2014-01-01

    Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. PMID:25136810

  5. 76 FR 30176 - Expedited Review for New Animal Drug Applications for Human Pathogen Reduction Claims; Withdrawal...

    Science.gov (United States)

    2011-05-24

    ... HUMAN SERVICES Food and Drug Administration (Formerly Docket No. 2001D-0107) Expedited Review for New Animal Drug Applications for Human Pathogen Reduction Claims; Withdrawal of Guidance AGENCY: Food and... guidance for industry 121 entitled ``Expedited Review for New Animal Drug Applications for Human Pathogen...

  6. Draft genome sequence of the first human isolate of the ruminant pathogen Mycoplasma capricolum subsp. capricolum

    DEFF Research Database (Denmark)

    Seersholm, Frederik Valeur; Fischer, Anne; Heller, Martin

    2015-01-01

    Mycoplasma capricolum subsp. capricolum is a well-known pathogen of small ruminants. A recent human case of septicemia involving this agent raised the question of its potential pathogenicity to humans. We present the first draft genome sequence of a human Mycoplasma capricolum subsp. capricolum...

  7. Purine Acquisition and Synthesis by Human Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Jessica L. Chitty

    2017-06-01

    Full Text Available While members of the Kingdom Fungi are found across many of the world’s most hostile environments, only a limited number of species can thrive within the human host. The causative agents of the most common invasive fungal infections are Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. During the infection process, these fungi must not only combat the host immune system while adapting to dramatic changes in temperature and pH, but also acquire sufficient nutrients to enable growth and dissemination in the host. One class of nutrients required by fungi, which is found in varying concentrations in their environmental niches and the human host, is the purines. These nitrogen-containing heterocycles are one of the most abundant organic molecules in nature and are required for roles as diverse as signal transduction, energy metabolism and DNA synthesis. The most common life-threatening fungal pathogens can degrade, salvage and synthesize de novo purines through a number of enzymatic steps that are conserved. While these enable them to adapt to the changing purine availability in the environment, only de novo purine biosynthesis is essential during infection and therefore an attractive antimycotic target.

  8. Antimicrobial properties of marine seaweed, Sargassum muticum against human pathogens

    Directory of Open Access Journals (Sweden)

    Puthamohan Vinayaga Moorthi

    2015-02-01

    Full Text Available Objective: To evaluate the antibacterial efficiency of the seaweed, Sargassum muticum (S. muticum collected from Pudumadam, Ramanathapuram, Tamil Nadu, India. Methods: Crude solvent extracts of S. muticum were obtained by using Soxhlet extraction and the solvents like acetone, methanol and chloroform. These different extracts were tested against different human bacterial pathogens such as Micrococcus sp., Staphylococcus aureus (methicillin resistance, Salmonella paratyphi B, Staphylococcus epidermis (3615, Enterobacter aerogenus (111, Klebsiella pneumonia (109, Shigella fleschneri (1457 (S. fleschneri, Proteus vulgaris (1771, Staphylococcus aureus (96 and Salmonella typhymurium (SP7 which were obtained from Microbial Type Culture Collection, Indian Institute of Microbial Technology, Chandigarh, India. Results: The results revealed that acetone extract had unveiled the maximum of 11 mm zone of inhibition at 40 µL against S. fleschneri. Similar zone of inhibition (11 mm was also observed at 50 µL against Micrococcus sp. and S. fleschneri. Followed by acetone extract, chloroform extract also contributed 11 mm zone of inhibition against S. fleschneri and Salmonella paratyphi B at 40 and 50 µL respectively. Besides, methanol extracts revealed meager antibacterial activity (9 mm. Conclusions: The present investigation suggests that the phytochemical constituent of the S. muticum might be suitable agents for the control of human deadly diseases.

  9. Genotype-specific pathogenic effects in human dilated cardiomyopathy.

    Science.gov (United States)

    Bollen, Ilse A E; Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W; Pinto, Jose R; Krüger, Martina; Kuster, Diederik W D; van der Velden, Jolanda

    2017-07-15

    Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3 p.98trunc resulted in haploinsufficiency, increased Ca 2+ -sensitivity and reduced length-dependent activation. TNNT2 p.K217del caused increased passive tension. A mutation in the gene encoding Lamin A/C (LMNA p.R331Q ) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy. Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM-causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3 p.98truncation ) and cardiac troponin T (TNNT2 p.K217deletion ; also known as the p.K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNA p.R331Q ). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3 p.98trunc and TNNT2 p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3 p.98trunc showed pure haploinsufficiency, increased Ca 2+ -sensitivity and impaired length-dependent activation. The TNNT2 p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild-type troponin complex corrected troponin protein levels to 83% of controls in the TNNI3

  10. Genotype‐specific pathogenic effects in human dilated cardiomyopathy

    Science.gov (United States)

    Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W.; Pinto, Jose R.; Krüger, Martina; Kuster, Diederik W. D.; van der Velden, Jolanda

    2017-01-01

    Key points Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3p.98trunc resulted in haploinsufficiency, increased Ca2+‐sensitivity and reduced length‐dependent activation. TNNT2p.K217del caused increased passive tension.A mutation in the gene encoding Lamin A/C (LMNA p.R331Q) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy.Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Abstract Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non‐sarcomeric genes. In this study we defined the pathogenic effects of three DCM‐causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation) and cardiac troponin T (TNNT2p.K217deletion; also known as the p.K210del) and the non‐sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane‐permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3p.98trunc and TNNT2p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3p.98trunc showed pure haploinsufficiency, increased Ca2+‐sensitivity and impaired length‐dependent activation. The TNNT2p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild‐type troponin complex corrected troponin protein levels to 83% of

  11. Genetic Dissection of the Host Tropism of Human-Tropic Pathogens.

    Science.gov (United States)

    Douam, Florian; Gaska, Jenna M; Winer, Benjamin Y; Ding, Qiang; von Schaewen, Markus; Ploss, Alexander

    2015-01-01

    Infectious diseases are the second leading cause of death worldwide. Although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. Hence, uncovering the genetic basis underlying the narrow tropism of such pathogens is critical for understanding their mechanisms of infection and pathogenesis. Moreover, such genetic dissection is essential for the generation of permissive animal models that can serve as critical tools for the development of therapeutics or vaccines against challenging human pathogens. In this review, we describe different experimental approaches utilized to uncover the genetic foundation regulating pathogen host tropism as well as their relevance for studying the tropism of several important human pathogens. Finally, we discuss the current and future uses of this knowledge for generating genetically modified animal models permissive for these pathogens.

  12. The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Matthew D Dyer

    2010-08-01

    Full Text Available Bacillus anthracis, Francisella tularensis, and Yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as NIAID Category A priority pathogens for possible use as biological weapons. However, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion.In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions between human proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, we identified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactions including interactions involving 304 B. anthracis, 52 F. tularensis, and 330 Y. pestis proteins that are uncharacterized. Computational analysis revealed that pathogen proteins preferentially interact with human proteins that are hubs and bottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conserved amongst the three networks. Functionally, such conserved modules reveal commonalities between how the different pathogens interact with crucial host pathways involved in inflammation and immunity.These data constitute the first extensive protein interaction networks constructed for bacterial pathogens and their human hosts. This study provides novel insights into host-pathogen interactions.

  13. Comparison of extraintestinal pathogenic Escherichia coli strains from human and avian sources reveals a mixed subset representing potential zoonotic pathogens

    NARCIS (Netherlands)

    Johnson, Timothy J.; Wannemuehler, Yvonne; Johnson, Sara J.; Stell, Adam L.; Doetkott, Curt; Johnson, James R.; Kim, Kwang S.; Spanjaard, Lodewijk; Nolan, Lisa K.

    2008-01-01

    Since extraintestinal pathogenic Escherichia coli (ExPEC) strains from human and avian hosts encounter similar challenges in establishing infection in extraintestinal locations, they may share similar contents of virulence genes and capacities to cause disease. In the present study, 1,074 ExPEC

  14. Antibacterial activity of some medicinal plants against selected human pathogenic bacteria

    OpenAIRE

    Khan, Usman Ali; Rahman, Hazir; Niaz, Zeeshan; Qasim, Muhammad; Khan, Jafar; Tayyaba,; Rehman, Bushra

    2013-01-01

    Medicinal plants are traditionally used for the treatment of human infections. The present study was undertaken to investigate Bergenia ciliata, Jasminum officinale, and Santalum album for their potential activity against human bacterial pathogens.

  15. An unclassified microorganism: novel pathogen candidate lurking in human airways.

    Directory of Open Access Journals (Sweden)

    Kazumasa Fukuda

    Full Text Available During the assessments of the correlation of the diseases and the microbiota of various clinical specimens, unique 16S ribosomal RNA (rRNA gene sequences (less than 80% similarity to known bacterial type strains were predominantly detected in a bronchoalveolar lavage fluid (BALF specimen from a patient with chronic lower respiratory tract infection. The origin of this unique sequence is suspected to be the causative agent of the infection. We temporarily named the owner organism of this sequence "IOLA" (Infectious Organism Lurking in Airways. In order to evaluate the significance of IOLA in human lung disorders, we performed several experiments. IOLA-16S rRNA genes were detected in 6 of 386 clone libraries constructed from clinical specimens of patients with respiratory diseases (in our study series. The gene sequences (1,427 bp are identical, and no significantly similar sequence was found in public databases (using NCBI blastn except for the 8 shorter sequences detected from patients with respiratory diseases in other studies from 2 other countries. Phylogenetic analyses revealed that the 16S rRNA gene of IOLA is more closely related to eukaryotic mitochondria than bacteria. However, the size and shape of IOLA seen by fluorescent in-situ hybridization are similar to small bacteria (approximately 1 µm with a spherical shape. Furthermore, features of both bacteria and mitochondria were observed in the genomic fragment (about 19 kb of IOLA, and the GC ratio of the sequence was extremely low (20.5%. Two main conclusions were reached: (1 IOLA is a novel bacteria-like microorganism that, interestingly, possesses features of eukaryotic mitochondria. (2 IOLA is a novel pathogen candidate, and it may be the causative agent of human lung or airway disease. IOLA exists in BALF specimens from patients with remarkable symptoms; this information is an important piece for helping solve the elusive etiology of chronic respiratory disorders.

  16. Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens

    OpenAIRE

    Wessels, Michael; Holden, Matthew; Heather, Zoe; Paillot, Romain; Steward, Karen; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie; Holroyd, Nancy; Mungall, Karen; Quail, Michael; Sanders, Mandy; Simmonds, Mark; Willey, David

    2009-01-01

    The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Strepto...

  17. Antagonistic activity of antibiotic producing Streptomyces sp. against fish and human pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Nazmul Hossain

    2014-04-01

    Full Text Available In this study, attempts were made to isolate Streptomyces sp. from soil samples of two different regions of Bangladesh and evaluate their antagonistic activity against fish and human pathogenic bacteria. A total of 10 isolates were identified as Streptomyces sp. based on several morphological, physiological and biochemical tests. Cross streak method was used to observe the antagonistic activity of the Streptomyces sp. isolates against different fish pathogens belonging to the genus Aeromonas, Pseudomonas and Edwardsiella and human clinical isolates belonging to the genus Klebsiella, Salmonella and Streptococcus. Seven Streptomyces sp. isolates showed antagonism against both fish and human pathogenic bacteria. Four isolates viz., N24, N26, N28 and N47 showed broad spectrum of antagonistic activity (80-100% against all genera of fish and human pathogenic bacteria. The isolate N49 exhibited highest spectrum of antagonism against all fish pathogens (90-100% but comparatively lower degree of antagonism against human pathogens (50-60%. Rest of the two isolates (N21 and N23 showed variability in their antagonism. Results showed that broad spectrum antibiotic(s could be developed from the isolates N24, N26, N28 and N47against several human and fish pathogens. The isolate N49 could be a potential source of antibiotic, especially for fish pathogenic bacteria.

  18. Developmental gene expression profiles of the human pathogen Schistosoma japonicum

    Directory of Open Access Journals (Sweden)

    McManus Donald P

    2009-03-01

    Full Text Available Abstract Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae, juvenile (lung schistosomula and paired but pre-egg laying adults and adult (paired, mature males and egg-producing females, both examined separately. Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.

  19. Genome Sequence of the Human Pathogen Vibrio cholerae Amazonia

    Science.gov (United States)

    Thompson, Cristiane C.; Marin, Michel A.; Dias, Graciela M.; Dutilh, Bas E.; Edwards, Robert A.; Iida, Tetsuya; Thompson, Fabiano L.; Vicente, Ana Carolina P.

    2011-01-01

    Vibrio cholerae O1 Amazonia is a pathogen that was isolated from cholera-like diarrhea cases in at least two countries, Brazil and Ghana. Based on multilocus sequence analysis, this lineage belongs to a distinct profile compared to strains from El Tor and classical biotypes. The genomic analysis revealed that it contains Vibrio pathogenicity island 2 and a set of genes related to pathogenesis and fitness, such as the type VI secretion system, present in choleragenic V. cholerae strains. PMID:21952545

  20. The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease.

    Science.gov (United States)

    Pearce-Duvet, Jessica M C

    2006-08-01

    Many significant diseases of human civilization are thought to have arisen concurrently with the advent of agriculture in human society. It has been hypothesised that the food produced by farming increased population sizes to allow the maintenance of virulent pathogens, i.e. civilization pathogens, while domestic animals provided sources of disease to humans. To determine the relationship between pathogens in humans and domestic animals, I examined phylogenetic data for several human pathogens that are commonly evolutionarily linked to domestic animals: measles, pertussis, smallpox, tuberculosis, taenid worms, and falciparal malaria. The majority are civilization pathogens, although I have included others whose evolutionary origins have traditionally been ascribed to domestic animals. The strongest evidence for a domestic-animal origin exists for measles and pertussis, although the data do not exclude a non-domestic origin. As for the other pathogens, the evidence currently available makes it difficult to determine if the domestic-origin hypothesis is supported or refuted; in fact, intriguing data for tuberculosis and taenid worms suggests that transmission may occur as easily from humans to domestic animals. These findings do not abrogate the importance of agriculture in disease transmission; rather, if anything, they suggest an alternative, more complex series of effects than previously elucidated. Rather than domestication, the broader force for human pathogen evolution could be ecological change, namely anthropogenic modification of the environment. This is supported by evidence that many current emerging infectious diseases are associated with human modification of the environment. Agriculture may have changed the transmission ecology of pre-existing human pathogens, increased the success of pre-existing pathogen vectors, resulted in novel interactions between humans and wildlife, and, through the domestication of animals, provided a stable conduit for human

  1. Human mobility networks and persistence of rapidly mutating pathogens.

    Science.gov (United States)

    Aleta, Alberto; Hisi, Andreia N S; Meloni, Sandro; Poletto, Chiara; Colizza, Vittoria; Moreno, Yamir

    2017-03-01

    Rapidly mutating pathogens may be able to persist in the population and reach an endemic equilibrium by escaping hosts' acquired immunity. For such diseases, multiple biological, environmental and population-level mechanisms determine the dynamics of the outbreak, including pathogen's epidemiological traits (e.g. transmissibility, infectious period and duration of immunity), seasonality, interaction with other circulating strains and hosts' mixing and spatial fragmentation. Here, we study a susceptible-infected-recovered-susceptible model on a metapopulation where individuals are distributed in sub-populations connected via a network of mobility flows. Through extensive numerical simulations, we explore the phase space of pathogen's persistence and map the dynamical regimes of the pathogen following emergence. Our results show that spatial fragmentation and mobility play a key role in the persistence of the disease whose maximum is reached at intermediate mobility values. We describe the occurrence of different phenomena including local extinction and emergence of epidemic waves, and assess the conditions for large-scale spreading. Findings are highlighted in reference to previous studies and to real scenarios. Our work uncovers the crucial role of hosts' mobility on the ecological dynamics of rapidly mutating pathogens, opening the path for further studies on disease ecology in the presence of a complex and heterogeneous environment.

  2. Cold plasma inactivation of human pathogens on foods and regulatory status update

    Science.gov (United States)

    Contamination of foods with human pathogens such as Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, norovirus, and other pathogens is an ongoing challenge for growers and processors. In recent years, cold plasma has emerged as a promising antimicrobial treatment for fresh and fresh-cut...

  3. Extremely strict ideals in Banach spaces

    Indian Academy of Sciences (India)

    Motivated by the notion of an ideal introduced by Godefroy {\\it et al.} ({\\it Studia Math.} {\\bf 104} (1993) 13–59), in this article, we introduce and study the notion of an extremely strict ideal. For a Poulsen simplex K , we show that the space of affine continuous functions on K is an extremely strict ideal in the space of continuous ...

  4. Hyperbolic spaces are of strictly negative type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Kokkendorff, Simon L.; Markvorsen, Steen

    2002-01-01

    We study finite metric spaces with elements picked from, and distances consistent with, ambient Riemannian manifolds. The concepts of negative type and strictly negative type are reviewed, and the conjecture that hyperbolic spaces are of strictly negative type is settled, in the affirmative...

  5. Extremely strict ideals in Banach spaces

    Indian Academy of Sciences (India)

    Abstract. Motivated by the notion of an ideal introduced by Godefroy et al. (Stu- dia Math. 104 (1993) 13–59), in this article, we introduce and study the notion of an extremely strict ideal. For a Poulsen simplex K, we show that the space of affine contin- uous functions on K is an extremely strict ideal in the space of continuous ...

  6. Human enteric pathogen internalization by root uptake into food crops

    Science.gov (United States)

    With an increasing number of outbreaks and illnesses associated with pre-harvest contaminated produce, understanding the potential and mechanisms of produce contamination by enteric pathogens can aid in the development of preventative measures and post-harvest processing to reduce microbial populati...

  7. Identification of some human pathogenic fungi using four DNA ...

    African Journals Online (AJOL)

    Stocks from pathogenic fungi isolated from infected areas on different patients, around Lagos-Nigeria were analysed using molecular methods (DNA extraction, PCR-RFLP and DNA sequencing). Four DNA extraction protocols were employed in the identification of the fungal isolates. Sixteen different fungal isolates were ...

  8. Phylogenetic reassessment of Nigrospora: Ubiquitous endophytes, plant and human pathogens

    NARCIS (Netherlands)

    Wang, M.; Liu, F.; Crous, P.W.; Cai, L.

    2017-01-01

    Species of Nigrospora commonly occur as plant pathogens, endophytes or saprobes, and have been shown to be extremely interesting for the discovery of novel metabolites. The familial placement, as well as phylogenetic relationships among Nigrospora species remain ambiguous. In this study, Nigrospora

  9. Genome sequence of the human pathogen Vibrio cholerae Amazonia.

    NARCIS (Netherlands)

    Thompson, C.C.; Marin, M.A.; Dias, G.M.; Dutilh, B.E.; Edwards, R.A.; Iida, T.; Thompson, F.L.; Vicente, A.C.

    2011-01-01

    Vibrio cholerae O1 Amazonia is a pathogen that was isolated from cholera-like diarrhea cases in at least two countries, Brazil and Ghana. Based on multilocus sequence analysis, this lineage belongs to a distinct profile compared to strains from El Tor and classical biotypes. The genomic analysis

  10. Characterization of pathogenic germline mutations in human Protein Kinases

    Directory of Open Access Journals (Sweden)

    Orengo Christine A

    2011-07-01

    Full Text Available Abstract Background Protein Kinases are a superfamily of proteins involved in crucial cellular processes such as cell cycle regulation and signal transduction. Accordingly, they play an important role in cancer biology. To contribute to the study of the relation between kinases and disease we compared pathogenic mutations to neutral mutations as an extension to our previous analysis of cancer somatic mutations. First, we analyzed native and mutant proteins in terms of amino acid composition. Secondly, mutations were characterized according to their potential structural effects and finally, we assessed the location of the different classes of polymorphisms with respect to kinase-relevant positions in terms of subfamily specificity, conservation, accessibility and functional sites. Results Pathogenic Protein Kinase mutations perturb essential aspects of protein function, including disruption of substrate binding and/or effector recognition at family-specific positions. Interestingly these mutations in Protein Kinases display a tendency to avoid structurally relevant positions, what represents a significant difference with respect to the average distribution of pathogenic mutations in other protein families. Conclusions Disease-associated mutations display sound differences with respect to neutral mutations: several amino acids are specific of each mutation type, different structural properties characterize each class and the distribution of pathogenic mutations within the consensus structure of the Protein Kinase domain is substantially different to that for non-pathogenic mutations. This preferential distribution confirms previous observations about the functional and structural distribution of the controversial cancer driver and passenger somatic mutations and their use as a proxy for the study of the involvement of somatic mutations in cancer development.

  11. Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

    Energy Technology Data Exchange (ETDEWEB)

    Colwell, Rita [University of Maryland

    2012-06-01

    Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

  12. Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages

    OpenAIRE

    Friesenhagen, Judith; Boergeling, Yvonne; Hrincius, Eike; Ludwig, Stephan; Roth, Johannes; Viemann, Dorothee

    2012-01-01

    Human blood-derived macrophages are non-permissive for influenza virus propagation, and fail to elicit inflammatory and antiviral responses upon infection with high pathogenic avian influenza viruses.

  13. Impacts of climate change on indirect human exposure to pathogens and chemicals from agriculture.

    Science.gov (United States)

    Boxall, Alistair; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter; Haygarth, Philip; Hutchinson, Thomas; Kovats, Sari; Leonardi, Giovanni; Levy, Leonard; Nichols, Gordon; Parsons, Simon; Potts, Laura; Stone, David; Topp, Edward; Turley, David; Walsh, Kerry; Wellington, Elizabeth; Williams, Richard

    2010-05-01

    Climate change is likely to affect the nature of pathogens/ chemicals in the environment and their fate and transport. We assess the implications of climate change for changes in human exposures to pathogens/chemicals in agricultural systems in the UK and discuss the effects on health impacts, using expert input and literature on climate change; health effects from exposure to pathogens/chemicals arising from agriculture; inputs of chemicals/pathogens to agricultural systems; and human exposure pathways for pathogens/chemicals in agricultural systems. We established the evidence base for health effects of chemicals/pathogens in the agricultural environment; determined the potential implications of climate change on chemical/pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of various contaminants. We merged data to assess the implications of climate change in terms of indirect human exposure to pathogens/chemicals in agricultural systems, and defined recommendations on future research and policy changes to manage adverse increases in risks.

  14. Migrating microbes: what pathogens can tell us about population movements and human evolution.

    Science.gov (United States)

    Houldcroft, Charlotte J; Ramond, Jean-Baptiste; Rifkin, Riaan F; Underdown, Simon J

    2017-08-01

    The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases. This study explores which pathogens leave traces in the archaeological record, and whether there are realistic prospects that these pathogens can be recovered from sub-Saharan African archaeological contexts. Three stories are then presented of germs on a journey. The first is the story of HIV's spread on the back of colonialism and the railway networks over the last 150 years. The second involves the spread of Schistosoma mansoni, a parasite which shares its history with the trans-Atlantic slave trade and the origins of fresh-water fishing. Finally, we discuss the tantalising hints of hominin migration and interaction found in the genome of human herpes simplex virus 2. Evidence from modern African pathogen genomes can provide data on human behaviour and migration in deep time and contribute to the improvement of human quality-of-life and longevity.

  15. Human soil-borne pathogens and risks associated with land use change

    Science.gov (United States)

    Pereg, Lily

    2017-04-01

    Soil is a source of pathogenic, neutral and beneficial microorganisms. Natural events and anthropogenic activity can affect soil biodiversity and influence the balance and distribution of soil-borne human pathogens. Important bacterial and fungal pathogens, such as Bacillus anthracis, Coxiella bernetii, Clostridium tetani, Escherichia coli 0157:H7, Listeria monocytogenes, Aspergillus fumigatus and Sporothrix schenckii will be discussed. This presentation will concentrate on soil pathogenic microorganisms and the effects of land use change on their prevalence and distribution. In particular, the potential of agricultural soil cultivation to enhance pathogen transmission to human through the release of soil microbes into the air attached to dust particles, contamination of waterways and infection of food plants and animal. Emerging solutions, such as biocontrol and probiotics, will be discussed.

  16. The Food Production Environment and the Development of Antimicrobial Resistance in Human Pathogens of Animal Origin

    Directory of Open Access Journals (Sweden)

    Manjusha Lekshmi

    2017-03-01

    Full Text Available Food-borne pathogens are a serious human health concern worldwide, and the emergence of antibiotic-resistant food pathogens has further confounded this problem. Once-highly-efficacious antibiotics are gradually becoming ineffective against many important pathogens, resulting in severe treatment crises. Among several reasons for the development and spread of antimicrobial resistance, their overuse in animal food production systems for purposes other than treatment of infections is prominent. Many pathogens of animals are zoonotic, and therefore any development of resistance in pathogens associated with food animals can spread to humans through the food chain. Human infections by antibiotic-resistant pathogens such as Campylobacter spp., Salmonella spp., Escherichia coli and Staphylococcus aureus are increasing. Considering the human health risk due to emerging antibiotic resistance in food animal–associated bacteria, many countries have banned the use of antibiotic growth promoters and the application in animals of antibiotics critically important in human medicine. Concerted global efforts are necessary to minimize the use of antimicrobials in food animals in order to control the development of antibiotic resistance in these systems and their spread to humans via food and water.

  17. Impacts of climate change on indirect human exposure to pathogens and chemicals from agriculture.

    Science.gov (United States)

    Boxall, Alistair B A; Hardy, Anthony; Beulke, Sabine; Boucard, Tatiana; Burgin, Laura; Falloon, Peter D; Haygarth, Philip M; Hutchinson, Thomas; Kovats, R Sari; Leonardi, Giovanni; Levy, Leonard S; Nichols, Gordon; Parsons, Simon A; Potts, Laura; Stone, David; Topp, Edward; Turley, David B; Walsh, Kerry; Wellington, Elizabeth M H; Williams, Richard J

    2009-04-01

    Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. In this review, we used expert input and considered literature on climate change; health effects resulting from exposure to pathogens and chemicals arising from agriculture; inputs of chemicals and pathogens to agricultural systems; and human exposure pathways for pathogens and chemicals in agricultural systems. We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes.

  18. Airborne pathogens from dairy manure aerial irrigation and the human health risk

    Science.gov (United States)

    Borchardt, Mark A.; Burch, Tucker R

    2016-01-01

    Dairy manure, like the fecal excrement from any domesticated or wild animal, can contain pathogens capable of infecting humans and causing illness or even death. Pathogens in dairy manure can be broadly divided into categories of taxonomy or infectiousness. Dividing by taxonomy there are three pathogen groups in dairy manure: viruses (e.g., bovine rotavirus), bacteria (e.g., Salmonella species), and protozoa (e.g., Cryptosporidium parvum). There are two categories of infectiousness for pathogens found in animals: those that are zoonotic and those that are not. A zoonotic pathogen is one that can infect both human and animal hosts. Some zoonotic pathogens found in dairy manure cause illness in both hosts (e.g., Salmonella) while other zoonotic pathogens, like Escherichia coli O157:H7, (enterohemorrhagic E. coli (EHEC)) cause illness only in humans. As a general rule, the gastrointestinal viruses found in dairy manure are not zoonotic. While there are exceptions (e.g., rare reports of bovine rotavirus infecting children), for the most part the viruses in dairy manure are not a human health concern. The primary concerns are the zoonotic bacteria and protozoa in dairy manure.

  19. Migrating microbes: what pathogens can tell us about population movements and human evolution

    OpenAIRE

    Houldcroft, Charlotte Jane; Ramond, J-B; Rifkin, RF; Underdown, SJ

    2017-01-01

    Background: The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen’s genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa,...

  20. Finite Metric Spaces of Strictly negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    If a finite metric space is of strictly negative type then its transfinite diameter is uniquely realized by an infinite extent (“load vector''). Finite metric spaces that have this property include all trees, and all finite subspaces of Euclidean and Hyperbolic spaces. We prove that if the distance...... matrix of a finite metric space is both hypermetric and regular, then it is of strictly negative type. We show that the strictly negative type finite subspaces of spheres are precisely those which do not contain two pairs of antipodal points....

  1. Occurrence of human pathogenic Clostridium botulinum among healthy dairy animals: an emerging public health hazard.

    Science.gov (United States)

    Abdel-Moein, Khaled A; Hamza, Dalia A

    2016-01-01

    The current study was conducted to investigate the occurrence of human pathogenic Clostridium botulinum in the feces of dairy animals. Fecal samples were collected from 203 apparently healthy dairy animals (50 cattle, 50 buffaloes, 52 sheep, 51 goats). Samples were cultured to recover C. botulinum while human pathogenic C. botulinum strains were identified after screening of all C. botulinum isolates for the presence of genes that encode toxins type A, B, E, F. The overall prevalence of C. botulinum was 18.7% whereas human pathogenic C. botulinum strains (only type A) were isolated from six animals at the rates of 2, 2, 5.8, and 2% for cattle, buffaloes, sheep, and goats, respectively. High fecal carriage rates of C. botulinum among apparently healthy dairy animals especially type A alarm both veterinary and public health communities for a potential role which may be played by dairy animals in the epidemiology of such pathogen.

  2. Identification of DNA Methyltransferase Genes in Human Pathogenic Bacteria by Comparative Genomics.

    Science.gov (United States)

    Brambila-Tapia, Aniel Jessica Leticia; Poot-Hernández, Augusto Cesar; Perez-Rueda, Ernesto; Rodríguez-Vázquez, Katya

    2016-06-01

    DNA methylation plays an important role in gene expression and virulence in some pathogenic bacteria. In this report, we describe DNA methyltransferases (MTases) present in human pathogenic bacteria and compared them with related species, which are not pathogenic or less pathogenic, based in comparative genomics. We performed a search in the KEGG database of the KEGG database orthology groups associated with adenine and cytosine DNA MTase activities (EC: 2.1.1.37, EC: 2.1.1.113 and EC: 2.1.1.72) in 37 human pathogenic species and 18 non/less pathogenic relatives and performed comparisons of the number of these MTases sequences according to their genome size, the DNA MTase type and with their non-less pathogenic relatives. We observed that Helicobacter pylori and Neisseria spp. presented the highest number of MTases while ten different species did not present a predicted DNA MTase. We also detected a significant increase of adenine MTases over cytosine MTases (2.19 vs. 1.06, respectively, p DNA MTases associated with type I restriction modification systems were more numerous than those associated with type III restriction modification systems (0.84 vs. 0.17, p DNA MTases, indicating that the number of DNA MTases is related to the particular evolution and lifestyle of specific species, regulating the expression of virulence genes in some pathogenic bacteria.

  3. Phagocytosis of human erythrocytes by Naegleria is not related to species pathogenicity. A phase-contrast cinemicrographic study.

    Science.gov (United States)

    Scaglia, M; Gatti, S; Brustia, R; Chichino, G; Rondanelli, E G

    1991-01-01

    This phase contrast cinemicrographic study evaluated the phagocytic activity of Naegleria spp. (Naegleria fowleri, Naegleria australiensis and Naegleria lovaniensis) towards human red cells. Thus erythrophagocytosis, a marker of pathogeneicity for Entamoeba histolytica, did not correlate with virulence in either the pathogenic or non-pathogenic Naegleria spp. tested. Our study also revealed no quantitative differences in phagocytosis by Naegleria spp. of human erythrocytes.

  4. Hyperbolic spaces are of strictly negative type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Kokkendorff, Simon L.; Markvorsen, Steen

    2002-01-01

    We study finite metric spaces with elements picked from, and distances consistent with, ambient Riemannian manifolds. The concepts of negative type and strictly negative type are reviewed, and the conjecture that hyperbolic spaces are of strictly negative type is settled, in the affirmative....... The technique of the proof is subsequently applied to show that every compact manifold of negative type must have trivial fundamental group, and to obtain a necessary criterion for product manifolds to be of negative type....

  5. Human GBP1 does not localize to pathogen vacuoles but restricts Toxoplasma gondii.

    Science.gov (United States)

    Johnston, Ashleigh C; Piro, Anthony; Clough, Barbara; Siew, Malvin; Virreira Winter, Sebastian; Coers, Jörn; Frickel, Eva-Maria

    2016-08-01

    Guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases that are transcriptionally upregulated upon infection with intracellular pathogens. Murine GBPs (mGBPs) including mGBP1 and 2 localize to and disrupt pathogen-containing vacuoles (PVs) resulting in the cell-autonomous clearing or innate immune detection of PV-resident pathogens. Human GBPs (hGBPs) are known to exert antiviral host defense and activate the NLRP3 inflammasome, but it is unclear whether hGBPs can directly recognize and control intravacuolar pathogens. Here, we report that endogenous or ectopically expressed hGBP1 fails to associate with PVs formed in human cells by the bacterial pathogens Chlamydia trachomatis or Salmonella typhimurium or the protozoan pathogen Toxoplasma gondii. While we find that hGBP1 expression has no discernible effect on intracellular replication of C. trachomatis and S. typhimurium, we observed enhanced early Toxoplasma replication in CRISPR hGBP1-deleted human epithelial cells. We thus identified a novel role for hGBP1 in cell-autonomous immunity that is independent of PV translocation, as observed for mGBPs. This study highlights fundamental differences between human and murine GBPs and underlines the need to study the functions of GBPs at cellular locations away from PVs. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

  6. Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

    Science.gov (United States)

    Qi, Wenbao; Jia, Weixin; Liu, Di; Li, Jing; Bi, Yuhai; Xie, Shumin; Li, Bo; Hu, Tao; Du, Yingying; Xing, Li; Zhang, Jiahao; Zhang, Fuchun; Wei, Xiaoman; Eden, John-Sebastian; Li, Huanan; Tian, Huaiyu; Li, Wei; Su, Guanming; Lao, Guangjie; Xu, Chenggang; Xu, Bing; Liu, Wenjun; Zhang, Guihong; Ren, Tao; Holmes, Edward C; Cui, Jie; Shi, Weifeng; Gao, George F; Liao, Ming

    2018-01-15

    Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed

  7. The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens.

    Science.gov (United States)

    van der Veen, Stijn; Tang, Christoph M

    2015-02-01

    During colonization and disease, bacterial pathogens must survive the onslaught of the host immune system. A key component of the innate immune response is the generation of reactive oxygen and nitrogen species by phagocytic cells, which target and disrupt pathogen molecules, particularly DNA, and the base excision repair (BER) pathway is the most important mechanism for the repair of such oxidative DNA damage. In this Review, we discuss how the human-specific pathogens Mycobacterium tuberculosis, Helicobacter pylori and Neisseria meningitidis have evolved specialized mechanisms of DNA repair, particularly their BER pathways, compared with model organisms such as Escherichia coli. This specialization in DNA repair is likely to reflect the distinct niches occupied by these important human pathogens in the host.

  8. Bottlenecks in the transmission of antibiotic resistance from natural ecosystems to human bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Jose L Martinez

    2012-01-01

    Full Text Available It is generally accepted that resistance genes acquired by human pathogens trough horizontal gene transfer have been originated in environmental, non pathogenic bacteria. As the consequence, there exists an increasing concern on the role that natural, non-clinical ecosystems, may play on the evolution of resistance. Recent studies have shown that the variability of determinants that can provide antibiotic resistance upon their expression in a heterologous host is much larger than what is actually found in human pathogens. Along the review, the role that different processes as founder effect, ecological connectivity, fitness costs or second-order selection may have on the establishment of a specific resistance determinant in the population of bacterial pathogens is analysed.

  9. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia

    OpenAIRE

    Muñoz, José F.; Gauthier, Gregory M.; Desjardins, Christopher A.; Gallo, Juan E.; Holder, Jason; Sullivan, Thomas D.; Marty, Amber J.; Carmen, John C.; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret

    2015-01-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated...

  10. Prevalence of plant beneficial and human pathogenic bacteria isolated from salad vegetables in India.

    Science.gov (United States)

    Nithya, Angamuthu; Babu, Subramanian

    2017-03-14

    The study aimed at enumerating, identifying and categorizing the endophytic cultivable bacterial community in selected salad vegetables (carrot, cucumber, tomato and onion). Vegetable samples were collected from markets of two vegetable hot spot growing areas, during two different crop harvest seasons. Crude and diluted vegetable extracts were plated and the population of endophytic bacteria was assessed based on morphologically distinguishable colonies. The bacterial isolates were identified by growth in selective media, biochemical tests and 16S rRNA gene sequencing. The endophytic population was found to be comparably higher in cucumber and tomato in both of the sampling locations, whereas lower in carrot and onion. Bacterial isolates belonged to 5 classes covering 46 distinct species belonging to 19 genera. Human opportunistic pathogens were predominant in carrot and onion, whereas plant beneficial bacteria dominated in cucumber and tomato. Out of the 104 isolates, 16.25% are human pathogens and 26.5% are human opportunistic pathogens. Existence of a high population of plant beneficial bacteria was found to have suppressed the population of plant and human pathogens. There is a greater potential to study the native endophytic plant beneficial bacteria for developing them as biocontrol agents against human pathogens that are harboured by plants.

  11. Antimicrobial activity of Uncaria tomentosa against oral human pathogens

    OpenAIRE

    Ccahuana-Vasquez, Renzo Alberto; Ferreira dos Santos, Silvana Soléo; Koga-Ito, Cristiane Yumi [UNESP; Cardoso Jorge, Antonio Olavo

    2007-01-01

    Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria t...

  12. Targeted Disruption of Melanin Biosynthesis Genes in the Human Pathogenic Fungus Lomentospora prolificans and Its Consequences for Pathogen Survival

    Directory of Open Access Journals (Sweden)

    Ayat Al-Laaeiby

    2016-03-01

    Full Text Available The dematiaceous (melanised fungus Lomentospora (Scedosporium prolificans is a life-threatening opportunistic pathogen of immunocompromised humans, resistant to anti-fungal drugs. Melanin has been shown to protect human pathogenic fungi against antifungal drugs, oxidative killing and environmental stresses. To determine the protective role of melanin in L. prolificans to oxidative killing (H2O2, UV radiation and the polyene anti-fungal drug amphotericin B, targeted gene disruption was used to generate mutants of the pathogen lacking the dihydroxynaphthalene (DHN-melanin biosynthetic enzymes polyketide synthase (PKS1, tetrahydroxynapthalene reductase (4HNR and scytalone dehydratase (SCD1. Infectious propagules (spores of the wild-type strain 3.1 were black/brown, whereas spores of the PKS-deficient mutant ΔLppks1::hph were white. Complementation of the albino mutant ΔLppks1::hph restored the black-brown spore pigmentation, while the 4HNR-deficient mutant ΔLp4hnr::hph and SCD-deficient mutant ΔLpscd1::hph both produced orange-yellow spores. The mutants ΔLppks1::hph and ΔLp4hnr::hph showed significant reductions in spore survival following H2O2 treatment, while spores of ΔLpscd1::hph and the ΔLppks1::hph complemented strain ΔLppks1::hph:PKS showed spore survivals similar to strain 3.1. Spores of the mutants ΔLp4hnr::hph and ΔLpscd1::hph and complemented strain ΔLppks1::hph:PKS showed spore survivals similar to 3.1 following exposure to UV radiation, but survival of ΔLppks1::hph spores was significantly reduced compared to the wild-type strain. Strain 3.1 and mutants ΔLp4hnr::hph and ΔLppks1::hph:PKS were resistant to amphotericin B while, paradoxically, the PKS1- and SCD1-deficient mutants showed significant increases in growth in the presence of the antifungal drug. Taken together, these results show that while melanin plays a protective role in the survival of the pathogen to oxidative killing and UV radiation, melanin does not

  13. Targeted Disruption of Melanin Biosynthesis Genes in the Human Pathogenic Fungus Lomentospora prolificans and Its Consequences for Pathogen Survival.

    Science.gov (United States)

    Al-Laaeiby, Ayat; Kershaw, Michael J; Penn, Tina J; Thornton, Christopher R

    2016-03-24

    The dematiaceous (melanised) fungus Lomentospora (Scedosporium) prolificans is a life-threatening opportunistic pathogen of immunocompromised humans, resistant to anti-fungal drugs. Melanin has been shown to protect human pathogenic fungi against antifungal drugs, oxidative killing and environmental stresses. To determine the protective role of melanin in L. prolificans to oxidative killing (H₂O₂), UV radiation and the polyene anti-fungal drug amphotericin B, targeted gene disruption was used to generate mutants of the pathogen lacking the dihydroxynaphthalene (DHN)-melanin biosynthetic enzymes polyketide synthase (PKS1), tetrahydroxynapthalene reductase (4HNR) and scytalone dehydratase (SCD1). Infectious propagules (spores) of the wild-type strain 3.1 were black/brown, whereas spores of the PKS-deficient mutant ΔLppks1::hph were white. Complementation of the albino mutant ΔLppks1::hph restored the black-brown spore pigmentation, while the 4HNR-deficient mutant ΔLp4hnr::hph and SCD-deficient mutant ΔLpscd1::hph both produced orange-yellow spores. The mutants ΔLppks1::hph and ΔLp4hnr::hph showed significant reductions in spore survival following H₂O₂ treatment, while spores of ΔLpscd1::hph and the ΔLppks1::hph complemented strain ΔLppks1::hph:PKS showed spore survivals similar to strain 3.1. Spores of the mutants ΔLp4hnr::hph and ΔLpscd1::hph and complemented strain ΔLppks1::hph:PKS showed spore survivals similar to 3.1 following exposure to UV radiation, but survival of ΔLppks1::hph spores was significantly reduced compared to the wild-type strain. Strain 3.1 and mutants ΔLp4hnr::hph and ΔLppks1::hph:PKS were resistant to amphotericin B while, paradoxically, the PKS1- and SCD1-deficient mutants showed significant increases in growth in the presence of the antifungal drug. Taken together, these results show that while melanin plays a protective role in the survival of the pathogen to oxidative killing and UV radiation, melanin does not

  14. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Science.gov (United States)

    Sutherland, Kathryn Patterson; Shaban, Sameera; Joyner, Jessica L; Porter, James W; Lipp, Erin K

    2011-01-01

    Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  15. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

    Directory of Open Access Journals (Sweden)

    Kathryn Patterson Sutherland

    Full Text Available Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS, a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens to a marine invertebrate (A. palmata. These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  16. Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

    Directory of Open Access Journals (Sweden)

    Parisa Shokryazdan

    2014-01-01

    Full Text Available The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits.

  17. Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

    Science.gov (United States)

    Shokryazdan, Parisa; Sieo, Chin Chin; Kalavathy, Ramasamy; Liang, Juan Boo; Alitheen, Noorjahan Banu; Faseleh Jahromi, Mohammad; Ho, Yin Wan

    2014-01-01

    The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits. PMID:25105147

  18. Potential human pathogenic bacteria in a mixed urban watershed as revealed by pyrosequencing.

    Directory of Open Access Journals (Sweden)

    A Mark Ibekwe

    Full Text Available Current microbial source tracking (MST methods for water depend on testing for fecal indicator bacterial counts or specific marker gene sequences to identify fecal contamination where potential human pathogenic bacteria could be present. In this study, we applied 454 high-throughput pyrosequencing to identify bacterial pathogen DNA sequences, including those not traditionally monitored by MST and correlated their abundances to specific sources of contamination such as urban runoff and agricultural runoff from concentrated animal feeding operations (CAFOs, recreation park area, waste-water treatment plants, and natural sites with little or no human activities. Samples for pyrosequencing were surface water, and sediment collected from 19 sites. A total of 12,959 16S rRNA gene sequences with average length of ≤400 bp were obtained, and were assigned to corresponding taxonomic ranks using ribosomal database project (RDP, Classifier and Greengenes databases. The percent of total potential pathogens were highest in urban runoff water (7.94%, agricultural runoff sediment (6.52%, and Prado Park sediment (6.00%, respectively. Although the numbers of DNA sequence tags from pyrosequencing were very high for the natural site, corresponding percent potential pathogens were very low (3.78-4.08%. Most of the potential pathogenic bacterial sequences identified were from three major phyla, namely, Proteobacteria, Bacteroidetes, and Firmicutes. The use of deep sequencing may provide improved and faster methods for the identification of pathogen sources in most watersheds so that better risk assessment methods may be developed to enhance public health.

  19. Effect of pathogenic yeasts on human platelet aggregation

    Directory of Open Access Journals (Sweden)

    Neiva Teresinha de Jesus Carvalho

    2003-01-01

    Full Text Available We investigated the effects of Candida albicans, Cryptococcus neoformans and the respective culture supernatants on human platelet aggregation (PA. Both yeasts were unable to aggregate the platelets directly. On the other hand, cells of these yeasts significantly (P < 0.01 inhibited PA at concentrations equal to or higher than 1 x 10(6 cells/mL for C. albicans and equal to or higher than 1 x 10(5 cells/mL for C. neoformans. When the supernatants of one-week broth cultures were added to the activated platelets no inhibition in aggregation was observed. Apparently somatic components of these yeasts, but not their metabolic products, exert an antagonistic effect on the aggregation of human platelets, possibly aiding the fungi in their evasion of the microbicidal defense system during vascular dissemination.

  20. Strictly convex functions on complete Finsler manifolds

    Indian Academy of Sciences (India)

    ... Refresher Courses · Symposia · Live Streaming. Home; Journals; Proceedings – Mathematical Sciences; Volume 126; Issue 4. Strictly convex functions on complete Finsler manifolds. YOE ITOKAWA KATSUHIRO SHIOHAMA BANKTESHWAR TIWARI. Research Article Volume 126 Issue 4 October 2016 pp 623-627 ...

  1. Finite Metric Spaces of Strictly Negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul; Lisonek, P.; Markvorsen, Steen

    1998-01-01

    We prove that, if a finite metric space is of strictly negative type, then its transfinite diameter is uniquely realized by the infinite extender (load vector). Finite metric spaces that have this property include all spaces on two, three, or four points, all trees, and all finite subspaces of Eu...

  2. Aerially transmitted human fungal pathogens: what can we learn from metagenomics and comparative genomics?

    Science.gov (United States)

    Aliouat-Denis, Cécile-Marie; Chabé, Magali; Delhaes, Laurence; Dei-Cas, Eduardo

    2014-01-01

    In the last few decades, aerially transmitted human fungal pathogens have been increasingly recognized to impact the clinical course of chronic pulmonary diseases, such as asthma, cystic fibrosis or chronic obstructive pulmonary disease. Thanks to recent development of culture-free high-throughput sequencing methods, the metagenomic approaches are now appropriate to detect, identify and even quantify prokaryotic or eukaryotic microorganism communities inhabiting human respiratory tract and to access the complexity of even low-burden microbe communities that are likely to play a role in chronic pulmonary diseases. In this review, we explore how metagenomics and comparative genomics studies can alleviate fungal culture bottlenecks, improve our knowledge about fungal biology, lift the veil on cross-talks between host lung and fungal microbiota, and gain insights into the pathogenic impact of these aerially transmitted fungi that affect human beings. We reviewed metagenomic studies and comparative genomic analyses of carefully chosen microorganisms, and confirmed the usefulness of such approaches to better delineate biology and pathogenesis of aerially transmitted human fungal pathogens. Efforts to generate and efficiently analyze the enormous amount of data produced by such novel approaches have to be pursued, and will potentially provide the patients suffering from chronic pulmonary diseases with a better management. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  3. Antimicrobial activity of Uncaria tomentosa against oral human pathogens.

    Science.gov (United States)

    Ccahuana-Vasquez, Renzo Alberto; Santos, Silvana Soléo Ferreira dos; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2007-01-01

    Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria tomentosa was tested in vitro to determine the minimum inhibitory concentration (MIC) on selected microbial strains. The tested strains were oral clinical isolates of Streptococcus mutans, Staphylococcus spp., Candida albicans, Enterobacteriaceae and Pseudomonas aeruginosa. The tested concentrations of Uncaria tomentosa ranged from 0.25-5% in Müeller-Hinton agar. Three percent Uncaria tomentosa inhibited 8% of Enterobacteriaceae isolates, 52% of S. mutans and 96% of Staphylococcus spp. The tested concentrations did not present inhibitory effect on P. aeruginosa and C. albicans. It could be concluded that micropulverized Uncaria tomentosa presented antimicrobial activity on Enterobacteriaceae, S. mutans and Staphylococcus spp. isolates.

  4. Antibacterial activity of some medicinal plants against selected human pathogenic bacteria.

    Science.gov (United States)

    Khan, Usman Ali; Rahman, Hazir; Niaz, Zeeshan; Qasim, Muhammad; Khan, Jafar; Tayyaba; Rehman, Bushra

    2013-12-01

    Medicinal plants are traditionally used for the treatment of human infections. The present study was undertaken to investigate Bergenia ciliata, Jasminum officinale, and Santalum album for their potential activity against human bacterial pathogens. B. ciliata, J. officinale, and S. album extracts were prepared in cold and hot water. The activity of plant extracts and selected antibiotics was evaluated against five bacterial pathogens including Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Pseudomonas aeruginosa, and Escherichia coli using agar well diffusion method. Among the three medicinal plants, B. ciliata extracts displayed potential activity against bacterial pathogens. Cold water extract of Bergenia ciliate showed the highest activity against B. subtilis, which is comparable with a zone of inhibition exhibited by ceftriaxone and erythromycin. J. officinale and S. album extracts demonstrated variable antibacterial activity. Further studies are needed to explore the novel antibacterial bioactive molecules.

  5. Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms.

    Science.gov (United States)

    Beatty, Jennifer K; Akierman, Sarah V; Motta, Jean-Paul; Muise, Stacy; Workentine, Matthew L; Harrison, Joe J; Bhargava, Amol; Beck, Paul L; Rioux, Kevin P; McKnight, Gordon Webb; Wallace, John L; Buret, Andre G

    2017-05-01

    Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic - even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights

  6. Avian reservoirs and zoonotic potential of the emerging human pathogen Helicobacter canadensis

    DEFF Research Database (Denmark)

    Waldenström, J.; On, Stephen L.W.; Ottvall, R.

    2003-01-01

    testing; four strains were characterized by 16S rRNA gene sequence analysis. The results clearly identified the bird isolates as Helicobacter canadensis, recently described as an emerging human pathogen. This is the first report of an animal reservoir for this organism and of its presence in Europe...

  7. Gene Expression Platform for Synthetic Biology in the Human Pathogen Streptococcus pneumoniae

    NARCIS (Netherlands)

    Sorg, Robin A; Kuipers, Oscar P; Veening, Jan-Willem

    2015-01-01

    The human pathogen Streptococcus pneumoniae (pneumococcus) is a bacterium that owes its success to complex gene expression regulation patterns on both the cellular and the population level. Expression of virulence factors enables a mostly hazard-free presence of the commensal, in balance with the

  8. Disinfection and removal of human pathogenic bacteria in arctic waste stabilization ponds

    DEFF Research Database (Denmark)

    Huang, Yannan; Hansen, Lisbeth Truelstrup; Ragush, Colin M.

    2017-01-01

    cool summer treatment season. With relevance to public health, the objectives of this paper were to determine if treatment in arctic WSPs resulted in the disinfection (i.e., removal of fecal indicator bacteria, Escherichia coli) and removal of selected human bacterial pathogens from the treated...

  9. CEACAM3-mediated phagocytosis of human-specific bacterial pathogens involves the adaptor molecule Nck

    OpenAIRE

    Peterson, Lisa

    2010-01-01

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are exploited by human-specific pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella and Haemophilus species. As opsonin-independent phagocytosis of CEACAM-binding Neisseria depends on Src-family protein tyrosine kinase (PTK) phosphorylation of the CEACAM3 ...

  10. wKinMut-2: Identification and Interpretation of Pathogenic Variants in Human Protein Kinases

    DEFF Research Database (Denmark)

    Vazquez, Miguel; Pons, Tirso; Brunak, Søren

    2016-01-01

    forest approach. To understand the biological mechanisms causative of human diseases and cancer, information from pertinent reference knowledgebases and the literature is automatically mined, digested and homogenized. Variants are visualized in their structural contexts and residues affecting catalytic...... is often scattered across different sources, which makes the integrative analysis complex and laborious. wKinMut-2 constitutes a solution to facilitate the interpretation of the consequences of human protein kinase variation. Nine methods predict their pathogenicity, including a kinase-specific random...

  11. Antimicrobial effect of polyphenols from apple skins on human bacterial pathogens

    OpenAIRE

    Alberto,María Rosa; Rinsdahl Canavosio,Matías Andrés; Manca de Nadra,María Cristina

    2006-01-01

    Apples possess many beneficial properties for the human health related with their high content in phenolic compounds. The antimicrobial effect of these compounds from the skin of two apple varieties, Royal Gala and Granny Smith, against human pathogens was examined. The phenolic compounds were extracted with the following solvents: A, acetone: water: acetic acid; B, ethyl acetate: methanol: water and C, ethanol: water. Total phenolic, flavonoid and non-flavonoid contents were analyzed in the ...

  12. Exserohilum rostratum: characterization of a cross-kingdom pathogen of plants and humans.

    Directory of Open Access Journals (Sweden)

    Kalpana Sharma

    Full Text Available Pathogen host shifts represent a major source of new infectious diseases. There are several examples of cross-genus host jumps that have caused catastrophic epidemics in animal and plant species worldwide. Cross-kingdom jumps are rare, and are often associated with nosocomial infections. Here we provide an example of human-mediated cross-kingdom jumping of Exserohilum rostratum isolated from a patient who had received a corticosteroid injection and died of fungal meningitis in a Florida hospital in 2012. The clinical isolate of E. rostratum was compared with two plant pathogenic isolates of E. rostratum and an isolate of the closely related genus Bipolaris in terms of morphology, phylogeny, and pathogenicity on one C3 grass, Gulf annual rye grass (Lolium multiflorum, and two C4 grasses, Japanese stilt grass (Microstegium vimineum and bahia grass (Paspalum notatum. Colony growth and color, as well as conidia shape and size were the same for the clinical and plant isolates of E. rostratum, while these characteristics differed slightly for the Bipolaris sp. isolate. The plant pathogenic and clinical isolates of E. rostratum were indistinguishable based on morphology and ITS and 28S rDNA sequence analysis. The clinical isolate was as pathogenic to all grass species tested as the plant pathogenic strains that were originally isolated from plant hosts. The clinical isolate induced more severe symptoms on stilt grass than on rye grass, while this was the reverse for the plant isolates of E. rostratum. The phylogenetic similarity between the clinical and plant-associated E. rostratum isolates and the ability of the clinical isolate to infect plants suggests that a plant pathogenic strain of E. rostratum contaminated the corticosteroid injection fluid and was able to cause systemic disease in the affected patient. This is the first proof that a clinical isolate of E. rostratum is also an effective plant pathogen.

  13. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand.

    Directory of Open Access Journals (Sweden)

    Sarah L James

    2016-06-01

    Full Text Available Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development.This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation, in homologous and heterologous serum-isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera.Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam-like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross-reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes.

  14. Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types.

    Science.gov (United States)

    Menzo, Stefano; Ciavattini, Andrea; Bagnarelli, Patrizia; Marinelli, Katia; Sisti, Stefano; Clementi, Massimo

    2008-07-04

    Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings. In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000-2007, were analyzed using PCR amplification of a 173-206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer. Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.

  15. Extremely strict ideals in Banach spaces

    Indian Academy of Sciences (India)

    the space of regular Borel measures, it is easy to see that with respect to the projection μ → μ|(0, 1), M is an extremely strict ideal in C([0, 1]) but as the Lebesgue measure is non-atomic, M. ∗. 1 is not the norm closed ..... (Grenoble) 28 (1978) 35–65. [10] Rao T S S R K, On ideals in Banach spaces, Rocky Mountain J. Math.

  16. Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans.

    Science.gov (United States)

    Zadoks, Ruth N; Middleton, John R; McDougall, Scott; Katholm, Jorgen; Schukken, Ynte H

    2011-12-01

    Mastitis, inflammation of the mammary gland, can be caused by a wide range of organisms, including gram-negative and gram-positive bacteria, mycoplasmas and algae. Many microbial species that are common causes of bovine mastitis, such as Escherichia coli, Klebsiella pneumoniae, Streptococcus agalactiae and Staphylococcus aureus also occur as commensals or pathogens of humans whereas other causative species, such as Streptococcus uberis, Streptococcus dysgalactiae subsp. dysgalactiae or Staphylococcus chromogenes, are almost exclusively found in animals. A wide range of molecular typing methods have been used in the past two decades to investigate the epidemiology of bovine mastitis at the subspecies level. These include comparative typing methods that are based on electrophoretic banding patterns, library typing methods that are based on the sequence of selected genes, virulence gene arrays and whole genome sequencing projects. The strain distribution of mastitis pathogens has been investigated within individual animals and across animals, herds, countries and host species, with consideration of the mammary gland, other animal or human body sites, and environmental sources. Molecular epidemiological studies have contributed considerably to our understanding of sources, transmission routes, and prognosis for many bovine mastitis pathogens and to our understanding of mechanisms of host-adaptation and disease causation. In this review, we summarize knowledge gleaned from two decades of molecular epidemiological studies of mastitis pathogens in dairy cattle and discuss aspects of comparative relevance to human medicine.

  17. Human milk blocks DC-SIGN - pathogen interaction via MUC1

    Directory of Open Access Journals (Sweden)

    Nathalie eKoning

    2015-03-01

    Full Text Available Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens, as well as long term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on DC and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is DC-SIGN, which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastro-intestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.

  18. Every member of the kingdom Animalia is a potential vector of human pathogens.

    Science.gov (United States)

    Patel, Seema

    2017-08-01

    Zoonotic diseases are a subset of infectious diseases, which account for enormous morbidity and mortality. Pathologies like malaria, rabies, Lyme disease, leptospirosis, avian flu etc. are microbe- and parasite-caused ailments, where the etiological agents are introduced into or on the human body via ticks, mosquitoes, birds, rodents, bats, and deer, among other members of kingdom Animalia. While some of the zoonotic diseases are well-investigated and caution taken against, a lot many are yet to be recognized. This ignorance costs health, and lives, especially in developing countries. To promote awareness regarding the risks of immunogenicity and pathogen dissemination by hitherto unknown non-plant organisms, the members of kingdom Animalia, this letter has been compiled. The vector exploitation mechanisms of the pathogens, and in silico evidences of conserved protein domains across the potential pathogen reservoirs have been mentioned to underline the importance of this topic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes.

    Science.gov (United States)

    Beres, Stephen B; Kachroo, Priyanka; Nasser, Waleed; Olsen, Randall J; Zhu, Luchang; Flores, Anthony R; de la Riva, Ivan; Paez-Mayorga, Jesus; Jimenez, Francisco E; Cantu, Concepcion; Vuopio, Jaana; Jalava, Jari; Kristinsson, Karl G; Gottfredsson, Magnus; Corander, Jukka; Fittipaldi, Nahuel; Di Luca, Maria Chiara; Petrelli, Dezemona; Vitali, Luca A; Raiford, Annessa; Jenkins, Leslie; Musser, James M

    2016-05-31

    For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that

  20. Potential human pathogenic bacteria in five hot springs in Eritrea revealed by next generation sequencing

    Science.gov (United States)

    Boga, Hamadi Iddi; Anami, Sylvester Elikana; Mehari, Tadesse; Budambula, Nancy L. M.

    2018-01-01

    Human pathogens can survive and grow in hot springs. For water quality assessment, Escherichia coli or Enterococci are the main thermotolerant enteric bacteria commonly used to estimate the load of pathogenic bacteria in water. However, most of the environmental bacteria are unculturable thus culture methods may cause bias in detection of most pathogens. Illumina sequencing can provide a more comprehensive and accurate insight into environmental bacterial pathogens, which can be used to develop better risk assessment methods and promote public health awareness. In this study, high-throughput Illumina sequencing was used to identify bacterial pathogens from five hot springs; Maiwooi, Akwar, Garbanabra, Elegedi and Gelti, in Eritrea. Water samples were collected from the five hot springs. Total community DNA was extracted from samples using the phenol-chloroform method. The 16S rRNA gene variable region (V4—V7) of the extracted DNA was amplified and library construction done according to Illumina sequencing protocol. The sequence reads (length >200 bp) from Illumina sequencing libraries ranged from 22,091 sequences in the wet sediment sample from Garbanabra to 155,789 sequences in the mat sample from Elegedi. Taxonomy was assigned to each OTU using BLASTn against a curated database derived from GreenGenes, RDPII, SILVA SSU Reference 119 and NCBI. The proportion of potential pathogens from the water samples was highest in Maiwooi (17.8%), followed by Gelti (16.7%), Akwar (13.6%) and Garbanabra (10.9%). Although the numbers of DNA sequence reads from Illumina sequencing were very high for the Elegedi (104,328), corresponding proportion of potential pathogens very low (3.6%). Most of the potential pathogenic bacterial sequences identified were from Proteobacteria and Firmicutes. Legionella and Clostridium were the most common detected genera with different species. Most of the potential pathogens were detected from the water samples. However, sequences belonging to

  1. Susceptibility of intact germinating Arabidopsis thaliana to human fungal pathogens Cryptococcus neoformans and C. gattii.

    Science.gov (United States)

    Warpeha, Katherine M; Park, Yoon-Dong; Williamson, Peter R

    2013-05-01

    The fungus Cryptococcus contributes a large global burden of infectious death in both HIV-infected and healthy individuals. As Cryptococcus is an opportunistic pathogen, much of the evolutionary pressure shaping virulence occurs in environments in contact with plants and soil. The present studies investigated inoculation of intact seeds of the common weed Arabidopsis thaliana with fungal cells over a 21-day period. C. gattii was the more virulent plant pathogen, resulting in disrupted germination as well as increased stem lodging, fungal burden, and plant tissue colocalization. C. neoformans was a less virulent plant pathogen but exhibited prolonged tissue residence within the cuticle and vascular spaces. Arabidopsis mutants of the PRN1 gene, which is involved in abiotic and biotic signaling affecting phenylalanine-derived flavonoids, showed altered susceptibility to cryptoccocal infections, suggesting roles for this pathway in cryptococcal defense. The fungal virulence factor laccase was also implicated in plant pathogenesis, as a cryptococcal lac1Δ strain was less virulent than wild-type fungi and was unable to colonize seedlings. In conclusion, these studies expand knowledge concerning the ecological niche of Cryptococcus by demonstrating the pathogenic capacity of the anamorphic form of cryptococcal cells against healthy seedlings under physiologically relevant conditions. In addition, an important role of laccase in plant as well as human virulence may suggest mechanisms for laccase retention and optimization during evolution of this fungal pathogen.

  2. Identification of tick-borne pathogens in ticks feeding on humans in Turkey.

    Directory of Open Access Journals (Sweden)

    Ömer Orkun

    2014-08-01

    Full Text Available The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara.A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph and Ha. parva.This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey

  3. Identification of tick-borne pathogens in ticks feeding on humans in Turkey.

    Science.gov (United States)

    Orkun, Ömer; Karaer, Zafer; Çakmak, Ayşe; Nalbantoğlu, Serpil

    2014-08-01

    The importance of tick-borne diseases is increasing all over the world, including Turkey. The tick-borne disease outbreaks reported in recent years and the abundance of tick species and the existence of suitable habitats increase the importance of studies related to the epidemiology of ticks and tick-borne pathogens in Turkey. The aim of this study was to investigate the presence of and to determine the infection rates of some tick-borne pathogens, including Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in the ticks removed from humans in different parts of Ankara. A total of 169 ticks belonging to the genus Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus were collected by removing from humans in different parts of Ankara. Ticks were molecularly screened for Babesia spp., Borrelia burgdorferi sensu lato and spotted fever group rickettsiae by PCR and sequencing analysis. We detected 4 Babesia spp.; B. crassa, B. major, B. occultans and B. rossi, one Borrelia spp.; B. burgdorferi sensu stricto and 3 spotted fever group rickettsiae; R. aeschlimannii, R. slovaca and R. hoogstraalii in the tick specimens analyzed. This is the report showing the presence of B. rossi in a region that is out of Africa and in the host species Ha. parva. In addition, B. crassa, for which limited information is available on its distribution and vector species, and B. occultans, for which no conclusive information is available on its presence in Turkey, were identified in Ha. parva and H. marginatum, respectively. Two human pathogenic rickettsia species (R. aeschlimannii and R. slovaca) were detected with a high prevalence in ticks. Additionally, B. burgdorferi sensu stricto was detected in unusual tick species (H. marginatum, H. excavatum, Hyalomma spp. (nymph) and Ha. parva). This study investigates both the distribution of several tick-borne pathogens affecting humans and animals, and the presence of new tick-borne pathogens in Turkey. More

  4. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Directory of Open Access Journals (Sweden)

    Matteo Fumagalli

    2011-11-01

    Full Text Available Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the

  5. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Science.gov (United States)

    Fumagalli, Matteo; Sironi, Manuela; Pozzoli, Uberto; Ferrer-Admetlla, Anna; Ferrer-Admettla, Anna; Pattini, Linda; Nielsen, Rasmus

    2011-11-01

    Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some

  6. Two-spotted cricket as an animal infection model of human pathogenic fungi.

    Science.gov (United States)

    Kochi, Yuto; Matsumoto, Yasuhiko; Sekimizu, Kazuhisa; Kaito, Chikara

    2017-11-22

    Invertebrate infection models that can be evaluated at human body temperature are limited. In this study, we utilized the two-spotted cricket, a heat-tolerant insect, as an animal infection model of human pathogenic fungi. Injection of human pathogenic fungi, including Candida albicans, Candida glabrata, and Cryptococcus neoformans killed crickets within 48 h at both 27˚C and 37˚C. The median lethal dose values (LD50 values) of C. albicans and C. glabrata against crickets were decreased at 37˚C compared to that at 27˚C, whereas the LD50 value of C. neoformans was not different between 27˚C and 37˚C. Heat-killed cells of the three different fungi also killed crickets, but the LD50 value of the heat-killed cells was higher than 5-fold that of live fungal cells in the respective species. C. neoformans gene-knockout strains of cna1, gpa1, and pka1, which are required for virulence in mammals, had greater LD50 values than the parent strain in crickets. These findings suggest that the two-spotted cricket is a valuable infection model of human pathogenic fungi that can be used to evaluate fungal virulence at variable temperatures, including 37˚C, and that the killing abilities of C. albicans and C. glabrata against animals are increased at 37˚C.

  7. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  8. Strictness Analysis and Denotational Abstract Interpretation

    DEFF Research Database (Denmark)

    Nielson, Flemming

    1988-01-01

    there and this sufices to make the framework applicable to strictness analysis for the lambda-calculus. This shows the possibility of a general theory for the analysis of functional programs and it gives more insight into the relative precision of the various analyses. In particular it is shown that a collecting (static......A theory of abstract interpretation () is developed for a typed lambda-calculus. The typed lambda-calculus may be viewed as the ''static'' part of a two-level denotational metalanguage for which abstract interpretation was developed by ). The present development relaxes a condition imposed...

  9. Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

    Directory of Open Access Journals (Sweden)

    Matthew T G Holden

    2009-03-01

    Full Text Available The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus. These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

  10. Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.

    Science.gov (United States)

    Holden, Matthew T G; Heather, Zoe; Paillot, Romain; Steward, Karen F; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C; Holroyd, Nancy E; Mungall, Karen; Quail, Michael A; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M; Spratt, Brian G; Jolley, Keith A; Maiden, Martin C J; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D; Robinson, Carl; Maskell, Duncan J; Parkhill, Julian; Waller, Andrew S

    2009-03-01

    The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.

  11. 7 CFR 28.441 - Strict Middling Yellow Stained Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Yellow Stained Color. 28.441 Section... Strict Middling Yellow Stained Color. Strict Middling Yellow Stained Color is color which is deeper than that of Strict Middling Tinged Color. [57 FR 34498, Aug. 5, 1992] ...

  12. 7 CFR 28.412 - Strict Middling Light Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Light Spotted Color. 28.412 Section 28... Light Spotted Color. Strict Middling Light Spotted Color is color which in spot or color, or both, is between Strict Middling Color and Strict Middling Spotted Color. ...

  13. Classification of human pathogen bacteria for early screening using electronic nose

    Science.gov (United States)

    Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

    2017-10-01

    This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

  14. Experimental annotation of the human pathogen Histoplasma capsulatum transcribed regions using high-resolution tiling arrays

    OpenAIRE

    Voorhies, Mark; Foo, Catherine K; Sil, Anita

    2011-01-01

    Abstract Background The fungal pathogen Histoplasma capsulatum is thought to be the most common cause of fungal respiratory infections in immunocompetent humans, yet little is known about its biology. Here we provide the first genome-wide studies to experimentally validate its genome annotation. A functional interrogation of the Histoplasma genome provides critical support for continued investigation into the biology and pathogenesis of H. capsulatum and related fungi. Results We employed a t...

  15. CEACAM3: ein neuartiger phagozytischer Rezeptor der angeborenen Immunantwort zur Erkennung human-spezifischer Pathogene

    OpenAIRE

    Schmitter, Tim

    2006-01-01

    Eine Infektion durch das ausschließlich human-spezifische Pathogen Neisseria gonorrhoeae manifestiert sich bei einer symptomatischen Kolonisierung in der sog. Gonorrhö, einer venerischen Erkrankung, die durch akute Inflammation des befallenen Gewebes und durch die massive Infiltration von Granulozyten charakterisiert ist. Die Gonokokken können im Verlauf einer symptomatischen Infektion über ihre OpaCEA-Adhäsine mit CEACAM Proteinen unterschiedlicher Wirtszellen interagieren. In der vorliegend...

  16. Rhizobium pusense is the main human pathogen in the genus Agrobacterium/Rhizobium.

    Science.gov (United States)

    Aujoulat, F; Marchandin, H; Zorgniotti, I; Masnou, A; Jumas-Bilak, E

    2015-05-01

    Rhizobium pusense was recently described after isolation from the rhizosphere of chickpea. Multilocus sequence-based analysis of clinical isolates identified as Agrobacterium (Rhizobium) radiobacter demonstrated that R. pusense is the main human pathogen within Agrobacterium (Rhizobium) spp. Clinical microbiology of Agrobacterium (Rhizobium) should be considered in the light of recent taxonomic changes. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. TRANSMISSION ROUTES OF NOROVIRUSES, EMERGING HUMAN PATHOGENS IN FOOD “NORISK”

    OpenAIRE

    Mathijs, E; Stals, A; Denayer, S; Baert, L; Bottledoorn, N; Vancoillie, E; Daube, Georges; Dierick, K; Herman, Lieve; Thiry, Etienne; Uyttendaele, Mieke

    2011-01-01

    A. Context Noroviruses are pathogens causing gastroenteritis and infections result in typical symptoms such as abdominal cramps, fever, watery diarrhea and other symptoms such as headaches, chills and general myalgias, which usually last for 2 to 3 days. The illness is self-limiting in most cases. The NV genus contains 5 genogroups whereby genogroup I and II (GI and GII) comprise most of the human infective NV genotypes. Bovine and murine NV are classified respectively in genogroup III (GI...

  18. The Genome of the Basidiomycetous Yeast and Human Pathogen Cryptococcus neoformans

    OpenAIRE

    Loftus, Brendan J.; Fung, Eula; Roncaglia, Paola; Rowley, Don; Amedeo, Paolo; Bruno, Dan; Vamathevan, Jessica; Miranda, Molly; Anderson, Iain J.; Fraser, James A.; Allen, Jonathan E.; Bosdet, Ian E.; Brent, Michael R.; Chiu, Readman; Doering, Tamara L.

    2005-01-01

    Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its ~20-megabase genome, which contains ~6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions. The presence of these transposons may drive karyotype i...

  19. A general framework for estimating the relative pathogenicity of human genetic variants

    Science.gov (United States)

    Kircher, Martin; Witten, Daniela M.; Jain, Preti; O’Roak, Brian J.; Cooper, Gregory M.; Shendure, Jay

    2014-01-01

    Our capacity to sequence human genomes has exceeded our ability to interpret genetic variation. Current genomic annotations tend to exploit a single information type (e.g. conservation) and/or are restricted in scope (e.g. to missense changes). Here, we describe Combined Annotation Dependent Depletion (CADD), a framework that objectively integrates many diverse annotations into a single, quantitative score. We implement CADD as a support vector machine trained to differentiate 14.7 million high-frequency human derived alleles from 14.7 million simulated variants. We pre-compute “C-scores” for all 8.6 billion possible human single nucleotide variants and enable scoring of short insertions/deletions. C-scores correlate with allelic diversity, annotations of functionality, pathogenicity, disease severity, experimentally measured regulatory effects, and complex trait associations, and highly rank known pathogenic variants within individual genomes. The ability of CADD to prioritize functional, deleterious, and pathogenic variants across many functional categories, effect sizes and genetic architectures is unmatched by any current annotation. PMID:24487276

  20. A human pathogenic bacterial infection model using the two-spotted cricket, Gryllus bimaculatus.

    Science.gov (United States)

    Kochi, Yuto; Miyashita, Atsushi; Tsuchiya, Kohsuke; Mitsuyama, Masao; Sekimizu, Kazuhisa; Kaito, Chikara

    2016-08-01

    Invertebrate animal species that can withstand temperatures as high as 37°C, the human body temperature, are limited. In the present study, we utilized the two-spotted cricket, Gryllus bimaculatus, which lives in tropical and subtropical regions, as an animal model of human pathogenic bacterial infection. Injection of Pseudomonas aeruginosa or Staphylococcus aureus into the hemolymph killed crickets. Injected P. aeruginosa or S. aureus proliferated in the hemolymph until the cricket died. The ability of these pathogenic bacteria to kill the crickets was blocked by the administration of antibiotics. S. aureus gene-knockout mutants of virulence factors, including cvfA, agr and srtA, exhibited decreased killing ability compared with the parent strain. The dose at which 50% of crickets were killed by P. aeruginosa or S. aureus was not decreased at 37°C compared with that at 27°C. Injection of Listeria monocytogenes, which upregulates toxin expression at 37°C, killed crickets, and the dose at which 50% of crickets were killed was decreased at 37°C compared with that at 27°C. These findings suggest that the two-spotted cricket is a useful model animal for evaluating the virulence properties of various human pathogenic bacteria at variable temperature including 37°C. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Detection of diarrhoeal pathogens in human faeces using an automated, robotic platform.

    Science.gov (United States)

    Jex, Aaron R; Stanley, Keith K; Lo, William; Littman, Rachael; Verweij, Jaco J; Campbell, Bronwyn E; Nolan, Matthew J; Pangasa, Aradhana; Stevens, Melita A; Haydon, Shane; Gasser, Robin B

    2012-02-01

    Infectious diarrhoeal diseases represent a major socio-economic burden to humans, and are linked to a range of pathogens, including viruses, bacteria and protists. The accurate detection of such pathogens is central to control. However, detection often relies on methods that have limited diagnostic sensitivity and specificity. Here, we assessed an automated, robotic platform for the simultaneous detection of eight major pathogens associated with infectious diarrhoea. Genomic DNA samples (n = 167) from faeces from humans with diarrhoea and diagnosed as cryptosporidiosis, and 100 uninfected control subjects, were tested for adenovirus 40/41, norovirus, Clostridium difficile, Campylobacter, Salmonella, Shigella, Cryptosporidium and Giardia by multiplexed-tandem PCR, and also characterized by single-strand conformation polymorphism analysis (SSCP) and selective sequencing. All 167 samples tested positive for Cryptosporidium, five for adenovirus 40/41, four for Campylobacter, three for C. difficile and seven for Shigella spp., with no false positive results for any assay. The automated PCR exhibited a high sensitivity, with humans. This platform requires little molecular biological expertise and is well suited to various diagnostic facilities and settings. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Ion mobility spectrometry for microbial volatile organic compounds: a new identification tool for human pathogenic bacteria.

    Science.gov (United States)

    Jünger, Melanie; Vautz, Wolfgang; Kuhns, Martin; Hofmann, Lena; Ulbricht, Siobhán; Baumbach, Jörg Ingo; Quintel, Michael; Perl, Thorsten

    2012-03-01

    Presently, 2 to 4 days elapse between sampling at infection suspicion and result of microbial diagnostics. This delay for the identification of pathogens causes quite often a late and/or inappropriate initiation of therapy for patients suffering from infections. Bad outcome and high hospitalization costs are the consequences of these currently existing limited pathogen identification possibilities. For this reason, we aimed to apply the innovative method multi-capillary column-ion mobility spectrometry (MCC-IMS) for a fast identification of human pathogenic bacteria by determination of their characteristic volatile metabolomes. We determined volatile organic compound (VOC) patterns in headspace of 15 human pathogenic bacteria, which were grown for 24 h on Columbia blood agar plates. Besides MCC-IMS determination, we also used thermal desorption-gas chromatography-mass spectrometry measurements to confirm and evaluate obtained MCC-IMS data and if possible to assign volatile compounds to unknown MCC-IMS signals. Up to 21 specific signals have been determined by MCC-IMS for Proteus mirabilis possessing the most VOCs of all investigated strains. Of particular importance is the result that all investigated strains showed different VOC patterns by MCC-IMS using positive and negative ion mode for every single strain. Thus, the discrimination of investigated bacteria is possible by detection of their volatile organic compounds in the chosen experimental setup with the fast and cost-effective method MCC-IMS. In a hospital routine, this method could enable the identification of pathogens already after 24 h with the consequence that a specific therapy could be initiated significantly earlier.

  3. Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

    Directory of Open Access Journals (Sweden)

    Andreas eHofmann

    2014-05-01

    Full Text Available In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system or via agricultural soil amended with spiked organic fertilizers (soil system. In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4x10CFU/ml in the axenic system or 4x105CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in

  4. Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

    Science.gov (United States)

    Hofmann, Andreas; Fischer, Doreen; Hartmann, Anton; Schmid, Michael

    2014-01-01

    In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system) or via agricultural soil amended with spiked organic fertilizers (soil system). In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH) was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4 × 10 CFU/ml in the axenic system or 4 × 105 CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in some cases

  5. Environmental Transport of Emerging Human-Pathogenic Cryptosporidium Species and Subtypes through Combined Sewer Overflow and Wastewater.

    Science.gov (United States)

    Huang, Chengchen; Hu, Yue; Wang, Lin; Wang, Yuanfei; Li, Na; Guo, Yaqiong; Feng, Yaoyu; Xiao, Lihua

    2017-08-15

    The environmental transport of Cryptosporidium spp. through combined sewer overflow (CSO) and the occurrence of several emerging human-pathogenic Cryptosporidium species in developing countries remain unclear. In this study, we collected 40 CSO samples and 40 raw wastewater samples from Shanghai, China, and examined them by PCR and DNA sequencing for Cryptosporidium species (targeting the small subunit rRNA gene) and Giardia duodenalis (targeting the triosephosphate isomerase, β-giardin, and glutamate dehydrogenase genes) and Enterocytozoon bieneusi (targeting the ribosomal internal transcribed spacer) genotypes. Human-pathogenic Cryptosporidium species were further subtyped by sequence analysis of the 60-kDa glycoprotein gene, with additional multilocus sequence typing on the emerging zoonotic pathogen Cryptosporidium ubiquitum. Cryptosporidium spp., G. duodenalis , and E. bieneusi were detected in 12 and 15, 33 and 32, and 37 and 40 CSO and wastewater samples, respectively, including 10 Cryptosporidium species, 3 G. duodenalis assemblages, and 8 E. bieneusi genotypes. In addition to Cryptosporidium hominis and Cryptosporidium parvum , two new pathogens identified in industrialized nations, C. ubiquitum and Cryptosporidium viatorum , were frequently detected. The two novel C. ubiquitum subtype families identified appeared to be genetic recombinants of known subtype families. Similarly, the dominant group 1 E. bieneusi genotypes and G. duodenalis subassemblage AII are known human pathogens. The similar distribution of human-pathogenic Cryptosporidium species and E. bieneusi and G. duodenalis genotypes between wastewater and CSO samples reaffirms that storm overflow is potentially a significant contamination source of pathogens in surface water. The frequent identification of C. ubiquitum and C. viatorum in urban wastewater suggests that these newly identified human pathogens may be endemic in China. IMPORTANCE Cryptosporidium spp., Giardia duodenalis , and

  6. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....

  7. Progress in rapid detection and identification of unknown human and agricultural pathogens

    International Nuclear Information System (INIS)

    Barnes, T; Holzrichter, J F; Milanovich, F P

    1999-01-01

    contained in pathogen systems, such as their full genomic information, can be very helpful in identifying malevolent users. In addition, it is undoubtedly true that an understanding of replication and human or other sensitivity to pathogens will improve our medical understanding of human health in general

  8. Antifungal activity of different neem leaf extracts and the nimonol against some important human pathogens

    Directory of Open Access Journals (Sweden)

    D.A Mahmoud

    2011-09-01

    Full Text Available This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl acetate extracts from neem leaves on growth of some human pathogens (Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida albicans and Microsporum gypseum in vitro. Different concentrations (5, 10, 15 and 20% prepared from these extracts inhibited the growth of the test pathogens and the effect gradually increased with concentration. The 20% ethyl acetate extract gave the strongest inhibition compared with the activity obtained by the same concentration of the other extracts. High Performance Liquid Chromatography (HPLC analysis of ethyl acetate extract showed the presence of a main component (nimonol which was purified and chemically confirmed by Nuclear Magnetic Resonance (NMR spectroscopic analysis. The 20% ethyl acetate extract lost a part of its antifungal effect after pooling out the nimonol and this loss in activity was variable on test pathogens. The purified nimonol as a separate compound did not show any antifungal activity when assayed against all the six fungal pathogens.

  9. Investigating the Antimicrobial Bioactivity of Cyano bacterial Extracts on Some Plant and Human Pathogens

    International Nuclear Information System (INIS)

    El-Semary, N.A.; Osman, M.E.; Ahmed, A.S.; Botros, H.W.; Farag, A.T.

    2014-01-01

    The search for broad spectrum antimicrobial agents against microbial pathogens, as the available bioactive compounds, has decreasing efficacy and the multidrug resistance trait is spreading among pathogens. Accordingly, the study was carried out to investigate the antimicrobial bioactivity of extracts derived from a cyano bacterial strain from Egypt. The solvents used were diethyl ether, chloroform and methanol. The antimicrobial bioassay of the lipophilic fraction dissolved in diethyl ether of Synechococcus spp. (isolated from Wadi El-Natroun, Egypt) showed the highest broad spectrum bioactivity as it inhibited the growth of both plant and human pathogens. The extract was also effective on the filamentous plant pathogenic fungi Aspergillus flavus and Aspergillus niger. The effects of incubation periods, growth media and pH values on both growth and antimicrobial activity of Synechococcus spp. were investigated. Chu medium was the medium that gave the highest growth followed by BG11 medium then Oscillatoria medium and all these three media showed antibacterial activities but only BG11 showed both antibacterial and antifungal activities after 18 days of incubation. The pH value 10 proved to be the best for growth and antimicrobial activities of Synechococcus spp. in BG11 medium

  10. Exploring the Unique N-Glycome of the Opportunistic Human Pathogen Acanthamoeba*

    Science.gov (United States)

    Schiller, Birgit; Makrypidi, Georgia; Razzazi-Fazeli, Ebrahim; Paschinger, Katharina; Walochnik, Julia; Wilson, Iain B. H.

    2012-01-01

    Glycans play key roles in host-pathogen interactions; thus, knowing the N-glycomic repertoire of a pathogen can be helpful in deciphering its methods of establishing and sustaining a disease. Therefore, we sought to elucidate the glycomic potential of the facultative amoebal parasite Acanthamoeba. This is the first study of its asparagine-linked glycans, for which we applied biochemical tools and various approaches of mass spectrometry. An initial glycomic screen of eight strains from five genotypes of this human pathogen suggested, in addition to the common eukaryotic oligomannose structures, the presence of pentose and deoxyhexose residues on their N-glycans. A more detailed analysis was performed on the N-glycans of a genotype T11 strain (4RE); fractionation by HPLC and tandem mass spectrometric analyses indicated the presence of a novel mannosylfucosyl modification of the reducing terminal core as well as phosphorylation of mannose residues, methylation of hexose and various forms of pentosylation. The largest N-glycan in the 4RE strain contained two N-acetylhexosamine, thirteen hexose, one fucose, one methyl, and two pentose residues; however, in this and most other strains analyzed, glycans with compositions of Hex8–9HexNAc2Pnt0–1 tended to dominate in terms of abundance. Although no correlation between pathogenicity and N-glycan structure can be proposed, highly unusual structures in this facultative parasite can be found which are potential virulence factors or therapeutic targets. PMID:23139421

  11. What's the risk? Identifying potential human pathogens within grey-headed flying foxes faeces.

    Science.gov (United States)

    Henry, Rebekah; Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T

    2018-01-01

    Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals.

  12. What’s the risk? Identifying potential human pathogens within grey-headed flying foxes faeces

    Science.gov (United States)

    Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

    2018-01-01

    Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

  13. Identifying pathogenicity of human variants via paralog-based yeast complementation.

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2017-05-01

    Full Text Available To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays. We tested over 1,000 paralogous human-yeast gene pairs for complementation, yielding 34 complementation relationships, of which 33 (97% were novel. We found that paralog-based assays identified disease variants with success on par with that of orthology-based assays. Combining all homology-based assay results, we found that complementation can often identify pathogenic variants outside the homologous sequence region, presumably because of global effects on protein folding or stability. Within our search space, paralogy-based complementation more than doubled the number of human disease genes with a yeast-based complementation assay for disease variation.

  14. Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1.

    Science.gov (United States)

    Koning, Nathalie; Kessen, Sabine F M; Van Der Voorn, J Patrick; Appelmelk, Ben J; Jeurink, Prescilla V; Knippels, Leon M J; Garssen, Johan; Van Kooyk, Yvette

    2015-01-01

    Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on dendritic cell (DC) and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastrointestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.

  15. A molecular biological protocol to distinguish potentially human pathogenic Stenotrophomonas maltophilia from plant-associated Stenotrophomonas rhizophila

    NARCIS (Netherlands)

    Ribbeck-Busch, K.; Roder, A.; Hasse, D.; De Boer, W.; Martinez, J.L.; Hagemann, M.; Berg, G.

    2005-01-01

    In recent years, the importance of the Gram-negative bacterium Stenotrophomonas as an opportunistic pathogen as well as in biotechnology has increased. The aim of the present study was to develop new methods for distinguishing between strains closely related to the potentially human pathogenic

  16. Contamination of poultry flocks by the human pathogen Campylobacter spp. and strategies to reduce its prevalence at the farm level

    Directory of Open Access Journals (Sweden)

    Théwis A.

    2008-01-01

    Full Text Available Enteric Campylobacter spp. bacteria are human pathogens that frequently contaminate poultry flocks. Consumption of products from poultry origin may then lead to acute bacterial enteritis called campylobacteriosis of which prevalence is increasing for about ten years in Europe. This review summarizes Campylobacter epidemiological data, risk factors for contamination in poultry flocks and conceivable strategies to control this pathogen.

  17. Survival of pathogenic and lactobacilli species of fermented olives during simulated human digestion

    Directory of Open Access Journals (Sweden)

    Francisco Noé eArroyo López

    2014-10-01

    Full Text Available The present survey uses a dynamic gastric and small intestinal model to assess the survival of one pathogenic (Escherichia coli O157:H7 EDL 933 and three lactobacilli bacteria with probiotic potential (Lactobacillus rhamnosus GG, Lactobacillus pentosus TOMC-LAB2 and Lactobacillus pentosus TOMC-LAB4 during their passage through the human gastrointestinal tract using fermented olives as the food matrix. The data showed that the survival of the E. coli strain in the stomach and duodenum was very low, while its transit through the distal parts (jejunum and ileum resulted in an increase in the pathogen population. The production of Shiga toxins by this enterohemorrhagic microorganism in the ileal effluents of the in vitro system was too low to be detected by ELISA assays. On the contrary, the three lactobacilli species assayed showed a considerable resistance to the gastric digestion, but not to the intestinal one, which affected their survival, and was especially evident in the case of both L. pentosus strains. In spite of this, high population levels for all assayed microorganisms were recovered at the end of the gastrointestinal passage. The results obtained in the present study show the potential use of table olives as a vehicle of beneficial microorganisms to the human body, as well as the need for good hygienic practices on the part of olive manufacturers in order to avoid the possibility of contamination by food-borne pathogens.

  18. Survival of pathogenic and lactobacilli species of fermented olives during simulated human digestion.

    Science.gov (United States)

    Arroyo-López, Francisco N; Blanquet-Diot, Stéphanie; Denis, Sylvain; Thévenot, Jonathan; Chalancon, Sandrine; Alric, Monique; Rodríguez-Gómez, Francisco; Romero-Gil, Verónica; Jiménez-Díaz, Rufino; Garrido-Fernández, Antonio

    2014-01-01

    The present survey uses a dynamic gastric and small intestinal model to assess the survival of one pathogenic (Escherichia coli O157:H7 EDL 933) and three lactobacilli bacteria with probiotic potential (Lactobacillus rhamnosus GG, L. pentosus TOMC-LAB2, and L. pentosus TOMC-LAB4) during their passage through the human gastrointestinal tract using fermented olives as the food matrix. The data showed that the survival of the E. coli strain in the stomach and duodenum was very low, while its transit through the distal parts (jejunum and ileum) resulted in an increase in the pathogen population. The production of Shiga toxins by this enterohemorrhagic microorganism in the ileal effluents of the in vitro system was too low to be detected by ELISA assays. On the contrary, the three lactobacilli species assayed showed a considerable resistance to the gastric digestion, but not to the intestinal one, which affected their survival, and was especially evident in the case of both L. pentosus strains. In spite of this, high population levels for all assayed microorganisms were recovered at the end of the gastrointestinal passage. The results obtained in the present study show the potential use of table olives as a vehicle of beneficial microorganisms to the human body, as well as the need for good hygienic practices on the part of olive manufacturers in order to avoid the possibility of contamination by food-borne pathogens.

  19. Pathogens of Food Animals: Sources, Characteristics, Human Risk, and Methods of Detection.

    Science.gov (United States)

    Logue, Catherine M; Barbieri, Nicolle L; Nielsen, Daniel W

    Pathogens associated with food production (livestock) animals come in many forms causing a multitude of disease for humans. For the purpose of this review, these infectious agents can be divided into three broad categories: those that are associated with bacterial disease, those that are associated with viruses, and those that are parasitic in nature. The goal of this chapter is to provide the reader with an overview of the most common pathogens that cause disease in humans through exposure via the food chain and the consequence of this exposure as well as risk and detection methods. We have also included a collection of unusual pathogens that although rare have still caused disease, and their recognition is warranted in light of emerging and reemerging diseases. These provide the reader an understanding of where the next big outbreak could occur. The influence of the global economy, the movement of people, and food makes understanding production animal-associated disease paramount to being able to address new diseases as they arise. © 2017 Elsevier Inc. All rights reserved.

  20. Cladophora (Chlorophyta) spp. harbor human bacterial pathogens in nearshore water of Lake Michigan

    Science.gov (United States)

    Ishii, S.; Yan, T.; Shively, D.A.; Byappanahalli, M.N.; Whitman, R.L.; Sadowsky, M.J.

    2006-01-01

    Cladophora glomerata, a macrophytic green alga, is commonly found in the Great Lakes, and significant accumulations occur along shorelines during the summer months. Recently, Cladophora has been shown to harbor high densities of the fecal indicator bacteria Escherichia coli and enterococci. Cladophora may also harbor human pathogens; however, until now, no studies to address this question have been performed. In the present study, we determined whether attachedCladophora, obtained from the Lake Michigan and Burns Ditch (Little Calumet River, Indiana) sides of a breakwater during the summers of 2004 and 2005, harbored the bacterial pathogens Shiga toxin-producing Escherichia coli (STEC),Salmonella, Shigella, and Campylobacter. The presence of potential pathogens and numbers of organisms were determined by using cultural methods and by using conventional PCR, most-probable-number PCR (MPN-PCR), and quantitative PCR (QPCR) performed with genus- and toxin-specific primers and probes. WhileShigella and STEC were detected in 100% and 25%, respectively, of the algal samples obtained near Burns Ditch in 2004, the same pathogens were not detected in samples collected in 2005. MPN-PCR and QPCR allowed enumeration of Salmonella in 40 to 80% of the ditch- and lakeside samples, respectively, and the densities were up to 1.6 × 103 cells per g Cladophora. Similarly, these PCR methods allowed enumeration of up to 5.4 × 102 Campylobacter cells/gCladophora in 60 to 100% of lake- and ditchside samples. The Campylobacterdensities were significantly higher (P pathogenic bacteria in Lake Michigan and that the association of these bacteria with Cladophora warrants additional studies to assess the potential health impact on beach users.

  1. Antibacterial screening of traditional herbal plants and standard antibiotics against some human bacterial pathogens.

    Science.gov (United States)

    Awan, Uzma Azeem; Andleeb, Saiqa; Kiyani, Ayesha; Zafar, Atiya; Shafique, Irsa; Riaz, Nazia; Azhar, Muhammad Tehseen; Uddin, Hafeez

    2013-11-01

    Chloroformic and isoamyl alcohol extracts of Cinnnamomum zylanicum, Cuminum cyminum, Curcuma long Linn, Trachyspermum ammi and selected standard antibiotics were investigated for their in vitro antibacterial activity against six human bacterial pathogens. The antibacterial activity was evaluated and based on the zone of inhibition using agar disc diffusion method. The tested bacterial strains were Streptococcus pyogenes, Staphylococcus epidermidis, Klebsiella pneumonia, Staphylococcus aurues, Serratia marcesnces, and Pseudomonas aeruginosa. Ciprofloxacin showed highly significant action against K. pneumonia and S. epidermidis while Ampicillin and Amoxicillin indicated lowest antibacterial activity against tested pathogens. Among the plants chloroform and isoamyl alcohol extracts of C. cyminum, S. aromaticum and C. long Linn had significant effect against P. aeruginosa, S. marcesnces and S. pyogenes. Comparison of antibacterial activity of medicinal herbs and standard antibiotics was also recorded via activity index. Used medicinal plants have various phytochemicals which reasonably justify their use as antibacterial agent.

  2. Rapid Synthesis of Gold Nanoparticles from Quercus incana and Their Antimicrobial Potential against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Rizwana Sarwar

    2017-01-01

    Full Text Available In current study, bioreduction of tetrachloroauric acid (HAuCl4·3H2O was carried out using leaves extract of Quercus incana for nanoparticle synthesis. The nanoparticles were characterized by ultraviolet visible spectrum (UV, Fourier-transform infrared (FT-IR, and transmission electron microscopy (TEM analysis. The gold nanoparticles (GNPs were generally clumpy agglomerates of polydispersed particles, with an average size in the range 5.5–10 nm. The Gas chromatography–mass spectrometry (GC–MS qualitative analysis and FT-IR data supported the presence of bioactive compounds, which are responsible for the metal reduction and nanoparticles stabilization. The biocompatibility of synthesized GNPs was evaluated via antibacterial activity by using human bacterial pathogens. The results showed that synthesized GNPs showed enhanced antibacterial activity against all bacterial pathogens.

  3. Agathobaculum butyriciproducens gen. nov.  sp. nov., a strict anaerobic, butyrate-producing gut bacterium isolated from human faeces and reclassification of Eubacterium desmolans as Agathobaculum desmolans comb. nov.

    Science.gov (United States)

    Ahn, Sharon; Jin, Tae-Eun; Chang, Dong-Ho; Rhee, Moon-Soo; Kim, Hyun Ju; Lee, Sang Jun; Park, Doo-Sang; Kim, Byoung-Chan

    2016-09-01

    A novel bacterial strain, SR79T, was isolated from a Korean faecal sample and characterized using a polyphasic approach. SR79T was found to be a strictly anaerobic, Gram-stain-positive, non-spore-forming, non-motile, catalase- and oxidase-negative short rod with no flagella. SR79T grew optimally at 37 °C in the presence of 0.5 % (w/v) NaCl at pH 7. The NaCl range for growth was 0-1 % (w/v). The isolate produced butyric acid (>18  mM) as a major end product. A phylogenetic analysis based on 16S rRNA gene sequences revealed that the most closely related type strains were Eubacteriumdesmolans ATCC 43058T and Butyricicoccus pullicaecorum 25-3T (96.4 and 96.0 % similarity, respectively). The DNA G+C content was determined to be 52.9 mol%. The major cellular fatty acids (>10 %) were C16 : 0, C18 : 1cis-9, C19 : 1 cyc 9,10 and C14 : 0. Meso-diaminopimelic acid was present in the cell wall peptidoglycan and the cell wall hydrolysates contained ribose, glucose and galactose. The 16S rRNA gene sequence similarity, phylogenetic analysis, chemotaxonomic and phenotypic characteristics allowed differentiation of SR79T, which represents a novel species of a new genus within the family Ruminococcaceae, for which the name Agathobaculum butyriciproducens gen. nov. sp. nov. is proposed. The type strain is SR79T (=KCTC 15532T=DSM 100391T). Based on the results of this study, it is also proposed to transfer Eubacteriumdesmolans to this new genus, as Agathobaculum desmolans comb. nov. The type strain of Agathobaculum desmolans is ATCC 43058T (=CCUG 27818T).

  4. Detection of human bacterial pathogens in ticks collected from Louisiana black bears (Ursus americanus luteolus).

    Science.gov (United States)

    Leydet, Brian F; Liang, Fang-Ting

    2013-04-01

    There are 4 major human-biting tick species in the northeastern United States, which include: Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, and Ixodes scapularis. The black bear is a large mammal that has been shown to be parasitized by all the aforementioned ticks. We investigated the bacterial infections in ticks collected from Louisiana black bears (Ursus americanus subspecies luteolus). Eighty-six ticks were collected from 17 black bears in Louisiana from June 2010 to March 2011. All 4 common human-biting tick species were represented. Each tick was subjected to polymerase chain reaction (PCR) targeting select bacterial pathogens and symbionts. Bacterial DNA was detected in 62% of ticks (n=53). Rickettsia parkeri, the causative agent of an emerging spotted fever group rickettsiosis, was identified in 66% of A. maculatum, 28% of D. variabilis, and 11% of I. scapularis. The Lyme disease bacterium, Borrelia burgdorferi, was detected in 2 I. scapularis, while one A. americanum was positive for Borrelia bissettii, a putative human pathogen. The rickettsial endosymbionts Candidatus Rickettsia andeanae, rickettsial endosymbiont of I. scapularis, and Rickettsia amblyommii were detected in their common tick hosts at 21%, 39%, and 60%, respectively. All ticks were PCR-negative for Anaplasma phagocytophilum, Ehrlichia spp., and Babesia microti. This is the first reported detection of R. parkeri in vector ticks in Louisiana; we also report the novel association of R. parkeri with I. scapularis. Detection of both R. parkeri and B. burgdorferi in their respective vectors in Louisiana demands further investigation to determine potential for human exposure to these pathogens. Copyright © 2013 Elsevier GmbH. All rights reserved.

  5. Prevalence of Tick-Borne Pathogens in Hard Ticks That Attacked Human Hosts in Eastern Siberia

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    Maxim A. Khasnatinov

    2017-12-01

    Full Text Available The aim of this study was to evaluate the risk of tick-borne infections in humans. The prevalence of 4 tick-borne pathogens was studied in the population of Ixodid ticks attacking human hosts in Irkutsk city and neighbouring territories from 2007 to 2017. Methods and Results: In total, 46,357 tick specimens detached from bitten people were analyzed. The antigen of tick-borne encephalitis virus (TBEV was detected in each tick individually by ELISA assay using a commercial kit for the envelope protein E of TBEV. Total RNA and DNA were extracted from ticks using a RiboPrep kit. Reverse transcription was performed using a Reverta-L kit and RNA\\DNA of TBEV; B. burgdorferi sensu lato, A. phagocytophylum and Ehrlichia muris\\E. chaffeensis were detected using a real-time multiplex PCR kit. In total, during 8 years of observations, I. persulcatus caused approximately 86% of bites, Dermacentor sp. 13.95 %, and H. concinna 0.05 %. The most prevalent tick-borne pathogen in I. persulcatus ticks was Lyme disease agent B. burgdorferi sensu lato, which was detected in 12±6.5% of specimens annually. A. phagocytophilum and Ehrlichia sp. were detected in 7.8±2.7% and 4.6±1.5% of specimens, respectively. TBEV was present in 1±0.7% of I. persulcatus. Conclusion: I. persulcatus remains the most important vector of tick-borne diseases to humans in Eastern Siberia. D. nuttalli and D. silvarum are much less aggressive to humans and are less infected with major tick-borne pathogens. H. concinna does not play any significant role as a disease vector. However, a rigorous analysis of TBEV spread in the Dermacentor sp. population is necessary.

  6. Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens.

    Science.gov (United States)

    Ismail, Ashrafali M; Cui, Tiange; Dommaraju, Kalpana; Singh, Gurdeep; Dehghan, Shoaleh; Seto, Jason; Shrivastava, Susmita; Fedorova, Nadia B; Gupta, Neha; Stockwell, Timothy B; Madupu, Ramana; Heim, Albert; Kajon, Adriana E; Romanowski, Eric G; Kowalski, Regis P; Malathi, Jambulingam; Therese, Kuzhanthai L; Madhavan, Hajib Narahari; Zhang, Qiwei; Ferreyra, Leonardo J; Jones, Morris S; Rajaiya, Jaya; Dyer, David W; Chodosh, James; Seto, Donald

    2018-02-07

    Human adenoviruses (HAdVs) are uniquely important "model organisms" as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to "one-time" appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population.

  7. Geometrical optimization for strictly localized structures

    Science.gov (United States)

    Mo, Yirong

    2003-07-01

    Recently we proposed the block localized wavefunction (BLW) approach which takes the advantages of valence bond theory and molecular orbital theory and defines the wavefunctions for resonance structures based on the assumption that all electrons and orbitals are partitioned into a few subgroups. In this work, we implement the geometrical optimization of the BLW method based on the algorithm proposed by Gianinetti and coworkers. Thus, we can study the conjugation effect on not only the molecular stability, but also the molecular geometry. With this capability, the π conjugation effect in trans-polyenes C2nH2n+2 (n=2-5) as well as in formamide and its analogs are studied by optimizing their delocalized and strictly localized forms with the 6-31G(d) and 6-311+G(d,p) basis sets. Although it has been well presumed that the π resonance shortens the single bonds and lengthens the double bonds with the delocalization of π electrons across the whole line in polyenes, our optimization of the strictly localized structures quantitatively shows that when the conjugation effect is "turned off," the double bond lengths will be identical to the CC bond length in ethylene and the single Csp2-Csp2 bond length will be about 1.513-1.517 Å. In agreement with the classical Hückel theory, the resonance energies in polyenes are approximately in proportion to the number of double bonds. Similarly, resonance is responsible not only for the planarity of formamide, thioformamide, and selenoformamide, but also for the lengthening of the CX (X=O,S,Se) double bond and the shortening of the CN bonds. Although it is assumed that the CX bond polarization decreases in the order of O>S>Se, the π electronic delocalization increases in the opposite order, i.e., formamide

  8. From Regular to Strictly Locally Testable Languages

    Directory of Open Access Journals (Sweden)

    Stefano Crespi Reghizzi

    2011-08-01

    Full Text Available A classical result (often credited to Y. Medvedev states that every language recognized by a finite automaton is the homomorphic image of a local language, over a much larger so-called local alphabet, namely the alphabet of the edges of the transition graph. Local languages are characterized by the value k=2 of the sliding window width in the McNaughton and Papert's infinite hierarchy of strictly locally testable languages (k-slt. We generalize Medvedev's result in a new direction, studying the relationship between the width and the alphabetic ratio telling how much larger the local alphabet is. We prove that every regular language is the image of a k-slt language on an alphabet of doubled size, where the width logarithmically depends on the automaton size, and we exhibit regular languages for which any smaller alphabetic ratio is insufficient. More generally, we express the trade-off between alphabetic ratio and width as a mathematical relation derived from a careful encoding of the states. At last we mention some directions for theoretical development and application.

  9. Epidemiology of pathogenic enterobacteria in humans, livestock, and peridomestic rodents in rural Madagascar.

    Directory of Open Access Journals (Sweden)

    DeAnna C Bublitz

    Full Text Available BACKGROUND: Among the families of enteric bacteria are globally important diarrheal agents. Despite their potential for zoonotic and environmental transmission, few studies have examined the epidemiology of these pathogens in rural systems characterized by extensive overlap among humans, domesticated and peridomestic animals. We investigated patterns of infection with Enterotoxigenic Escherichia coli, Shigella spp., Salmonella enterica, Vibrio cholerae, and Yersinia spp. (enterocolitica, and pseudotuberculosis in Southeastern Madagascar where the potential for the aforementioned interactions is high. In this pilot project we conducted surveys to examine behaviors potentially associated with risk of infection and if infection with specific enterobacteria species was associated with diarrheal disease. METHODOLOGY/PRINCIPAL FINDINGS: PCR was conducted on DNA from human, livestock, and rodent fecal samples from three villages. Overall, human prevalence was highest (77%, followed by rodents (51% and livestock (18%. Rodents were ∼2.8 times more likely than livestock to carry one of the bacteria. The incidence of individual species varied between villages, with the observation that, E. coli and Shigella spp. were consistently associated with co-infections. As an aggregate, there was a significant risk of infection linked to a water source in one village. Individually, different pathogens were associated with certain behaviors, including: those who had used medication, experienced diarrhea in the past four weeks, or do not use toilets. CONCLUSIONS/SIGNIFICANCE: Different bacteria were associated with an elevated risk of infection for various human activities or characteristics. Certain bacteria may also predispose people to co-infections. These data suggest that a high potential for transmission among these groups, either directly or via contaminated water sources. As these bacteria were most prevalent in humans, it is possible that they are

  10. Multilocus Sequence Typing of Borrelia burgdorferi Suggests Existence of Lineages with Differential Pathogenic Properties in Humans

    Science.gov (United States)

    Hanincova, Klara; Mukherjee, Priyanka; Ogden, Nicholas H.; Margos, Gabriele; Wormser, Gary P.; Reed, Kurt D.; Meece, Jennifer K.; Vandermause, Mary F.; Schwartz, Ira

    2013-01-01

    The clinical manifestations of Lyme disease, caused by Borrelia burgdorferi, vary considerably in different patients, possibly due to infection by strains with varying pathogenicity. Both rRNA intergenic spacer and ospC typing methods have proven to be useful tools for categorizing B. burgdorferi strains that vary in their tendency to disseminate in humans. Neither method, however, is suitable for inferring intraspecific relationships among strains that are important for understanding the evolution of pathogenicity and the geographic spread of disease. In this study, multilocus sequence typing (MLST) was employed to investigate the population structure of B. burgdorferi recovered from human Lyme disease patients. A total of 146 clinical isolates from patients in New York and Wisconsin were divided into 53 sequence types (STs). A goeBURST analysis, that also included previously published STs from the northeastern and upper Midwestern US and adjoining areas of Canada, identified 11 major and 3 minor clonal complexes, as well as 14 singletons. The data revealed that patients from New York and Wisconsin were infected with two distinct, but genetically and phylogenetically closely related, populations of B. burgdorferi. Importantly, the data suggest the existence of B. burgdorferi lineages with differential capabilities for dissemination in humans. Interestingly, the data also indicate that MLST is better able to predict the outcome of localized or disseminated infection than is ospC typing. PMID:24069170

  11. 7 CFR 28.404 - Strict Low Middling Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Color. 28.404 Section 28.404... for the Color Grade of American Upland Cotton § 28.404 Strict Low Middling Color. Strict Low Middling Color is color which is within the range represented by a set of samples in the custody of the United...

  12. 7 CFR 28.406 - Strict Good Ordinary Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Good Ordinary Color. 28.406 Section 28.406... for the Color Grade of American Upland Cotton § 28.406 Strict Good Ordinary Color. Strict Good Ordinary Color is color which is within the range represented by a set of samples in the custody of the...

  13. 7 CFR 28.402 - Strict Middling Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Color. 28.402 Section 28.402... for the Color Grade of American Upland Cotton § 28.402 Strict Middling Color. Strict Middling Color is color which is within the range represented by a set of samples in the custody of the United States...

  14. Diversity and Antagonistic Activity of Actinomycete Strains From Myristica Swamp Soils Against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Varghese Rlnoy

    2014-05-01

    Full Text Available Under the present investigation Actinomycetes were isolated from the soils of Myristica swamps of southern Western Ghats and the antagonistic activity against different human bacterial pathogens was evaluated. Results of the present study revealed that Actinomycetes population in the soils of Myristica swamp was spatially and seasonally varied. Actinomycetes load was varied from 24×104 to 71×103, from 129×103 to 40×103 and from 31×104 to 84×103 in post monsoon, monsoon and pre monsoon respectively. A total of 23 Actinomycetes strains belonging to six genera were isolated from swamp soils. Identification of the isolates showed that most of the isolates belonged to the genus Streptomyces (11, followed by Nocardia (6, Micromonospora (3, Pseudonocardia (1, Streptosporangium (1, and Nocardiopsis (1. Antagonistic studies revealed that 91.3% of Actinomycete isolates were active against one or more tested pathogens, of that 56.52% exhibited activity against Gram negative and 86.95% showed activity against Gram positive bacteria. 39.13% isolates were active against all the bacterial pathogens selected and its inhibition zone diameter was also high. 69.5% of Actinomycetes were exhibited antibacterial activity against Listeria followed by Bacillus cereus (65.21%, Staphylococcus (60.86%, Vibrio cholera (52.17%, Salmonella (52.17% and E. coli (39.13%. The results indicate that the Myristica swamp soils of Southern Western Ghats might be a remarkable reserve of Actinomycetes with potential antagonistic activity.

  15. Transmission of Bacterial Zoonotic Pathogens between Pets and Humans: The Role of Pet Food.

    Science.gov (United States)

    Lambertini, Elisabetta; Buchanan, Robert L; Narrod, Clare; Pradhan, Abani K

    2016-01-01

    Recent Salmonella outbreaks associated with dry pet food and treats raised the level of concern for these products as vehicle of pathogen exposure for both pets and their owners. The need to characterize the microbiological and risk profiles of this class of products is currently not supported by sufficient specific data. This systematic review summarizes existing data on the main variables needed to support an ingredients-to-consumer quantitative risk model to (1) describe the microbial ecology of bacterial pathogens in the dry pet food production chain, (2) estimate pet exposure to pathogens through dry food consumption, and (3) assess human exposure and illness incidence due to contact with pet food and pets in the household. Risk models populated with the data here summarized will provide a tool to quantitatively address the emerging public health concerns associated with pet food and the effectiveness of mitigation measures. Results of such models can provide a basis for improvements in production processes, risk communication to consumers, and regulatory action.

  16. Antibacterial activity of different extracts of prawn shell (Macrobrachium nipponense against human bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Katayoon Karimzadeh

    2017-01-01

    Full Text Available Aims: Bioactive compounds existing in crustacean shells have the potential to inhibit the growth of some pathogenic microorganism. The purpose of this study is to evaluate the antibacterial effects of different extracts of prawn shells (Macrobrachium nipponense on some human pathogenic bacteria. Materials and Methods: Sampling (prawn was conducted in summer 2014 from Anzali wetland in southern coast of Caspian Sea. Then, the hydroalcoholic, methanolic, and acetone extracts of prawn shells were applied for this purpose. Two Gram-positive (Bacillus subtilis Staphylococcus aureus and three Gram-negative (Klebsiella pneumoniae, Vibrio cholerae, and Escherichia coli were used as test organisms. The antibacterial activity was determined by paper disk diffusion. Results: The prawn shell extracts showed activity against pathogenic bacteria. The highest antibacterial activities were measured in B. subtilis, S. aureus, and V. cholerae with the zone of inhibition being 12.12 ± 0.32 mm, 12.51 ± 0.14 mm, and 12.35 ± 0.27 mm, respectively. Among all the strains, S. aureus exhibits a significant zone of inhibition against all extracts (P < 0.05. Conclusion: The findings of this research showed that different prawn shell extracts, particularly hydroalcoholic, have bactericidal effect on B. subtilis, S. aureus, and V. cholerae species.

  17. CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells.

    Science.gov (United States)

    Ziegler, Sabrina; Weiss, Esther; Schmitt, Anna-Lena; Schlegel, Jan; Burgert, Anne; Terpitz, Ulrich; Sauer, Markus; Moretta, Lorenzo; Sivori, Simona; Leonhardt, Ines; Kurzai, Oliver; Einsele, Hermann; Loeffler, Juergen

    2017-07-21

    Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.

  18. Presence of potentially pathogenic Babesia sp. for human in Ixodes ricinus in Switzerland.

    Science.gov (United States)

    Casati, Simona; Sager, Heinz; Gern, Lise; Piffaretti, Jean-Claude

    2006-01-01

    We have designed and performed a new PCR method based on the 18S rRNA in order to individuate the presence and the identity of Babesia parasites. Out of 1159 Ixodes ricinus (Acari: Ixodidae) ticks collected in four areas of Switzerland, nine were found to contain Babesia DNA. Sequencing of the short amplicon obtained (411-452 bp) allowed the identification of three human pathogenic species: Babesia microti, B. divergens, for the first time in Switzerland, Babesia sp. EU1. We also report coinfections with B. sp. EU1-Borrelia burgdorferi sensu stricto and Babesia sp. EU1-B. afzelii.

  19. The Genome of the Basidiomycetous Yeast and Human Pathogen Cryptococcus neoformans

    Science.gov (United States)

    Loftus, Brendan J.; Fung, Eula; Roncaglia, Paola; Rowley, Don; Amedeo, Paolo; Bruno, Dan; Vamathevan, Jessica; Miranda, Molly; Anderson, Iain J.; Fraser, James A.; Allen, Jonathan E.; Bosdet, Ian E.; Brent, Michael R.; Chiu, Readman; Doering, Tamara L.; Donlin, Maureen J.; D’Souza, Cletus A.; Fox, Deborah S.; Grinberg, Viktoriya; Fu, Jianmin; Fukushima, Marilyn; Haas, Brian J.; Huang, James C.; Janbon, Guilhem; Jones, Steven J. M.; Koo, Hean L.; Krzywinski, Martin I.; Kwon-Chung, June K.; Lengeler, Klaus B.; Maiti, Rama; Marra, Marco A.; Marra, Robert E.; Mathewson, Carrie A.; Mitchell, Thomas G.; Pertea, Mihaela; Riggs, Florenta R.; Salzberg, Steven L.; Schein, Jacqueline E.; Shvartsbeyn, Alla; Shin, Heesun; Shumway, Martin; Specht, Charles A.; Suh, Bernard B.; Tenney, Aaron; Utterback, Terry R.; Wickes, Brian L.; Wortman, Jennifer R.; Wye, Natasja H.; Kronstad, James W.; Lodge, Jennifer K.; Heitman, Joseph; Davis, Ronald W.; Fraser, Claire M.; Hyman, Richard W.

    2012-01-01

    Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its ~20-megabase genome, which contains ~6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which cluster at candidate centromeric regions. The presence of these transposons may drive karyotype instability and phenotypic variation. C. neoformans encodes unique genes that may contribute to its unusual virulence properties, and comparison of two phenotypically distinct strains reveals variation in gene content in addition to sequence polymorphisms between the genomes. PMID:15653466

  20. More strictly protected areas are not necessarily more protective: evidence from Bolivia, Costa Rica, Indonesia, and Thailand

    International Nuclear Information System (INIS)

    Ferraro, Paul J; Hanauer, Merlin M; Miteva, Daniela A; Pattanayak, Subhrendu K; Canavire-Bacarreza, Gustavo Javier; Sims, Katharine R E

    2013-01-01

    National parks and other protected areas are at the forefront of global efforts to protect biodiversity and ecosystem services. However, not all protection is equal. Some areas are assigned strict legal protection that permits few extractive human uses. Other protected area designations permit a wider range of uses. Whether strictly protected areas are more effective in achieving environmental objectives is an empirical question: although strictly protected areas legally permit less anthropogenic disturbance, the social conflicts associated with assigning strict protection may lead politicians to assign strict protection to less-threatened areas and may lead citizens or enforcement agents to ignore the strict legal restrictions. We contrast the impacts of strictly and less strictly protected areas in four countries using IUCN designations to measure de jure strictness, data on deforestation to measure outcomes, and a quasi-experimental design to estimate impacts. On average, stricter protection reduced deforestation rates more than less strict protection, but the additional impact was not always large and sometimes arose because of where stricter protection was assigned rather than regulatory strictness per se. We also show that, in protected area studies contrasting y management regimes, there are y 2 policy-relevant impacts, rather than only y, as earlier studies have implied. (letter)

  1. Xenosurveillance: a novel mosquito-based approach for examining the human-pathogen landscape.

    Directory of Open Access Journals (Sweden)

    Nathan D Grubaugh

    2015-03-01

    Full Text Available Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations.To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host's blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus.Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts.

  2. Statistical approaches to developing a multiplex immunoassay for determining human exposure to environmental pathogens.

    Science.gov (United States)

    Augustine, Swinburne A J; Simmons, Kaneatra J; Eason, Tarsha N; Griffin, Shannon M; Curioso, Clarissa L; Wymer, Larry J; Shay Fout, G; Grimm, Ann C; Oshima, Kevin H; Dufour, Al

    2015-10-01

    There are numerous pathogens that can be transmitted through water. Identifying and understanding the routes and magnitude of exposure or infection to these microbial contaminants are critical to assessing and mitigating risk. Conventional approaches of studying immunological responses to exposure or infection such as Enzyme-Linked Immunosorbent Assays (ELISAs) and other monoplex antibody-based immunoassays can be very costly, laborious, and consume large quantities of patient sample. A major limitation of these approaches is that they can only be used to measure one analyte at a time. Multiplex immunoassays provide the ability to study multiple pathogens simultaneously in microliter volumes of samples. However, there are several challenges that must be addressed when developing these multiplex immunoassays such as selection of specific antigens and antibodies, cross-reactivity, calibration, protein-reagent interferences, and the need for rigorous optimization of protein concentrations. In this study, a Design of Experiments (DOE) approach was used to optimize reagent concentrations for coupling selected antigens to Luminex™ xMAP microspheres for use in an indirect capture, multiplex immunoassay to detect human exposure or infection from pathogens that are potentially transmitted through water. Results from Helicobacter pylori, Campylobacter jejuni, Escherichia coli O157:H7, and Salmonella typhimurium singleplexes were used to determine the mean concentrations that would be applied to the multiplex assay. Cut-offs to differentiate between exposed and non-exposed individuals were determined using finite mixed modeling (FMM). The statistical approaches developed facilitated the detection of Immunoglobulin G (IgG) antibodies to H. pylori, C. jejuni, Toxoplasma gondii, hepatitis A virus, rotavirus and noroviruses (VA387 and Norwalk strains) in fifty-four diagnostically characterized plasma samples. Of the characterized samples, the detection rate was 87.5% for H

  3. From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.

    Directory of Open Access Journals (Sweden)

    Geraldine Mulley

    Full Text Available Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called "nutritional virulence" strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.

  4. Mammalian evolution may not be strictly bifurcating.

    Science.gov (United States)

    Hallström, Björn M; Janke, Axel

    2010-12-01

    The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1-4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100-80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation.

  5. Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

    Science.gov (United States)

    In, Julie G; Foulke-Abel, Jennifer; Estes, Mary K; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark

    2016-11-01

    The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5 + intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

  6. Human mini-guts: new insights into intestinal physiology and host–pathogen interactions

    Science.gov (United States)

    In, Julie G.; Foulke-Abel, Jennifer; Estes, Mary K.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark

    2016-01-01

    The development of indefinitely propagating human ‘mini-guts’ has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt–villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host pathogen interactions. PMID:27677718

  7. Pathogen Loading From Canada Geese Faeces in Freshwater: Potential Risks to Human Health Through Recreational Water Exposure.

    Science.gov (United States)

    Gorham, T J; Lee, J

    2016-05-01

    Canada geese (Branta canadensis) faeces have been shown to contain pathogenic protozoa and bacteria in numerous studies over the past 15 years. Further, increases in both the Canada geese populations and their ideal habitat requirements in the United States (US) translate to a greater presence of these human pathogens in public areas, such as recreational freshwater beaches. Combining these factors, the potential health risk posed by Canada geese faeces at freshwater beaches presents an emerging public health issue that warrants further study. Here, literature concerning human pathogens in Canada geese faeces is reviewed and the potential impacts these pathogens may have on human health are discussed. Pathogens of potential concern include Campylobacter jejuni, Salmonella Typhimurium, Listeria monocytogenes, Helicobacter canadensis, Arcobacter spp., Enterohemorragic Escherichia coli pathogenic strains, Chlamydia psitacci, Cryptosporidium parvum and Giardia lamblia. Scenarios presenting potential exposure to pathogens eluted from faeces include bathers swimming in lakes, children playing with wet and dry sand impacted by geese droppings and other common recreational activities associated with public beaches. Recent recreational water-associated disease outbreaks in the US support the plausibility for some of these pathogens, including Cryptosporidium spp. and C. jejuni, to cause human illness in this setting. In view of these findings and the uncertainties associated with the real health risk posed by Canada geese faecal pathogens to users of freshwater lakes, it is recommended that beach managers use microbial source tracking and conduct a quantitative microbial risk assessment to analyse the local impact of Canada geese on microbial water quality during their decision-making process in beach and watershed management. © 2015 Blackwell Verlag GmbH.

  8. Antimicrobial Activity of Croton macrostachyus Stem Bark Extracts against Several Human Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Jackie K. Obey

    2016-01-01

    Full Text Available In Kenya, leaves and roots from Croton macrostachyus are used as a traditional medicine for infectious diseases such as typhoid and measles, but reports on possible antimicrobial activity of stem bark do not exist. In this study, the antibacterial and antifungal effects of methanol, ethyl acetate and butanol extracts, and purified lupeol of C. macrostachyus stem bark were determined against important human gram-negative pathogens Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, and Enterobacter aerogenes, gram-positive Listeria monocytogenes, and a fungus Candida albicans. The most promising broad scale antimicrobial activity against all the studied pathogens was shown by the ethyl acetate extract. The ethyl acetate extract induced the zone of inhibition between 10.1±0.6 mm and 16.0±1.2 mm against S. typhi, E. coli, K. pneumoniae, E. aerogenes, and L. monocytogenes with weaker antimicrobial activity against C. albicans (zone of inhibition: 5.6±1.0 mm. The antibiotic controls (amoxicillin, ciprofloxacin, ampicillin, benzylpenicillin, clotrimazole, and cefotaxime showed antimicrobial activity with zones of inhibition within 13.4±0.7–22.1±0.9 mm. The ethyl acetate extract had MIC in the range of 125–250 mg/mL against all the studied bacteria and against C. albicans MIC was 500 mg/mL. The present results give scientific evidence and support the traditional use of C. macrostachyus stem bark as a source for antimicrobials. We show that C. macrostachyus stem bark lupeol is a promising antimicrobial agent against several important human pathogens.

  9. Conidial Dihydroxynaphthalene Melanin of the Human Pathogenic Fungus Aspergillus fumigatus Interferes with the Host Endocytosis Pathway.

    Science.gov (United States)

    Thywißen, Andreas; Heinekamp, Thorsten; Dahse, Hans-Martin; Schmaler-Ripcke, Jeannette; Nietzsche, Sandor; Zipfel, Peter F; Brakhage, Axel A

    2011-01-01

    Aspergillus fumigatus is the most important air-borne fungal pathogen of humans. The interaction of the pathogen with the host's immune system represents a key process to understand pathogenicity. For elimination of invading microorganisms, they need to be efficiently phagocytosed and located in acidified phagolysosomes. However, as shown previously, A. fumigatus is able to manipulate the formation of functional phagolysosomes. Here, we demonstrate that in contrast to pigmentless pksP mutant conidia of A. fumigatus, the gray-green wild-type conidia inhibit the acidification of phagolysosomes of alveolar macrophages, monocyte-derived macrophages, and human neutrophil granulocytes. Therefore, this inhibition is independent of the cell type and applies to the major immune effector cells required for defense against A. fumigatus. Studies with melanin ghosts indicate that the inhibitory effect of wild-type conidia is due to their dihydroxynaphthalene (DHN)-melanin covering the conidia, whereas the hydrophobin RodA rodlet layer plays no role in this process. This is also supported by the observation that pksP conidia still exhibit the RodA hydrophobin layer, as shown by scanning electron microscopy. Mutants defective in different steps of the DHN-melanin biosynthesis showed stronger inhibition than pksP mutant conidia but lower inhibition than wild-type conidia. Moreover, A. fumigatus and A. flavus led to a stronger inhibition of phagolysosomal acidification than A. nidulans and A. terreus. These data indicate that a certain type of DHN-melanin that is different in the various Aspergillus species, is required for maximal inhibition of phagolysosomal acidification. Finally, we identified the vacuolar ATPase (vATPase) as potential target for A. fumigatus based on the finding that addition of bafilomycin which inhibits vATPase, led to complete inhibition of the acidification whereas the fusion of phagosomes containing wild-type conidia and lysosomes was not affected.

  10. A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus.

    Science.gov (United States)

    Shelburne, Samuel A; Keith, David; Horstmann, Nicola; Sumby, Paul; Davenport, Michael T; Graviss, Edward A; Brennan, Richard G; Musser, James M

    2008-02-05

    Although central to pathogenesis, the molecular mechanisms used by microbes to regulate virulence factor production in specific environments during host-pathogen interaction are poorly defined. Several recent ex vivo and in vivo studies have found that the level of group A Streptococcus (GAS) virulence factor gene transcripts is temporally related to altered expression of genes encoding carbohydrate utilization proteins. These findings stimulated us to analyze the role in pathogenesis of catabolite control protein A (CcpA), a GAS ortholog of a key global regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch as the genomewide effects of CcpA in a human pathogen are unknown, we analyzed the transcriptome of a DeltaccpA isogenic mutant strain grown in nutrient-rich medium. CcpA influences the transcript levels of many carbohydrate utilization genes and several well characterized GAS virulence factors, including the potent cytolysin streptolysin S. Compared with the wild-type parental strain, the DeltaccpA isogenic mutant strain was significantly less virulent in a mouse model of invasive infection. Moreover, the isogenic mutant strain was significantly impaired in ability to colonize the mouse oropharynx. When grown in human saliva, a nutrient-limited environment, CcpA influenced production of several key virulence factors not influenced during growth in nutrient-rich medium. Purified recombinant CcpA bound to the promoter region of the gene encoding streptolysin S. Our discovery that GAS virulence and complex carbohydrate utilization are directly linked through CcpA provides enhanced understanding of a mechanism used by a Gram-positive pathogen to modulate virulence factor production in specific environments.

  11. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Chandra L Shrestha

    Full Text Available Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF. We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS activation of transglutaminase-2 (TG2, which causes the sequestration (accumulation of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.

  12. Helicobacter pylori the Latent Human Pathogen or an Ancestral Commensal Organism

    Directory of Open Access Journals (Sweden)

    Jackie Li

    2018-04-01

    Full Text Available We dedicated this review to discuss Helicobacter pylori as one of the latest identified bacterial pathogens in humans and whether its role is mainly as a pathogen or a commensal. Diseases associated with this bacterium were highly prevalent during the 19th century and gradually have declined. Most diseases associated with H. pylori occurred in individuals older than 40 years of age. However, acquisition of H. pylori occurs mainly in young children inside the family setting. Prevalence and incidence of H. pylori has had a dramatic change in the last part of the 20th century and beginning of the 21th century. In developed countries there is a clear interruption of transmission and the lowest prevalence is observed in children younger than 10 years in these countries. A similar decline is observed but not at the same level in developing countries. Here we discuss the impact of the presence or absence of H. pylori in the health status of humans. We also discuss whether it is necessary or not to establish H. pylori eradication programs on light of the current decline in H. pylori prevalence.

  13. Application of bacteriophages in post-harvest control of human pathogenic and food spoiling bacteria.

    Science.gov (United States)

    Pérez Pulido, Rubén; Grande Burgos, Maria José; Gálvez, Antonio; Lucas López, Rosario

    2016-10-01

    Bacteriophages have attracted great attention for application in food biopreservation. Lytic bacteriophages specific for human pathogenic bacteria can be isolated from natural sources such as animal feces or industrial wastes where the target bacteria inhabit. Lytic bacteriophages have been tested in different food systems for inactivation of main food-borne pathogens including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, Salmonella enterica, Shigella spp., Campylobacter jejuni and Cronobacter sakazkii, and also for control of spoilage bacteria. Application of lytic bacteriophages could selectively control host populations of concern without interfering with the remaining food microbiota. Bacteriophages could also be applied for inactivation of bacteria attached to food contact surfaces or grown as biofilms. Bacteriophages may receive a generally recognized as safe status based on their lack of toxicity and other detrimental effects to human health. Phage preparations specific for L. monocytogenes, E. coli O157:H7 and S. enterica serotypes have been commercialized and approved for application in foods or as part of surface decontamination protocols. Phage endolysins have a broader host specificity compared to lytic bacteriophages. Cloned endolysins could be used as natural preservatives, singly or in combination with other antimicrobials such as bacteriocins.

  14. TLR-dependent human mucosal epithelial cell responses to microbial pathogens.

    Directory of Open Access Journals (Sweden)

    Paola eMassari

    2014-08-01

    Full Text Available AbstractToll-Like Receptor (TLR signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in humans as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites, specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners, their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

  15. Bactericidal activity of bio-synthesized silver nanoparticles against human pathogenic bacteria

    International Nuclear Information System (INIS)

    Abalkhil, Tarad Abdulaziz; Alharbi, Sulaiman Ali; Salmen, Saleh Hussein; Wainwright, Milton

    2017-01-01

    Green synthesis is an attractive and eco-friendly approach to generate potent antibacterial silver nanoparticles (Ag-NPs). Such particles have long been used to fight bacteria and represent a promising tool to overcome the emergence of antibiotic-resistant bacteria. In this study, green synthesis of Ag-NPs was attempted using plant extracts of Aloe vera, Portulaca oleracea and Cynodon dactylon. The identity and size of Ag-NPs was characterized by ultraviolet–visible spectrophotometer and scanning electron microscopy. Monodispersed Ag-NPs were produced with a range of different sizes based on the plant extract used. The bactericidal activity of Ag-NPs against a number of human pathogenic bacteria was determined using the disc diffusion method. The results showed that Gram positive bacteria were more susceptible than Gram negative ones to these antibacterial agents. The minimum inhibitory concentration was determined using the 96- well plate method. Finally, the mechanism by which Ag-NPs affect bacteria was investigated by SEM analysis. Bacteria treated with Ag-NPs were seen to undergo shrinkage and to lose their viability. This study provides evidence for a cheap and effective method for synthesizing potent bactericidal Ag-NPs and demonstrates their effectiveness against human pathogenic bacteria

  16. Gold Nanoparticles: An Efficient Antimicrobial Agent against Enteric Bacterial Human Pathogen

    Directory of Open Access Journals (Sweden)

    Shahzadi Shamaila

    2016-04-01

    Full Text Available Enteric bacterial human pathogens, i.e., Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Klebsiella pneumoniae, are the major cause of diarrheal infections in children and adults. Their structure badly affects the human immune system. It is important to explore new antibacterial agents instead of antibiotics for treatment. This project is an attempt to explain how gold nanoparticles affect these bacteria. We investigated the important role of the mean particle size, and the inhibition of a bacterium is dose-dependent. Ultra Violet (UV-visible spectroscopy revealed the size of chemically synthesized gold nanoparticle as 6–40 nm. Atomic force microscopy (AFM analysis confirmed the size and X-ray diffractometry (XRD analysis determined the polycrystalline nature of gold nanoparticles. The present findings explained how gold nanoparticles lyse Gram-negative and Gram-positive bacteria.

  17. Cationic amphipathic peptides, derived from bovine and human lactoferrins, with antimicrobial activity against oral pathogens.

    Science.gov (United States)

    Groenink, J; Walgreen-Weterings, E; van 't Hof, W; Veerman, E C; Nieuw Amerongen, A V

    1999-10-15

    Peptides derived from the N-terminal domain that comprises an amphipathic alpha-helix in human lactoferrin (LFh 18-31 and LFh 20-38) and bovine lactoferrin (LFb 17-30 and LFb 19-37) were chemically synthesised. Since many positively charged amphipathic alpha-helices contain antimicrobial activity, the peptides were tested for their antimicrobial activity against various oral pathogens. Both peptides from bovine lactoferrin had more potent antimicrobial activities than the human equivalents. Peptide LFb 17-30, containing the largest number of positively charged amino acids, showed the highest antimicrobial activity to both Gram-positive and Gram-negative bacteria. Since native lactoferrin molecules had no killing activity, release of these peptides from the native protein should be investigated to explore the use in oral care products.

  18. The complete genome sequence and analysis of the human pathogen Campylobacter lari

    DEFF Research Database (Denmark)

    Miller, WG; Wang, G; Binnewies, Tim Terence

    2008-01-01

    Campylobacter lari is a member of the epsilon subdivision of the Proteobacteria and is part of the thermotolerant Campylobacter group, a clade that includes the human pathogen C. jejuni. Here we present the complete genome sequence of the human clinical isolate, C. lari RM2100. The genome of strain...... RM2100 is approximately 1.53 Mb and includes the 46 kb megaplasmid pCL2100. Also present within the strain RM2100 genome is a 36 kb putative prophage, termed CLIE1, which is similar to CJIE4, a putative prophage present within the C. jejuni RM1221 genome. Nearly all (90%) of the gene content...... in strain RM2100 is similar to genes present in the genomes of other characterized thermotolerant campylobacters. However, several genes involved in amino acid biosynthesis and energy metabolism, identified previously in other Campylobacter genomes, are absent from the C. lari RM2100 genome. Therefore, C...

  19. Control of human pathogenic Yersinia enterocolitica in minced meat: Comparative analysis of different interventions using a risk assessment approach

    DEFF Research Database (Denmark)

    Van Damme, I.; De Zutter, L.; Jacxsens, L.

    2017-01-01

    This study aimed to evaluate the effect of different processing scenarios along the farm-to-fork chain on the contamination of minced pork with human pathogenic Y. enterocolitica. A modular process risk model (MPRM) was used to perform the assessment of the concentrations of pathogenic Y. enterocolitica...... in minced meat produced in industrial meat processing plants. The model described the production of minced pork starting from the contamination of pig carcasses with pathogenic Y. enterocolitica just before chilling. The endpoints of the assessment were (i) the proportion of 0.5 kg minced meat packages...... that contained pathogenic Y. enterocolitica and (ii) the proportion of 0.5 kg minced meat packages that contained more than 10³ pathogenic Y. enterocolitica at the end of storage, just before consumption of raw pork or preparation. Comparing alternative scenarios to the baseline model showed that the initial...

  20. Comparative genomics allowed the identification of drug targets against human fungal pathogens

    Directory of Open Access Journals (Sweden)

    Martins Natalia F

    2011-01-01

    Full Text Available Abstract Background The prevalence of invasive fungal infections (IFIs has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases. Results In silico analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for Candida albicans or Aspergillus fumigatus and other 2 genes (kre2 and erg6 relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (C. albicans, A. fumigatus, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Paracoccidioides lutzii, Coccidioides immitis, Cryptococcus neoformans and Histoplasma capsulatum. Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for α-1,2-mannosyltransferase and erg6 that encodes for Δ(24-sterol C-methyltransferase. Conclusions Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of

  1. Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii.

    Science.gov (United States)

    Müller, Gabriela L; Tuttobene, Marisel; Altilio, Matías; Martínez Amezaga, Maitena; Nguyen, Meaghan; Cribb, Pamela; Cybulski, Larisa E; Ramírez, María Soledad; Altabe, Silvia; Mussi, María Alejandra

    2017-05-15

    Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii , light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of the A. baumannii lifestyle. IMPORTANCE The discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogen Acinetobacter baumannii In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In

  2. Environmental controls, oceanography and population dynamics of pathogens and harmful algal blooms: connecting sources to human exposure

    Directory of Open Access Journals (Sweden)

    Minnett Peter

    2008-11-01

    Full Text Available Abstract Coupled physical-biological models are capable of linking the complex interactions between environmental factors and physical hydrodynamics to simulate the growth, toxicity and transport of infectious pathogens and harmful algal blooms (HABs. Such simulations can be used to assess and predict the impact of pathogens and HABs on human health. Given the widespread and increasing reliance of coastal communities on aquatic systems for drinking water, seafood and recreation, such predictions are critical for making informed resource management decisions. Here we identify three challenges to making this connection between pathogens/HABs and human health: predicting concentrations and toxicity; identifying the spatial and temporal scales of population and ecosystem interactions; and applying the understanding of population dynamics of pathogens/HABs to management strategies. We elaborate on the need to meet each of these challenges, describe how modeling approaches can be used and discuss strategies for moving forward in addressing these challenges.

  3. Comparative genomics of pathogenic Leptospira interrogans serovar Canicola isolated from swine and human in Brazil

    Directory of Open Access Journals (Sweden)

    Luisa Z Moreno

    Full Text Available Leptospira interrogans serovar Canicola is one of the most important pathogenic serovars for the maintenance of urban leptospirosis. Even though it is considered highly adapted to dogs, serovar Canicola infection has already been described in other animals and even a few human cases. Here, we present the genomic characterisation of two Brazilian L. interrogans serovar Canicola strains isolated from slaughtered sows (L0-3 and L0-4 and their comparison with human strain Fiocruz LV133. It was observed that the porcine serovar Canicola strains present the genetic machinery to cause human infection and, therefore, represent a higher risk to public health. Both human and porcine serovar Canicola isolates also presented sequences with high identity to the Chinese serovar Canicola published plasmids pGui1 and pGui2. The plasmids identification in the Brazilian and Chinese serovar Canicola strains suggest that extra-chromosomal elements are one more feature of this serovar that was previously unnoticed.

  4. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    DEFF Research Database (Denmark)

    Ali, Amjad; Naz, Anam; Soares, Siomar C.

    2015-01-01

    Helicobacter pylori is a human gastric pathogen implicated as the major cause of peptic ulcer and second leading cause of gastric cancer (similar to 70%) around the world. Conversely, an increased resistance to antibiotics and hindrances in the development of vaccines against H. pylori are observed......-genome approach; the predicted conserved gene families (1,193) constitute similar to 77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost...... homolog proteins were characterized as universal therapeutic targets against H. pylori based on their functional annotation and protein-protein interaction. Finally, pathogenomics and genome plasticity analysis revealed 3 highly conserved and 2 highly variable putative pathogenicity islands in all...

  5. Comparative study of erythromycin, amoxicillin and ampicillin antimicrobial activity against human respiratory tract pathogens.

    Science.gov (United States)

    Liss, R H; Norman, J C; Goldmann, D A

    1979-01-01

    An in vitro test system was used to compare the antimicrobial activity of erythromycin, amoxicillin and ampicillin against respiratory tract pathogens isolated from man. The minimum inhibitory concentrations (MICs) of fresh clinical isolates of Streptoccus pyogenes, Streptocuccus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to the macrolide and penicillins ranged between 0.01 and 0.9 microgram/ml. The microbes were exposed to each antibiotic for approximately 3 h at 1x,2x and 5x the relevant MIC. Irreversible surface defects and intracellular lesions were resolved by scanning and transmission electron microscopy in all antibiotic-treated bacterial species, irrespective of the antimicrobial used. In each case, inhibition of growth was recorded by turbometric assay; no significant difference was observed among the declining slopes of post-dosing growth curves for either erythromycin-, amoxicillin- or ampicillin-treated pathogens. The experimental observations show that the onset of antimicrobial activity and the bactericidal effectiveness of equipotent concentrations of erythromycin, amoxicillin and ampicillin were comparable in this study. The results complement previous clinical, bacteriologic and ultrastructure studies in vivo and demonstrate the contribution of the combined in vivo/in vitro study design for better understanding of antimicrobial activity in human respiratory tract infections.

  6. Genome Sequence Analysis of the Emerging Human Pathogenic Acetic Acid Bacterium Granulibacter bethesdensis▿ †

    Science.gov (United States)

    Greenberg, David E.; Porcella, Stephen F.; Zelazny, Adrian M.; Virtaneva, Kimmo; Sturdevant, Dan E.; Kupko, John J.; Barbian, Kent D.; Babar, Amenah; Dorward, David W.; Holland, Steven M.

    2007-01-01

    Chronic granulomatous disease (CGD) is an inherited immune deficiency characterized by increased susceptibility to infection with Staphylococcus, certain gram-negative bacteria, and fungi. Granulibacter bethesdensis, a newly described genus and species within the family Acetobacteraceae, was recently isolated from four CGD patients residing in geographically distinct locales who presented with fever and lymphadenitis. We sequenced the genome of the reference strain of Granulibacter bethesdensis, which was isolated from lymph nodes of the original patient. The genome contains 2,708,355 base pairs in a single circular chromosome, in which 2,437 putative open reading frames (ORFs) were identified, 1,470 of which share sequence similarity with ORFs in the nonpathogenic but related Gluconobacter oxydans genome. Included in the 967 ORFs that are unique to G. bethesdensis are ORFs potentially important for virulence, adherence, DNA uptake, and methanol utilization. GC% values and best BLAST analysis suggested that some of these unique ORFs were recently acquired. Comparison of G. bethesdensis to other known CGD pathogens demonstrated conservation of some putative virulence factors, suggesting possible common mechanisms involved in pathogenesis in CGD. Genotyping of the four patient isolates by use of a custom microarray demonstrated genome-wide variations in regions encoding DNA uptake systems and transcriptional regulators and in hypothetical ORFs. G. bethesdensis is a genetically diverse emerging human pathogen that may have recently acquired virulence factors new to this family of organisms. PMID:17827295

  7. Linalool-induced oxidative stress processes in the human pathogen Candida albicans.

    Science.gov (United States)

    Máté, Gábor; Kovács, Dominika; Gazdag, Zoltán; Pesti, Miklós; Szántó, Árpád

    2017-06-01

    The present study investigated the linalool (Lol)-induced effects in acute toxicity tests in the human pathogen Candida albicans (C. albicans). Lol treatments induced reduced germ tube formation of the pathogen, which plays a crucial role in the virulence. In comparison with the untreated control, the exposure of 107 cells ml -1 to 0.7 mM or 1.4 mM Lol for one hour induced 20% and 30% decrements, respectively, in the colony-forming ability. At the same time, these treatments caused dose-dependent decrease in the levels of superoxide anion radical and total reactive oxygen species, while there was 1.5 and 1.8-fold increases in the concentrations of peroxides and lipid peroxides, respectively, indicating oxidative stress induction in the presence of Lol. Lol treatments resulted in different adaptive modifications of the antioxidant system. In 0.7 mM-treated cells, decreased specific activities of superoxide dismutase and catalase were detected, while exposure to 1.4 mM Lol resulted in the up-regulation of catalase, glutathione reductase and glutathione peroxidases.

  8. An orphan chemotaxis sensor regulates virulence and antibiotic tolerance in the human pathogen Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Heather Pearl McLaughlin

    Full Text Available The synthesis of virulence factors by pathogenic bacteria is highly regulated and occurs in response to diverse environmental cues. An array of two component systems (TCSs serves to link perception of different cues to specific changes in gene expression and/or bacterial behaviour. Those TCSs that regulate functions associated with virulence represent attractive targets for interference in anti-infective strategies for disease control. We have previously identified PA2572 as a putative response regulator required for full virulence of Pseudomonas aeruginosa, the opportunistic human pathogen, to Galleria mellonella (Wax moth larvae. Here we have investigated the involvement of candidate sensors for signal transduction involving PA2572. Mutation of PA2573, encoding a probable methyl-accepting chemotaxis protein, gave rise to alterations in motility, virulence, and antibiotic resistance, functions which are also controlled by PA2572. Comparative transcriptome profiling of mutants revealed that PA2572 and PA2573 regulate expression of a common set of 49 genes that are involved in a range of biological functions including virulence and antibiotic resistance. Bacterial two-hybrid analysis indicated a REC-dependent interaction between PA2572 and PA2573 proteins. Finally expression of PA2572 in the PA2573 mutant background restored virulence to G. mellonella towards wild-type levels. The findings indicate a role for the orphan chemotaxis sensor PA2573 in the regulation of virulence and antibiotic tolerance in P. aeruginosa and indicate that these effects are exerted in part through signal transduction involving PA2572.

  9. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    Directory of Open Access Journals (Sweden)

    Marie Desnos-Ollivier

    Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

  10. Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori

    International Nuclear Information System (INIS)

    Han Cong; Wang Qi; Dong Lei; Sun Haifang; Peng Shuying; Chen Jing; Yang Yiming; Yue Jianmin; Shen Xu; Jiang Hualiang

    2004-01-01

    Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K cat of 3.4 s -1 , K m of 1.7 mM, and K cat /K m of 2000 M -1 s -1 . HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 deg. C. The enzyme activity of Co 2+ -containing HpPDF is apparently higher than that of Zn 2+ -containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori

  11. Molecular cloning and characterization of a new peptide deformylase from human pathogenic bacterium Helicobacter pylori.

    Science.gov (United States)

    Han, Cong; Wang, Qi; Dong, Lei; Sun, Haifang; Peng, Shuying; Chen, Jing; Yang, Yiming; Yue, Jianmin; Shen, Xu; Jiang, Hualiang

    2004-07-09

    Helicobacter pylori is a gram-negative pathogenic bacterium, which is associated with peptic ulcer disease and gastric cancer. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. In bacteria, peptide deformylase (PDF) catalyzes the removal of a formyl group from the N-termini of nascent polypeptides. Due to its essentiality and absence in mammalian cells, PDF has been considered as an attractive target for the discovery of novel antibiotics. In this work, a new PDF gene (def) from H. pylori strain SS1 was cloned, expressed, and purified in Escherichia coli system. Sequence alignment shows that H. pylori PDF (HpPDF) shares about 40% identity to E. coli PDF (EcPDF). The enzymatic properties of HpPDF demonstrate its relatively high activity toward formyl-Met-Ala-Ser, with K(cat) of 3.4s(-1), K(m) of 1.7 mM, and K(cat) / K(m) of 2000M(-1)s(-1). HpPDF enzyme appears to be fully active at pH between 8.0 and 9.0, and temperature 50 degrees C. The enzyme activity of Co(2+)-containing HpPDF is apparently higher than that of Zn(2+)-containing HpPDF. This present work thereby supplies a potential platform that facilitates the discovery of novel HpPDF inhibitors and further of possible antimicrobial agents against H. pylori.

  12. Gene expression platform for synthetic biology in the human pathogen Streptococcus pneumoniae.

    Science.gov (United States)

    Sorg, Robin A; Kuipers, Oscar P; Veening, Jan-Willem

    2015-03-20

    The human pathogen Streptococcus pneumoniae (pneumococcus) is a bacterium that owes its success to complex gene expression regulation patterns on both the cellular and the population level. Expression of virulence factors enables a mostly hazard-free presence of the commensal, in balance with the host and niche competitors. Under specific circumstances, changes in this expression can result in a more aggressive behavior and the reversion to the invasive form as pathogen. These triggering conditions are very difficult to study due to the fact that environmental cues are often unknown or barely possible to simulate outside the host (in vitro). An alternative way of investigating expression patterns is found in synthetic biology approaches of reconstructing regulatory networks that mimic an observed behavior with orthogonal components. Here, we created a genetic platform suitable for synthetic biology approaches in S. pneumoniae and characterized a set of standardized promoters and reporters. We show that our system allows for fast and easy cloning with the BglBrick system and that reliable and robust gene expression after integration into the S. pneumoniae genome is achieved. In addition, the cloning system was extended to allow for direct linker-based assembly of ribosome binding sites, peptide tags, and fusion proteins, and we called this new generally applicable standard "BglFusion". The gene expression platform and the methods described in this study pave the way for employing synthetic biology approaches in S. pneumoniae.

  13. Pathogen reduction by ultraviolet C light effectively inactivates human white blood cells in platelet products.

    Science.gov (United States)

    Pohler, Petra; Müller, Meike; Winkler, Carla; Schaudien, Dirk; Sewald, Katherina; Müller, Thomas H; Seltsam, Axel

    2015-02-01

    Residual white blood cells (WBCs) in cellular blood components induce a variety of adverse immune events, including nonhemolytic febrile transfusion reactions, alloimmunization to HLA antigens, and transfusion-associated graft-versus-host disease (TA-GVHD). Pathogen reduction (PR) methods such as the ultraviolet C (UVC) light-based THERAFLEX UV-Platelets system were developed to reduce the risk of transfusion-transmitted infection. As UVC light targets nucleic acids, it interferes with the replication of both pathogens and WBCs. This preclinical study aimed to evaluate the ability of UVC light to inactivate contaminating WBCs in platelet concentrates (PCs). The in vitro and in vivo function of WBCs from UVC-treated PCs was compared to that of WBCs from gamma-irradiated and untreated PCs by measuring cell viability, proliferation, cytokine secretion, antigen presentation in vitro, and xenogeneic GVHD responses in a humanized mouse model. UVC light was at least as effective as gamma irradiation in preventing GVHD in the mouse model. It was more effective in suppressing T-cell proliferation (>5-log reduction in the limiting dilution assay), cytokine secretion, and antigen presentation than gamma irradiation. The THERAFLEX UV-Platelets (MacoPharma) PR system can substitute gamma irradiation for TA-GVHD prophylaxis in platelet (PLT) transfusion. Moreover, UVC treatment achieves suppression of antigen presentation and inhibition of cytokine accumulation during storage of PCs, which has potential benefits for transfusion recipients. © 2014 AABB.

  14. Milk from transgenic goat expressing human lysozyme for recovery and treatment of gastrointestinal pathogens.

    Science.gov (United States)

    Carneiro, Igor de Sá; Menezes, José Nilson Rodrigues de; Maia, Julyana Almeida; Miranda, André Marrocos; Oliveira, Victor Bruno Soares de; Murray, James D; Maga, Elizabeth A; Bertolini, Marcelo; Bertolini, Luciana Relly

    2018-01-15

    Lysozyme is an important non-specific immune protein in human milk, modulating the immune response against bacterial infections. The aim of this study was to characterize the milk of a transgenic goat expressing a recombinant human lysozyme (rhLZ) in the milk, also testing the in vitro antibacterial activity of the rhLZ milk against pathogens of the gastrointestinal tract. Milk samples collected from Tg and non-transgenic goats (nTg) from the 3rd to the 11th week of lactation were submitted to physicochemical analyses, rhLZ semi-quantification, and to rhLZ antimicrobial activity against Micrococcus luteus, Shiguella sonnei and Enterococcus faecalis. Viability and cell migration were studied in ileum epithelial cells (IEC-18) in absence or presence of E. faecalis, Staphylococcus aureus, Escherichia coli (EPEC) and S. sonnei. The expression of ZO-1 and IL-6 genes was evaluated in IEC-18 to evaluate the effect of rhLZ milk on intestinal barrier function and intestinal inflammation. Physicochemical parameters between goat Tg and nTg milk were similar and within normal values for human consumption, with hLZ concentrations being similar between Tg (224μg/mL) and human (226μg/mL) milk. The Tg milk had bactericidal activity against M. luteus, no bactericidal effect on S. sonnei, and relative to discrete sensitivity against E. feacalis than controls. Better migrating parameters were observed in cells in culture with nTg and Tg than controls. In the presence of pathogens, the Tg milk promoted improved migrating parameters than controls, except for S. sonnei, with lower cell numbers in the presence of nTg samples and E. faecalis and S. sonnei. No differences in ZO-1 relative expression patterns were observed in cultured cells, with increased expression in IL-6 in cells exposed to nTg milk than controls, with the Tg group being similar to all groups. In conclusion, goat milk containing rhLZ demonstrated valid evidence for its potential use as a nutraceutical for improvement

  15. Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans

    Science.gov (United States)

    Douglas, Lois M.; Konopka, James. B.

    2017-01-01

    Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans. PMID:26920878

  16. Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans.

    Science.gov (United States)

    Luo, Shanshan; Skerka, Christine; Kurzai, Oliver; Zipfel, Peter F

    2013-12-15

    Candida albicans is a medically important fungus that can cause a wide range of diseases ranging from superficial infections to disseminated disease, which manifests primarily in immuno-compromised individuals. Despite the currently applied anti-fungal therapies, both mortality and morbidity caused by this human pathogenic fungus are still unacceptably high. Therefore new prophylactic and therapeutic strategies are urgently needed to prevent fungal infection. In order to define new targets for combating fungal disease, there is a need to understand the immune evasion strategies of C. albicans in detail. In this review, we summarize different sophisticated immune evasion strategies that are utilized by C. albicans. The description of the molecular mechanisms used for immune evasion does on one hand help to understand the infection process, and on the other hand provides valuable information to define new strategies and diagnostic approaches to fight and interfere with Candida infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Predicting the Pathogenic Impact of Sequence Variation in the Human Genome.

    Science.gov (United States)

    Rogers, Mark F; Shihab, Hashem A; Ferlaino, Michael; Gaunt, Tom R; Campbell, Colin

    2017-01-01

    Sequencing data will become widely available in clinical practice within the near future. Uptake of sequence data is currently being stimulated within the UK through the government-funded 100,000 genomes project (Genomics England), with many similar initiatives being planned and supported internationally. The analysis of the large volumes of data derived from sequencing programmes poses a major challenge for data analysis. In this paper we outline progress we have made in the development of predictors for estimating the pathogenic impact of single nucleotide variants, indels and haploinsufficiency in the human genome. The accuracy of these methods is enhanced through the development of disease-specific predictors, trained on appropriate data, and used within a specific disease context. We outline current research on the development of disease-specific predictors, specifically in the context of cancer research.

  18. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae

    DEFF Research Database (Denmark)

    Jamal, Syed Babar; Hassan, Syed Shah; Tiwari, Sandeep

    2017-01-01

    Corynebacterium diphtheriae (Cd) is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However...... of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23...... (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives). The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae...

  19. Pharmaceutical Properties of Marine Macroalgal Communities from Gulf of Mannar against Human Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    R. Lavanya

    2012-05-01

    Full Text Available Objective: To evaluate the antifungal activity of seaweed extracts against human fungal pathogens. Methods: Antifungal activity of six species of marine macro algae Codium decorticatum, Caulerpa scalpelliformis, Gracilaria crassa, Acanthophora spicifera, Sargassum wightii and Turbinaria conoides using different solvents acetone, methanol, chloroform, diethyl ether, ethyl acetate, hexane and aqueous were evaluated against Fusarium oxysporum, Fusarium udum, Fusarium solani, Rhizoctonia solani, Alternaria alternat, Botrytis cinerea, Candida albicans, Candida krusei, Aspergillus niger and Aspergillus flavus. Results: From the investigation, the maximum activity was recorded from Phaeophyceae, Chlorophyceae and Rhodophyceae respectively. The maximum inhibition zone was noted in acetone extract of T. conoides against F. udum. Conclusions: From these findings, it is concluded that brown seaweed Turbinaria conoides is more effective than the green and red seaweeds.

  20. The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens

    Directory of Open Access Journals (Sweden)

    Yong Mao

    2018-01-01

    Full Text Available Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.

  1. Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy.

    Science.gov (United States)

    Santos, L O; Garcia-Gomes, A S; Catanho, M; Sodre, C L; Santos, A L S; Branquinha, M H; d'Avila-Levy, C M

    2013-01-01

    Aspartic peptidases are proteolytic enzymes present in many organisms like vertebrates, plants, fungi, protozoa and in some retroviruses such as human immunodeficiency virus (HIV). These enzymes are involved in important metabolic processes in microorganisms/virus and play major roles in infectious diseases. Although few studies have been performed in order to identify and characterize aspartic peptidase in trypanosomatids, which include the etiologic agents of leishmaniasis, Chagas' disease and sleeping sickness, some beneficial properties of aspartic peptidase inhibitors have been described on fundamental biological events of these pathogenic agents. In this context, aspartic peptidase inhibitors (PIs) used in the current chemotherapy against HIV (e.g., amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) were able to inhibit the aspartic peptidase activity produced by different species of Leishmania. Moreover, the treatment of Leishmania promastigotes with HIV PIs induced several perturbations on the parasite homeostasis, including loss of the motility and arrest of proliferation/growth. The HIV PIs also induced an increase in the level of reactive oxygen species and the appearance of irreversible morphological alterations, triggering parasite death pathways such as programed cell death (apoptosis) and uncontrolled autophagy. The blockage of physiological parasite events as well as the induction of death pathways culminated in its incapacity to adhere, survive and escape of phagocytic cells. Collectively, these results support the data showing that parasites treated with HIV PIs have a significant reduction in the ability to cause in vivo infection. Similarly, the treatment of Trypanosoma cruzi cells with pepstatin A showed a significant inhibition on both aspartic peptidase activity and growth as well as promoted several and irreversible morphological changes. These studies indicate that aspartic peptidases can be promising targets in

  2. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

    Directory of Open Access Journals (Sweden)

    Syed Babar Jamal

    Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

  3. Antibacterial activities of Rhazya stricta leaf extracts against multidrug-resistant human pathogens

    Directory of Open Access Journals (Sweden)

    Raziuddin Khan

    2016-09-01

    Full Text Available Bacterial resistance to antibiotics, first a major concern in the 1960s, has re-emerged worldwide over the last 20 years. The World Health Organization (WHO and other health organizations have, therefore, declared ‘war’ against human microbial pathogens, particularly hospital-acquired infections, and have made drug discovery a top priority for these diseases. Because these bacteria are refractory to conventional chemotherapy, medicinal and herbal plants used in various countries should be assessed for their therapeutic potential; these valuable bio-resources are a reservoir of complex bioactive molecules. Earlier studies from our laboratory on Rhazya stricta, a native herbal shrub of Asia, have shown that this plant has a number of therapeutic properties. In this study, we evaluated the antimicrobial activities of various concentrations of five solvent extracts (aqueous alkaloid, aqueous non-alkaloid, organic alkaloid, organic non-alkaloid and whole aqueous extracts derived from R. stricta leaves against several multidrug-resistant, human-pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA and extended-spectrum beta-lactamase-positive Escherichia coli. In vitro, molecular and electron microscopy analyses conclusively demonstrated the antimicrobial effects of these extracts against a panel of Gram-negative and Gram-positive bacteria. The organic alkaloid extract was the most effective against E. coli and MRSA, resulting in cell membrane disruption visible with transmission electron microscopy. In the near future, we intend to further focus and delineate the molecular mechanism-of-action for specific alkaloids of R. stricta, particularly against MRSA.

  4. Bactericidal Effect of Gold-Chitosan Nanocomposites in Coculture Models of Pathogenic Bacteria and Human Macrophages.

    Science.gov (United States)

    Mendoza, Gracia; Regiel-Futyra, Anna; Andreu, Vanesa; Sebastián, Víctor; Kyzioł, Agnieszka; Stochel, Grażyna; Arruebo, Manuel

    2017-05-31

    The ability of pathogenic bacteria to develop resistance mechanisms to avoid the antimicrobial potential of antibiotics has become an increasing problem for the healthcare system. The search for more effective and selective antimicrobial materials, though not harmful to mammalian cells, seems imperative. Herein we propose the use of gold-chitosan nanocomposites as effective bactericidal materials avoiding damage to human cells. Nanocomposites were obtained by taking advantage of the reductive and stabilizing action of chitosan solutions on two different gold precursor concentrations. The resulting nanocomposites were added at different final concentrations to a coculture model formed by Gram-positive (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria and human macrophages. Gold-chitosan colloids exhibited superior bactericidal ability against both bacterial models without showing cytotoxicity on human cells at the concentrations tested. Morphological and in vitro viability studies supported the feasibility of the infection model here described to test novel bactericidal nanomaterials. Flow cytometry and scanning electron microscopy analyses pointed to the disruption of the bacterial wall as the lethal mechanism. Data obtained in the present study suggest that gold-chitosan nanocomposites are powerful and promising nanomaterials for reducing bacteria-associated infections, respecting the integrity of mammalian cells, and displaying high selectivity against the studied bacteria.

  5. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes

    KAUST Repository

    Moon, Robert

    2012-12-24

    Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.

  6. Antimicrobial Compounds from Eukaryotic Microalgae against Human Pathogens and Diseases in Aquaculture.

    Science.gov (United States)

    Falaise, Charlotte; François, Cyrille; Travers, Marie-Agnès; Morga, Benjamin; Haure, Joël; Tremblay, Réjean; Turcotte, François; Pasetto, Pamela; Gastineau, Romain; Hardivillier, Yann; Leignel, Vincent; Mouget, Jean-Luc

    2016-09-02

    The search for novel compounds of marine origin has increased in the last decades for their application in various areas such as pharmaceutical, human or animal nutrition, cosmetics or bioenergy. In this context of blue technology development, microalgae are of particular interest due to their immense biodiversity and their relatively simple growth needs. In this review, we discuss about the promising use of microalgae and microalgal compounds as sources of natural antibiotics against human pathogens but also about their potential to limit microbial infections in aquaculture. An alternative to conventional antibiotics is needed as the microbial resistance to these drugs is increasing in humans and animals. Furthermore, using natural antibiotics for livestock could meet the consumer demand to avoid chemicals in food, would support a sustainable aquaculture and present the advantage of being environmentally friendly. Using natural and renewable microalgal compounds is still in its early days, but considering the important research development and rapid improvement in culture, extraction and purification processes, the valorization of microalgae will surely extend in the future.

  7. Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms.

    Science.gov (United States)

    Laukkanen, Riikka; Martínez, Pilar Ortiz; Siekkinen, Kirsi-Maarit; Ranta, Jukka; Maijala, Riitta; Korkeala, Hannu

    2009-01-01

    Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.

  8. Comparison of the antimicrobial effects of semipurified cyclotides from Iranian Viola odorata against some of plant and human pathogenic bacteria.

    Science.gov (United States)

    Zarrabi, M; Dalirfardouei, R; Sepehrizade, Z; Kermanshahi, R K

    2013-08-01

    Cyclotides are mini-proteins that are synthesized via the ribosomal pathway. They have a variety of biological activities such as antimicrobial, antitumour, anti-HIV activities. Because of their various bioactivities and unique stability, they are suitable candidate in drug design applications. The main aim of this study was to determine new antimicrobial agents, which can be used instead of chemical antibiotics. For this reason, we compared the antimicrobial effects of semipurified cyclotides against human and plant pathogenic bacteria. The cyclotides were isolated from the Iranian plant Viola odorata by fractionation methods and semipurified on a SPE-C18 column chromatography. Antimicrobial activities of extracted cyclotides were studied by radial diffusion assays (RDAs), minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Data analysis showed that MIC of semipurified cyclotides was 1.6 mg ml(-1) against Staphylococcus aureus, gram-positive bacteria. It was also revealed they are the most susceptible among human pathogenic bacteria used in this research. On the other hand, plant pathogenic bacteria are more susceptible than human pathogenic bacteria. The results of the study show that cyclotides from Iranian V. odorata have potent antimicrobial activity against gram-negative, plant pathogenic bacteria. This study is a part of our extended researches on finding new pharmaceutical potentials of plants and on developing new peptides for special purposes in a way that does not have harmful side effects or have the least side effects. © 2013 The Society for Applied Microbiology.

  9. Modal Inclusion Logic: Being Lax is Simpler than Being Strict

    DEFF Research Database (Denmark)

    Hella, Lauri; Kuusisto, Antti Johannes; Meier, Arne

    2015-01-01

    We investigate the computational complexity of the satisfiability problem of modal inclusion logic. We distinguish two variants of the problem: one for strict and another one for lax semantics. The complexity of the lax version turns out to be complete for EXPTIME, whereas with strict semantics...

  10. 7 CFR 28.431 - Strict Middling Tinged Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Tinged Color. 28.431 Section 28.431 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Color. Strict Middling Tinged Color is color which is better than Middling Tinged Color. ...

  11. 7 CFR 28.433 - Strict Low Middling Tinged Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Tinged Color. 28.433 Section 28.433 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Tinged Color. Strict Low Middling Tinged Color is color which is within the range represented by a set of...

  12. 7 CFR 28.424 - Strict Low Middling Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Spotted Color. 28.424 Section 28.424 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Spotted Color. Strict Low Middling Spotted Color is color which is within the range represented by a set...

  13. 7 CFR 28.426 - Strict Good Ordinary Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Good Ordinary Spotted Color. 28.426 Section 28.426 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Spotted Color. Strict Good Ordinary Spotted Color is color which is within the range represented by a set...

  14. 7 CFR 28.422 - Strict Middling Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Spotted Color. 28.422 Section 28.422 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Color. Strict Middling Spotted Color is color which is within the range represented by a set of samples...

  15. Strictly-regular number system and data structures

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Jensen, Claus; Katajainen, Jyrki

    2010-01-01

    We introduce a new number system that we call the strictly-regular system, which efficiently supports the operations: digit-increment, digit-decrement, cut, concatenate, and add. Compared to other number systems, the strictly-regular system has distinguishable properties. It is superior to the re...

  16. Modulation of Stat-1 in Human Macrophages Infected with Different Species of Intracellular Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Giuditta Fiorella Schiavano

    2016-01-01

    Full Text Available The infection of human macrophages by pathogenic bacteria induces different signaling pathways depending on the type of cellular receptors involved in the microorganism entry and on their mechanism(s of survival and replication in the host cell. It was reported that Stat proteins play an important role in this process. In the present study, we investigate the changes in Stat-1 activation (phosphorylation in p-tyr701 after uptake of two Gram-positive (Listeria monocytogenes and Staphylococcus aureus and two Gram-negative bacteria (Salmonella typhimurium and Legionella pneumophila characterized by their varying abilities to enter, survive, and replicate in human macrophages. Comparing the results obtained with Gram-negative and Gram-positive bacteria, Stat-1 activation in macrophages does not seem to be related to LPS content. The p-tyr701Stat-1 expression levels were found to be independent of the internalized bacterial number and IFN-γ release. On the contrary, Jak/Stat-1 pathway activation only occurs when an active infection has been established in the host macrophage, and it is plausible that the differences in the expression levels of p-tyr701Stat-1 could be due to different survival mechanisms or to differences in bacteria life cycles within macrophages.

  17. Characterizing ncRNAs in human pathogenic protists using high-throughput sequencing technology

    Directory of Open Access Journals (Sweden)

    Lesley Joan Collins

    2011-12-01

    Full Text Available ncRNAs are key genes in many human diseases including cancer and viral infection, as well as providing critical functions in pathogenic organisms such as fungi, bacteria, viruses and protists. Until now the identification and characterization of ncRNAs associated with disease has been slow or inaccurate requiring many years of testing to understand complicated RNA and protein gene relationships. High-throughput sequencing now offers the opportunity to characterize miRNAs, siRNAs, snoRNAs and long ncRNAs on a genomic scale making it faster and easier to clarify how these ncRNAs contribute to the disease state. However, this technology is still relatively new, and ncRNA discovery is not an application of high priority for streamlined bioinformatics. Here we summarize background concepts and practical approaches for ncRNA analysis using high-throughput sequencing, and how it relates to understanding human disease. As a case study, we focus on the parasitic protists Giardia lamblia and Trichomonas vaginalis, where large evolutionary distance has meant difficulties in comparing ncRNAs with those from model eukaryotes. A combination of biological, computational and sequencing approaches has enabled easier classification of ncRNA classes such as snoRNAs, but has also aided the identification of novel classes. It is hoped that a higher level of understanding of ncRNA expression and interaction may aid in the development of less harsh treatment for protist-based diseases.

  18. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites.

    Science.gov (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon

    2008-12-01

    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  19. Filamentous Fungal Human Pathogens from Food Emphasising Aspergillus, Fusarium and Mucor.

    Science.gov (United States)

    Paterson, R Russell M; Lima, Nelson

    2017-08-02

    Disease caused by filamentous fungal human pathogens (FFHP) is increasing. These organisms cause severe mycoses in immunosuppressed individuals, such as those: (a) with AIDS; (b) having undergone transplantation; and/or (c) undergoing chemotherapy. Immunocompetent people can become infected. Some FFHP are isolated from foods which may be fomites. However, the information concerning particular species on specific food is large, dispersed and difficult to obtain. Reports of filamentous fungi from food/crops and causing human disease are frequently only available in the literature of food mycology/plant pathology and medical mycology, respectively: it is seldom cross-referenced. Aspergillus contains some species with strains that are the most dangerous FFHP, with Aspergillus fumigatus causing the most serious diseases. Fusarium and Mucor also contain species of high importance and approximately 15 other genera are involved. A checklist and database of FFHP species isolated from food is presented herein with emphasis on Aspergillus , Fusarium and Mucor in summary tables to increase awareness of the connection between food and FFHP. Metadata on all FFHP is provided in a large supplementary table for updating and revision when necessary. Previous names of fungi have been revised to reflect current valid usage whenever appropriate. The information will form a foundation for future research and taxonomic revisions in the field. The paper will be highly useful for medical practitioners, food mycologists, fungal taxonomists, patients, regulators and food producers interested in reducing infectious diseases and producing high quality food.

  20. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    International Nuclear Information System (INIS)

    Lemaire, D.; Barbosa, T.; Rihet, P.

    2011-01-01

    Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data

  1. The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review).

    Science.gov (United States)

    McLennan, A G

    1999-07-01

    Human cells express at least eight members of the MutT motif protein (or nudix hydrolase) family. These enzymes are believed to eliminate toxic nucleotide derivatives from the cell and regulate the levels of important signalling nucleotides and their metabolites. Six have been fully or partially characterized: i) hMTH1 is a nucleoside triphosphatase which restricts AT-->CG transversions by specifically degrading the oxidized nucleotide 8-oxo-dGTP; ii) hAPAH1 preferentially degrades the signalling dinucleotide Ap4A; iii) DIPP is unusual in hydrolysing two seemingly unrelated signalling substrate groups - the dinucleotides Ap6A and Ap5A, and the diphosphoinositol polyphosphates; iv) DIPP2 is closely related to DIPP; v) hYSAH1 is an NDP-sugar hydrolase which prefers ADP-ribose, and vi) hGFG is a protein of unknown function encoded by the antisense transcript of the basic fibroblast growth factor gene. Although not yet associated with known hereditary or acquired disorders, the functional loss of any one of these hydrolases would be expected to be detrimental to cellular function. Furthermore, the ialA invasion gene of Bartonella bacilliformis and other invasive pathogens encodes a MutT motif Ap4A hydrolase while poxviruses express two MutT motif proteins, at least one of which is essential for infectivity. This protein family, therefore, occupies a position of some importance in controlling human health and disease.

  2. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, D. [Universidade Federal da Bahia and Universidade Estadual da Bahia, Salvador, BA (Brazil); Barbosa, T. [Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA (Brazil); Rihet, P. [TAGC-INSERM U928, Aix-Marseille Université, Marseille (France)

    2011-10-28

    Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

  3. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Directory of Open Access Journals (Sweden)

    José F Muñoz

    2015-10-01

    Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics

  4. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Science.gov (United States)

    Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A

    2015-10-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution

  5. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

    Science.gov (United States)

    2012-01-01

    Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W) gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of this newly recognized

  6. Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient

    Directory of Open Access Journals (Sweden)

    Schröder Jasmin

    2012-04-01

    Full Text Available Abstract Background Corynebacterium resistens was initially recovered from human infections and recognized as a new coryneform species that is highly resistant to antimicrobial agents. Bacteremia associated with this organism in immunocompromised patients was rapidly fatal as standard minocycline therapies failed. C. resistens DSM 45100 was isolated from a blood culture of samples taken from a patient with acute myelocytic leukemia. The complete genome sequence of C. resistens DSM 45100 was determined by pyrosequencing to identify genes contributing to multi-drug resistance, virulence, and the lipophilic lifestyle of this newly described human pathogen. Results The genome of C. resistens DSM 45100 consists of a circular chromosome of 2,601,311 bp in size and the 28,312-bp plasmid pJA144188. Metabolic analysis showed that the genome of C. resistens DSM 45100 lacks genes for typical sugar uptake systems, anaplerotic functions, and a fatty acid synthase, explaining the strict lipophilic lifestyle of this species. The genome encodes a broad spectrum of enzymes ensuring the availability of exogenous fatty acids for growth, including predicted virulence factors that probably contribute to fatty acid metabolism by damaging host tissue. C. resistens DSM 45100 is able to use external L-histidine as a combined carbon and nitrogen source, presumably as a result of adaptation to the hitherto unknown habitat on the human skin. Plasmid pJA144188 harbors several genes contributing to antibiotic resistance of C. resistens DSM 45100, including a tetracycline resistance region of the Tet W type known from Lactobacillus reuteri and Streptococcus suis. The tet(W gene of pJA144188 was cloned in Corynebacterium glutamicum and was shown to confer high levels of resistance to tetracycline, doxycycline, and minocycline in vitro. Conclusions The detected gene repertoire of C. resistens DSM 45100 provides insights into the lipophilic lifestyle and virulence functions of

  7. Extension of Shelf Life and Control of Human Pathogens in Produce by Antimicrobial Edible Films and Coatings

    Science.gov (United States)

    This chapter provides general information about edible films and coatings, and their use with fruits and vegetables to control human pathogens. It reviews potential antimicrobial phytochemicals used in edible films and coatings, and summarizes methods for measuring the antimicrobial activity and ph...

  8. Risk-analysis of human pathogen spread in the vegetable industry: a comparison between organic and conventional production chains

    NARCIS (Netherlands)

    Franz, E.; Bruggen, van A.H.C.; Semenov, A.M.

    2004-01-01

    An overview is given of recent problems with food-borne enteric human pathogens originating from contaminated agricultural animals. The need for risk analysis is indicated, and the generally accepted procedure for risk assessment is outlined. Two main approaches to probability and risk calculations,

  9. Rapid identification of emerging human-pathogenic Sporothrix species with rolling circle amplification

    Directory of Open Access Journals (Sweden)

    Anderson Messias Rodrigues

    2015-12-01

    Full Text Available Sporothrix infections are emerging as an important human and animal threat among otherwise healthy patients, especially in Brazil and China. Correct identification of sporotrichosis agents is beneficial for epidemiological surveillance, enabling implementation of adequate public-health policies and guiding antifungal therapy. In areas of limited resources where sporotrichosis is endemic, high-throughput detection methods that are specific and sensitive are preferred over phenotypic methods that usually result in misidentification of closely related Sporothrix species. We sought to establish rolling circle amplification (RCA as a low-cost screening tool for species-specific identification of human-pathogenic Sporothrix. We developed six species-specific padlock probes targeting polymorphisms in the gene encoding calmodulin. BLAST-searches revealed candidate probes that were conserved intraspecifically; no significant homology with sequences from humans, mice, plants or microorganisms outside members of Sporothrix were found. The accuracy of our RCA-based assay was demonstrated through the specificity of probe-template binding to 25 S. brasiliensis, 58 S. schenckii, 5 S. globosa, 1 S. luriei, 4 S. mexicana, and 3 S. pallida samples. No cross reactivity between closely related species was evident in vitro, and padlock probes yielded 100% specificity and sensitivity down to 3 x 10 6 copies of the target sequence. RCA-based speciation matched identifications via phylogenetic analysis of the gene encoding calmodulin and the rDNA operon (kappa 1.0; 95% confidence interval 1.0-1.0, supporting its use as a reliable alternative to DNA sequencing. This method is a powerful tool for rapid identification and specific detection of medically relevant Sporothrix, and due to its robustness has potential for ecological studies.

  10. Rapid Identification of Emerging Human-Pathogenic Sporothrix Species with Rolling Circle Amplification

    Science.gov (United States)

    Rodrigues, Anderson M.; Najafzadeh, Mohammad J.; de Hoog, G. Sybren; de Camargo, Zoilo P.

    2015-01-01

    Sporothrix infections are emerging as an important human and animal threat among otherwise healthy patients, especially in Brazil and China. Correct identification of sporotrichosis agents is beneficial for epidemiological surveillance, enabling implementation of adequate public-health policies and guiding antifungal therapy. In areas of limited resources where sporotrichosis is endemic, high-throughput detection methods that are specific and sensitive are preferred over phenotypic methods that usually result in misidentification of closely related Sporothrix species. We sought to establish rolling circle amplification (RCA) as a low-cost screening tool for species-specific identification of human-pathogenic Sporothrix. We developed six species-specific padlock probes targeting polymorphisms in the gene encoding calmodulin. BLAST-searches revealed candidate probes that were conserved intraspecifically; no significant homology with sequences from humans, mice, plants or microorganisms outside members of Sporothrix were found. The accuracy of our RCA-based assay was demonstrated through the specificity of probe-template binding to 25 S. brasiliensis, 58 S. schenckii, 5 S. globosa, 1 S. luriei, 4 S. mexicana, and 3 S. pallida samples. No cross reactivity between closely related species was evident in vitro, and padlock probes yielded 100% specificity and sensitivity down to 3 × 106 copies of the target sequence. RCA-based speciation matched identifications via phylogenetic analysis of the gene encoding calmodulin and the rDNA operon (kappa 1.0; 95% confidence interval 1.0-1.0), supporting its use as a reliable alternative to DNA sequencing. This method is a powerful tool for rapid identification and specific detection of medically relevant Sporothrix, and due to its robustness has potential for ecological studies. PMID:26696992

  11. Fusarium musae, is also an opportunistic human pathogen: are bananas potential carriers and source of fusariosis? Mycologia

    OpenAIRE

    Triest, David; Pi?rard, Denis; De Cremer, Koen; Hendrickx, Marijke

    2016-01-01

    ABSTRACT The banana fruit infecting fungus Fusarium musae was originally known as a distinct population within Fusarium verticillioides. However, recently, Fusarium musae was installed as a separate species and the first cases of human infection associated with Fusarium musae were found. In this article, we report an additional survey indicating that human pathogenic Fusarium musae infections may occur more frequently than we might think. Moreover, we evaluate the hypotheses on how infection ...

  12. Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages.

    Directory of Open Access Journals (Sweden)

    Ludovic Tailleux

    2008-01-01

    Full Text Available Transcriptional profiling using microarrays provides a unique opportunity to decipher host pathogen cross-talk on the global level. Here, for the first time, we have been able to investigate gene expression changes in both Mycobacterium tuberculosis, a major human pathogen, and its human host cells, macrophages and dendritic cells.In addition to common responses, we could identify eukaryotic and microbial transcriptional signatures that are specific to the cell type involved in the infection process. In particular M. tuberculosis shows a marked stress response when inside dendritic cells, which is in accordance with the low permissivity of these specialized phagocytes to the tubercle bacillus and to other pathogens. In contrast, the mycobacterial transcriptome inside macrophages reflects that of replicating bacteria. On the host cell side, differential responses to infection in macrophages and dendritic cells were identified in genes involved in oxidative stress, intracellular vesicle trafficking and phagosome acidification.This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments.

  13. [A case of human highly pathogenic avian influenza in Shenzhen, China: application of field epidemiological study].

    Science.gov (United States)

    Zhang, Shun-Xiang; Cheng, Jin-Quan; Ma, Han-Wu; He, Jian-Fan; Cheng, Xiao-Wen; Jiang, Li-Juan; Mou, Jin; Wu, Chun-Li; Lv, Xing; Zhang, Shao-Hua; Zhang, Ya-De; Wu, Yong-Sheng; Wang, Xin

    2008-03-01

    Based on analyzing the characteristics of a case with human avian influenza and the effects of field epidemiological study. An emergency-response-system was started up to follow the probable human Highly Pathogenic Avian Influenza case initially detected by the "Undefined Pneumonia Surveillance System of Shenzhen". Public health professionals administered several epidemiologic investigations and giving all the contacts of the patient with a 7-day-long medical observation for temporally related influenza-like illness. Reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for H5 and N1 was applied to test respiratory tract samples and/or throat swabs of the patient and all his contacts specific for the hemagglutinin gene of influenza A H5N1. Activities and strategies such as media response,notification in the public, communications with multiple related sectors, social participation and information exchange with Hong Kong were involved in field control and management. The patient was a male, 31 years old,with an occupation as a truck driver in a factory,and had been residing in Shenzhen for 7 years. Started with an influenza-like syndrome, the patient received treatment on the 4th day of the onset, from a clinic and on the 6th day from a regular hospital. On the 8th day of the disease course, he was confirmed by Shenzhen Center for Disease Control and Prevention as human avian flu case and was then transferred to Intensive Care Unit (ICU). On the 83rd day of commence, the patients was healed and released from the hospital. The patient had no significant exposure to sick poultry or poultry that died from the illness before the onset of the disease. The patient and five family members lived together, but no family member was affected and no contact showed positive results for H5N1. A small food market with live poultry, which was under formal supervision and before illness the patient once visited, located near his apartment. Totally, 35 swabs from live

  14. Strategy and Aspects of Monitoring / Control Strictly in Coordinated Subsystems

    Directory of Open Access Journals (Sweden)

    William José Borges

    2012-06-01

    Full Text Available This paper aims to discuss the approach structures of the strictly coordinated theoretical framework developed by Zylbersztajn and Farina (1999 as an expanded perspective of the firm, taking into account the food supply chains as an extension of the nexus of contracts proposed by Coase (1937 and taken up by Williamson (1985. The structures stand out as strictly coordinated. Zylbersztajn and Farina (1999 turn to identifying points of common interests that encourage firms to promote contracts between themselves in a strictly coordinated way, considering the degree of asset specificity involved in the transaction and the competitive forces that determine the search for strategic positioning organizations to achieve sustainable superior results.

  15. Biosynthesis of Silver Nanoparticles by Marine Invertebrate (Polychaete and Assessment of Its Efficacy against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Reena Singh

    2014-01-01

    Full Text Available Synthesis of metallic nanoparticles by chemical and physical method makes the process often cumbersome due the usage of toxic and expensive chemicals. The present study reports the biosynthesis of silver nanoparticles using marine invertebrate (polychaete extract at room temperature. The ultraviolet-visible (UV-Vis spectroscopy revealed the formation of silver nanoparticles (AgNPs by exhibiting the typical surface plasmon absorption maximum at 418–420 nm. Structure and composition of AgNPs were analyzed by atomic force microscopy (AFM. Average particle size of AgNPs ranged from 40 to 90 nm, confirmed by scanning electron microscopy (SEM analysis. The energy-dispersive X-ray spectroscopy (EDX of the nanoparticles dispersion confirmed the presence of elemental silver signal, whereas X-ray diffraction (XRD substantiated the crystalline nature of synthesized nanoparticle. Fourier transform infrared spectroscopy (FTIR spectral analysis showed the presence of amides phenols, ethers, and fatty acids as major biomolecules responsible for the reduction of silver ions. The possible mechanism responsible for the synthesis of AgNPs by these biomolecules was also illustrated by chemical reactions. The synthesized AgNPs showed comparatively good antibacterial activity against the tested human pathogens. This study advocates that not only plants and microbes but also marine invertebrates do have potential for synthesizing nanoparticles by a cost-effective and eco-friendly approach.

  16. Evidence that the human pathogenic fungus Cryptococcus neoformans var. grubii may have evolved in Africa.

    Directory of Open Access Journals (Sweden)

    Anastasia P Litvintseva

    2011-05-01

    Full Text Available Most of the species of fungi that cause disease in mammals, including Cryptococcus neoformans var. grubii (serotype A, are exogenous and non-contagious. Cryptococcus neoformans var. grubii is associated worldwide with avian and arboreal habitats. This airborne, opportunistic pathogen is profoundly neurotropic and the leading cause of fungal meningitis. Patients with HIV/AIDS have been ravaged by cryptococcosis--an estimated one million new cases occur each year, and mortality approaches 50%. Using phylogenetic and population genetic analyses, we present evidence that C. neoformans var. grubii may have evolved from a diverse population in southern Africa. Our ecological studies support the hypothesis that a few of these strains acquired a new environmental reservoir, the excreta of feral pigeons (Columba livia, and were globally dispersed by the migration of birds and humans. This investigation also discovered a novel arboreal reservoir for highly diverse strains of C. neoformans var. grubii that are restricted to southern Africa, the mopane tree (Colophospermum mopane. This finding may have significant public health implications because these primal strains have optimal potential for evolution and because mopane trees contribute to the local economy as a source of timber, folkloric remedies and the edible mopane worm.

  17. Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans.

    Science.gov (United States)

    Gaur, Manisha; Choudhury, Devapriya; Prasad, Rajendra

    2005-01-01

    The recent completion of the sequencing project of the opportunistic human pathogenic yeast, Candida albicans (http://www.ncbi.nlm.nih.gov/), led us to analyze and classify its ATP-binding cassette (ABC) proteins, which constitute one of the largest superfamilies of proteins. Some of its members are multidrug transporters responsible for the commonly encountered problem of antifungal resistance. TBLASTN searches together with domain analysis identified 81 nucleotide-binding domains, which belong to 51 different putative open reading frames. Considering that each allelic pair represents a single ABC protein of the Candida genome, the total number of putative members of this superfamily is 28. Domain organization, sequence-based analysis and self-organizing map-based clustering led to the classification of Candida ABC proteins into 6 distinct subfamilies. Each subfamily from C. albicans has an equivalent in Saccharomyces cerevisiae suggesting a close evolutionary relationship between the two yeasts. Our searches also led to the identification of a new motif to each subfamily in Candida that could be used to identify sequences from the corresponding subfamily in other organisms. It is hoped that the inventory of Candida ABC transporters thus created will provide new insights into the role of ABC proteins in antifungal resistance as well as help in the functional characterization of the superfamily of these proteins. 2005 S. Karger AG, Basel

  18. Function of the CRISPR-Cas System of the Human Pathogen Clostridium difficile

    Science.gov (United States)

    Boudry, Pierre; Semenova, Ekaterina; Monot, Marc; Datsenko, Kirill A.; Lopatina, Anna; Sekulovic, Ognjen; Ospina-Bedoya, Maicol; Fortier, Louis-Charles; Severinov, Konstantin; Dupuy, Bruno

    2015-01-01

    ABSTRACT Clostridium difficile is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen, C. difficile must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to foreign genetic invaders. Our recent data revealed active expression and processing of CRISPR RNAs from multiple type I-B CRISPR arrays in C. difficile reference strain 630. Here, we demonstrate active expression of CRISPR arrays in strain R20291, an epidemic C. difficile strain. Through genome sequencing and host range analysis of several new C. difficile phages and plasmid conjugation experiments, we provide evidence of defensive function of the CRISPR-Cas system in both C. difficile strains. We further demonstrate that C. difficile Cas proteins are capable of interference in a heterologous host, Escherichia coli. These data set the stage for mechanistic and physiological analyses of CRISPR-Cas-mediated interactions of important global human pathogen with its genetic parasites. PMID:26330515

  19. Deep-sea hydrothermal vent bacteria related to human pathogenic Vibrio species.

    Science.gov (United States)

    Hasan, Nur A; Grim, Christopher J; Lipp, Erin K; Rivera, Irma N G; Chun, Jongsik; Haley, Bradd J; Taviani, Elisa; Choi, Seon Young; Hoq, Mozammel; Munk, A Christine; Brettin, Thomas S; Bruce, David; Challacombe, Jean F; Detter, J Chris; Han, Cliff S; Eisen, Jonathan A; Huq, Anwar; Colwell, Rita R

    2015-05-26

    Vibrio species are both ubiquitous and abundant in marine coastal waters, estuaries, ocean sediment, and aquaculture settings worldwide. We report here the isolation, characterization, and genome sequence of a novel Vibrio species, Vibrio antiquarius, isolated from a mesophilic bacterial community associated with hydrothermal vents located along the East Pacific Rise, near the southwest coast of Mexico. Genomic and phenotypic analysis revealed V. antiquarius is closely related to pathogenic Vibrio species, namely Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio harveyi, and Vibrio vulnificus, but sufficiently divergent to warrant a separate species status. The V. antiquarius genome encodes genes and operons with ecological functions relevant to the environment conditions of the deep sea and also harbors factors known to be involved in human disease caused by freshwater, coastal, and brackish water vibrios. The presence of virulence factors in this deep-sea Vibrio species suggests a far more fundamental role of these factors for their bacterial host. Comparative genomics revealed a variety of genomic events that may have provided an important driving force in V. antiquarius evolution, facilitating response to environmental conditions of the deep sea.

  20. Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus.

    Science.gov (United States)

    Beres, Stephen B; Richter, Ellen W; Nagiec, Michal J; Sumby, Paul; Porcella, Stephen F; DeLeo, Frank R; Musser, James M

    2006-05-02

    In recent years we have studied the relationship between strain genotypes and patient phenotypes in group A Streptococcus (GAS), a model human bacterial pathogen that causes extensive morbidity and mortality worldwide. We have concentrated our efforts on serotype M3 organisms because these strains are common causes of pharyngeal and invasive infections, produce unusually severe invasive infections, and can exhibit epidemic behavior. Our studies have been hindered by the lack of genome-scale phylogenies of multiple GAS strains and whole-genome sequences of multiple serotype M3 strains recovered from individuals with defined clinical phenotypes. To remove some of these impediments, we sequenced to closure the genome of four additional GAS strains and conducted comparative genomic resequencing of 12 contemporary serotype M3 strains representing distinct genotypes and phenotypes. Serotype M3 strains are a single phylogenetic lineage. Strains from asymptomatic throat carriers were significantly less virulent for mice than sterile-site isolates and evolved to a less virulent phenotype by multiple genetic pathways. Strain persistence or extinction between epidemics was strongly associated with presence or absence, respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A serotype M3 clone significantly underrepresented among necrotizing fasciitis cases has a unique frameshift mutation that truncates MtsR, a transcriptional regulator controlling expression of genes encoding iron-acquisition proteins. Expression microarray analysis of this clone confirmed significant alteration in expression of genes encoding iron metabolism proteins. Our analysis provided unprecedented detail about the molecular anatomy of bacterial strain genotype-patient phenotype relationships.

  1. Identification of human proteins that modify misfolding and proteotoxicity of pathogenic ataxin-1.

    Directory of Open Access Journals (Sweden)

    Spyros Petrakis

    Full Text Available Proteins with long, pathogenic polyglutamine (polyQ sequences have an enhanced propensity to spontaneously misfold and self-assemble into insoluble protein aggregates. Here, we have identified 21 human proteins that influence polyQ-induced ataxin-1 misfolding and proteotoxicity in cell model systems. By analyzing the protein sequences of these modifiers, we discovered a recurrent presence of coiled-coil (CC domains in ataxin-1 toxicity enhancers, while such domains were not present in suppressors. This suggests that CC domains contribute to the aggregation- and toxicity-promoting effects of modifiers in mammalian cells. We found that the ataxin-1-interacting protein MED15, computationally predicted to possess an N-terminal CC domain, enhances spontaneous ataxin-1 aggregation in cell-based assays, while no such effect was observed with the truncated protein MED15ΔCC, lacking such a domain. Studies with recombinant proteins confirmed these results and demonstrated that the N-terminal CC domain of MED15 (MED15CC per se is sufficient to promote spontaneous ataxin-1 aggregation in vitro. Moreover, we observed that a hybrid Pum1 protein harboring the MED15CC domain promotes ataxin-1 aggregation in cell model systems. In strong contrast, wild-type Pum1 lacking a CC domain did not stimulate ataxin-1 polymerization. These results suggest that proteins with CC domains are potent enhancers of polyQ-mediated protein misfolding and aggregation in vitro and in vivo.

  2. Transcriptional Regulatory Circuitries in the Human Pathogen Candida albicans Involving Sense–Antisense Interactions

    Science.gov (United States)

    Ahmad, Ausaf; Kravets, Anatoliy; Rustchenko, Elena

    2012-01-01

    Candida albicans, a major human fungal pathogen, usually contains a diploid genome, but controls adaptation to a toxic alternative carbon source L-sorbose, by the reversible loss of one chromosome 5 (Ch5). We have previously identified multiple unique regions on Ch5 that repress the growth on sorbose. In one of the regions, the CSU51 gene determining the repressive property of the region was identified. We report here the identification of the CSU53 gene from a different region on Ch5. Most importantly, we find that CSU51 and CSU53 are associated with novel regulatory elements, ASUs, which are embedded within CSUs in an antisense configuration. ASUs act opposite to CSUs by enhancing the growth on sorbose. In respect to the CSU transcripts, the ASU long antisense transcripts are in lesser amounts, are completely overlapped, and are inversely related. ASUs interact with CSUs in natural CSU/ASU cis configurations, as well as when extra copies of ASUs are placed in trans to the CSU/ASU configurations. We suggest that ASU long embedded antisense transcripts modulate CSU sense transcripts. PMID:22135347

  3. Transcriptional regulatory circuitries in the human pathogen Candida albicans involving sense--antisense interactions.

    Science.gov (United States)

    Ahmad, Ausaf; Kravets, Anatoliy; Rustchenko, Elena

    2012-02-01

    Candida albicans, a major human fungal pathogen, usually contains a diploid genome, but controls adaptation to a toxic alternative carbon source L-sorbose, by the reversible loss of one chromosome 5 (Ch5). We have previously identified multiple unique regions on Ch5 that repress the growth on sorbose. In one of the regions, the CSU51 gene determining the repressive property of the region was identified. We report here the identification of the CSU53 gene from a different region on Ch5. Most importantly, we find that CSU51 and CSU53 are associated with novel regulatory elements, ASUs, which are embedded within CSUs in an antisense configuration. ASUs act opposite to CSUs by enhancing the growth on sorbose. In respect to the CSU transcripts, the ASU long antisense transcripts are in lesser amounts, are completely overlapped, and are inversely related. ASUs interact with CSUs in natural CSU/ASU cis configurations, as well as when extra copies of ASUs are placed in trans to the CSU/ASU configurations. We suggest that ASU long embedded antisense transcripts modulate CSU sense transcripts.

  4. Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans.

    Science.gov (United States)

    Gauthier, Gregory M; Keller, Nancy P

    2013-12-01

    The outbreak of fungal meningitis associated with contaminated methylprednisolone acetate has thrust the importance of fungal infections into the public consciousness. The predominant pathogen isolated from clinical specimens, Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous fungus that infects grasses and rarely humans. This outbreak highlights the potential for fungal pathogens to infect both plants and humans. Most crossover or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota and Mucormycotina phyla. To establish infection, crossover fungi must overcome disparate, host-specific barriers, including protective surfaces (e.g. cuticle, skin), elevated temperature, and immune defenses. This review illuminates the underlying mechanisms used by crossover fungi to cause infection in plants and mammals, and highlights critical events that lead to human infection by these pathogens. Several genes including veA, laeA, and hapX are important in regulating biological processes in fungi important for both invasive plant and animal infections. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Sensitive and rapid RT-qPCR quantification of pathogenic Candida species in human blood.

    Science.gov (United States)

    Ogata, Kiyohito; Matsuda, Kazunori; Tsuji, Hirokazu; Nomoto, Koji

    2015-10-01

    For accurate diagnosis and appropriate treatment of candidiasis, we developed a highly sensitive quantitative RT-PCR (RT-qPCR) system for five Candida species that have been reported to be the major causes of bloodstream fungal infection (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei), together with a system for all pathogenic Candida species. Cells of each fungal species spiked into human peripheral blood (PB) were specifically detected at a lower detection limit of 10(0) cell/1 mL PB by this system using the newly developed specific primer sets targeting 18S or 26S rRNA of the five Candida species, together with the existing group primer set. The total count of the five Candida spp. as the sum of those obtained by using the five species primer sets was equivalent to the count obtained by using the group primer set, indicating that the group set covered the major five Candida spp. in human blood with the same degree of accuracy as the species primer sets. The RT-qPCR counts of the Candida species were in good agreement with CFU counts obtained by their culture on CHROMagar™, with a lower detection limit of 10(0)cell/mL of PB. Candida rRNA molecules were stably stored for at least 7 days at 4°C by keeping the blood specimens in an RNA stabilizing reagent. These results strongly suggest that this sensitive system is useful for accurate and rapid diagnosis of Candida bloodstream infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Molecular viability testing of bacterial pathogens from a complex human sample matrix.

    Directory of Open Access Journals (Sweden)

    Kris M Weigel

    Full Text Available Assays for bacterial ribosomal RNA precursors (pre-rRNA have been shown to distinguish viable from inactivated bacterial cells in drinking water samples. Because the synthesis of pre-rRNA is rapidly induced by nutritional stimulation, viable bacteria can be distinguished from inactivated cells and free nucleic acids by measuring the production of species-specific pre-rRNA in samples that have been briefly stimulated with nutrients. Here, pre-rRNA analysis was applied to bacteria from serum, a human sample matrix. In contrast to drinking water, serum is rich in nutrients that might be expected to mask the effects of nutritional stimulation. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR assays were used to detect pre-rRNA of four bacterial species: Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, and the Mycobacterium tuberculosis complex. These species were chosen for their clinical significance and phylogenetic diversity (Proteobacteria, Firmicutes, and Actinobacteria. To maximize resolving power, pre-rRNA was normalized to genomic DNA of each pathogen. When viable cells were shifted from serum to bacteriological culture medium, rapid replenishment of pre-rRNA was always observed. Cells of P. aeruginosa that were inactivated in the presence of serum exhibited no pre-rRNA response to nutritional stimulation, despite strong genomic DNA signals in these samples. When semi-automated methods were used, pre-rRNA analysis detected viable A. baumannii cells in serum at densities of ≤100 CFU/mL in <5.5 hours. Originally developed for rapid microbiological analysis of drinking water, ratiometric pre-rRNA analysis can also assess the viability of bacterial cells derived from human specimens, without requiring bacteriological culture.

  7. Strict finitism and the logic of mathematical applications

    CERN Document Server

    Ye, Feng

    2011-01-01

    Exploring the logic behind applied mathematics to the physical world, this volume illustrates how radical naturalism, nominalism and strict finitism can account for the applications of classical mathematics in current theories about natural phenomena.

  8. Strict monotonicity and unique continuation of the biharmonic operator

    Directory of Open Access Journals (Sweden)

    Najib Tsouli

    2012-01-01

    Full Text Available In this paper, we will show that the strict monotonicity of the eigenvalues of the biharmonic operator holds if and only if some unique continuation property is satisfied by the corresponding eigenfunctions.

  9. Human infection with highly pathogenic H5N1 influenza virus

    NARCIS (Netherlands)

    Gambotto, Andrea; Barratt-Boyes, Simon M.; de Jong, Menno D.; Neumann, Gabriele; Kawaoka, Yoshihiro

    2008-01-01

    Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of

  10. Draft Genome Sequence of the Human-Pathogenic Fungus Scedosporium boydii

    OpenAIRE

    Duvaux, Ludovic; Shiller, Jason; Vandeputte, Patrick; Dug? de Bernonville, Thomas; Thornton, Christopher; Papon, Nicolas; Le Cam, Bruno; Bouchara, Jean-Philippe; Gastebois, Amandine

    2017-01-01

    ABSTRACT The opportunistic fungal pathogen Scedosporium boydii is the most common Scedosporium species in French patients with cystic fibrosis. Here we present the first genome report for S.?boydii, providing a resource which may enable the elucidation of the pathogenic mechanisms in this species.

  11. Neglected pathogens: bacterial infections in persons with human immunodeficiency virus infection. A review of the literature (1).

    Science.gov (United States)

    Fish, D N; Danziger, L H

    1993-01-01

    Bacterial infections, including those that cause infection in the healthy host as well as those that are more opportunistic, occur very commonly among persons infected with the human immunodeficiency virus (HIV). Bacterial infections are a direct result of the severe humoral and cellular immune defects found in these patients. Epidemiologic factors such as intravenous drug use and stage of HIV infection may also play important roles. Pulmonary, bloodstream, gastrointestinal, central nervous system, skin and soft tissue, and catheter-related infections are common, as are endocarditis, prostatitis, and others. Frequently reported pathogens are common organisms such as Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, and enteric gram-negative pathogens, as well as less typical ones such as Listeria monocytogenes and Nocardia sp. The frequency of infection is specific to organ system and pathogen, often being many times higher than in immunocompetent hosts. Prompt recognition and aggressive therapy are required to reduce morbidity and mortality due to these infections.

  12. Two examples of non strictly convex large deviations

    OpenAIRE

    De Marco, Stefano; Jacquier, Antoine; Roome, Patrick

    2016-01-01

    We present two examples of a large deviations principle where the rate function is not strictly convex. This is motivated by a model used in mathematical finance (the Heston model), and adds a new item to the zoology of non strictly convex large deviations. For one of these examples, we show that the rate function of the Cramer-type of large deviations coincides with that of the Freidlin-Wentzell when contraction principles are applied.

  13. Concurrent Detection of Human Norovirus and Bacterial Pathogens in Water Samples from an Agricultural Region in Central California Coast

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    Peng Tian

    2017-08-01

    Full Text Available Bacterial pathogens and human norovirus (HuNoV are major cause for acute gastroenteritis caused by contaminated food and water. Public waterways can become contaminated from a variety of sources and flood after heavy rain events, leading to pathogen contamination of produce fields. We initiated a survey of several public watersheds in a major leafy green produce production region of the Central California Coast to determine the prevalence of HuNoV as well as bacterial pathogens. Moore swabs were used to collect environmental samples bi-monthly at over 30 sampling sites in the region. High prevalence of HuNoV and bacterial pathogens were detected in environmental water samples in the region. The overall detection rates of HuNoV, O157 Shiga toxin-producing Escherichia coli (STEC, non-O157 STEC, Salmonella, and Listeria were 25.58, 7.91, 9.42, 59.65, and 44.30%, respectively. The detection rates of Salmonella and L. monocytogenes were significantly higher in the spring. Fall and spring had elevated detection rates of O157 STEC. The overall detection rates of non-O157 STEC in the fall were lower than the other seasons but not significant. The overall detection rates of HuNoV were highest in fall, followed by spring and winter, with summer being lowest and significantly lower than other seasons. This study presented the first study of evaluating the correlation between the detection rate of HuNoV and the detection rates of four bacterial pathogens from environmental water. Overall, there was no significant difference in HuNoV detection rates between samples testing positive or negative for the four bacterial pathogens tested. Pathogens in animal-impacted and human-impacted areas were investigated. There were significant higher detection rates in animal-impacted areas than that of human-impacted areas for bacterial pathogens. However, there was no difference in HuNoV detection rates between these two areas. The overall detection levels of generic E

  14. Strictly contractive quantum channels and physically realizable quantum computers

    International Nuclear Information System (INIS)

    Raginsky, Maxim

    2002-01-01

    We study the robustness of quantum computers under the influence of errors modeled by strictly contractive channels. A channel T is defined to be strictly contractive if, for any pair of density operators ρ, σ in its domain, parallel Tρ-Tσ parallel 1 ≤k parallel ρ-σ parallel 1 for some 0≤k 1 denotes the trace norm). In other words, strictly contractive channels render the states of the computer less distinguishable in the sense of quantum detection theory. Starting from the premise that all experimental procedures can be carried out with finite precision, we argue that there exists a physically meaningful connection between strictly contractive channels and errors in physically realizable quantum computers. We show that, in the absence of error correction, sensitivity of quantum memories and computers to strictly contractive errors grows exponentially with storage time and computation time, respectively, and depends only on the constant k and the measurement precision. We prove that strict contractivity rules out the possibility of perfect error correction, and give an argument that approximate error correction, which covers previous work on fault-tolerant quantum computation as a special case, is possible

  15. Low Prevalence of Human Pathogens on Fresh Produce on Farms and in Packing Facilities: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Amelia E. Van Pelt

    2018-02-01

    Full Text Available Foodborne illness burdens individuals around the world and may be caused by consuming fresh produce contaminated with bacterial, parasite, and viral pathogens. Pathogen contamination on produce may originate at the farm and packing facility. This research aimed to determine the prevalence of human pathogens (bacteria, parasites, and viruses on fresh produce (fruits, herbs, and vegetables on farms and in packing facilities worldwide through a systematic review of 38 peer-reviewed articles. The median and range of the prevalence was calculated, and Kruskal–Wallis tests and logistic regression were performed to compare prevalence among pooled samples of produce groups, pathogen types, and sampling locations. Results indicated a low median percentage of fresh produce contaminated with pathogens (0%. Both viruses (p-value = 0.017 and parasites (p-value = 0.033, on fresh produce, exhibited higher prevalence than bacteria. No significant differences between fresh produce types or between farm and packing facility were observed. These results may help to better quantify produce contamination in the production environment and inform strategies to prevent future foodborne illness.

  16. Genome sequence of human adenovirus type 55, a re-emergent acute respiratory disease pathogen in China.

    Science.gov (United States)

    Zhang, Qiwei; Seto, Donald; Cao, Bin; Zhao, Suhui; Wan, Chengsong

    2012-11-01

    Human adenovirus type 55 (HAdV-B55) is an acute respiratory disease (ARD) pathogen first completely characterized in China (2006). This is a unique Trojan horse microbe with the virus neutralization attribute of a renal pathogen and the cell tropism and clinical attributes of a respiratory pathogen, bypassing herd immunity. It appeared to be an uncommon pathogen, with earlier putative, sporadic occurrences in Spain (1969) and Turkey (2004); these isolates were incompletely characterized using only two epitopes. Reported here is the genome of a second recent isolate (China, 2011), indicating that it may occur more frequently. The availability of this HAdV-B55 genome provides a foundation for studying adenovirus molecular evolution, the dynamics of epidemics, and patterns of pathogen emergence and re-emergence. These data facilitate studies to predict genome recombination between adenoviruses, as well as sequence divergence rates and hotspots, all of which are important for vaccine development and because HAdVs are used for epitope and/or gene delivery vectors.

  17. Transition metals at the host–pathogen interface: How Neisseria exploit human metalloproteins for acquiring iron and zinc

    Science.gov (United States)

    Neumann, Wilma; Hadley, Rose C.; Nolan, Elizabeth M.

    2017-01-01

    Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important variable for whether infection occurs. One strategy bacterial pathogens employ to overcome metal restriction involves hijacking abundant host metalloproteins. The obligate human pathogens Neisseria spp. express TonB-dependent transport systems that capture human metalloproteins, extract the bound metal ions, and deliver these nutrients into the bacterial cell. This Essay highlights structural and mechanistic investigations that provide insights into how Neisseria acquire iron from the Fe(III)-transport protein transferrin, the Fe(III)-chelating host-defense protein lactoferrin, and the oxygen-transport protein hemoglobin, and obtain zinc from the metal-sequestering antimicrobial protein calprotectin. PMID:28487398

  18. Dispersal of human and plant pathogens biofilms via nitric oxide donors at 4 °C.

    Science.gov (United States)

    Marvasi, Massimiliano; Durie, Ian A; Henríquez, Tania; Satkute, Aiste; Matuszewska, Marta; Prado, Raphael Carvalho

    2016-12-01

    Recent studies suggest that nitric oxide donors capable of manipulating nitric oxide-mediated signaling in bacteria could induce dispersal of biofilms. Encased in extracellular polymeric substances, human and plant pathogens within biofilms are significantly more resistant to sanitizers. This is particularly a problem in refrigerated environments where food is processed. In an exercise aimed to study the potential of nitric oxide donors as biofilm dispersal in refrigerated conditions, we compared the ability of different nitric oxide donors (SNAP, NO-aspirin and Noc-5) to dislodge biofilms formed by foodborne, human and plant pathogens treated at 4 °C. The donors SNAP and Noc-5 were efficient in dispersing biofilms formed by Salmonella enterica, pathogenic Escherichia coli and Listeria innocua. The biomasses were decreased up to 30 % when compared with the untreated controls. When the plant pathogens Pectobacterium sp. and Xanthomonas sp. were tested the dispersion was mainly limited to Pectobacterium carotovorum biofilms, decreasing up to 15 % after exposure to molsidomine. Finally, the association of selected nitric oxide donors with sanitizers (DiQuat, H2O2, peracetic acid and PhenoTek II) was effective in dispersing biofilms. The best dispersal was achieved by pre-treating P. carotovorum with molsidomine and then peracetic acid. The synergistic effect was estimated up to ~35 % in dispersal when compared with peracetic acid alone. The association of nitric oxide donors with sanitizers could provide a foundation for an improved sanitization procedure for cleaning refrigerate environments.

  19. Overlapped sequence types (STs and serogroups of avian pathogenic (APEC and human extra-intestinal pathogenic (ExPEC Escherichia coli isolated in Brazil.

    Directory of Open Access Journals (Sweden)

    Renato Pariz Maluta

    Full Text Available Avian pathogenic Escherichia coli (APEC strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153 and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011. Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7% were contained in one cluster while most APEC strains (63.2% segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC, presented more than 70% of similarity by PFGE. The results demonstrate that some "zoonotic-related" STs (ST117, ST131, ST10CC, ST23CC are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.

  20. Overlapped sequence types (STs) and serogroups of avian pathogenic (APEC) and human extra-intestinal pathogenic (ExPEC) Escherichia coli isolated in Brazil.

    Science.gov (United States)

    Maluta, Renato Pariz; Logue, Catherine Mary; Casas, Monique Ribeiro Tiba; Meng, Ting; Guastalli, Elisabete Aparecida Lopes; Rojas, Thaís Cabrera Galvão; Montelli, Augusto Cezar; Sadatsune, Teruê; de Carvalho Ramos, Marcelo; Nolan, Lisa Kay; da Silveira, Wanderley Dias

    2014-01-01

    Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some "zoonotic-related" STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.

  1. Haemophilus influenzae: using comparative genomics to accurately identify a highly recombinogenic human pathogen.

    Science.gov (United States)

    Price, Erin P; Sarovich, Derek S; Nosworthy, Elizabeth; Beissbarth, Jemima; Marsh, Robyn L; Pickering, Janessa; Kirkham, Lea-Ann S; Keil, Anthony D; Chang, Anne B; Smith-Vaughan, Heidi C

    2015-08-27

    Haemophilus influenzae is an opportunistic bacterial pathogen that exclusively colonises humans and is associated with both acute and chronic disease. Despite its clinical significance, accurate identification of H. influenzae is a non-trivial endeavour. H. haemolyticus can be misidentified as H. influenzae from clinical specimens using selective culturing methods, reflecting both the shared environmental niche and phenotypic similarities of these species. On the molecular level, frequent genetic exchange amongst Haemophilus spp. has confounded accurate identification of H. influenzae, leading to both false-positive and false-negative results with existing speciation assays. Whole-genome single-nucleotide polymorphism data from 246 closely related global Haemophilus isolates, including 107 Australian isolate genomes generated in this study, were used to construct a whole-genome phylogeny. Based on this phylogeny, H. influenzae could be differentiated from closely related species. Next, a H. influenzae-specific locus, fucP, was identified, and a novel TaqMan real-time PCR assay targeting fucP was designed. PCR specificity screening across a panel of clinically relevant species, coupled with in silico analysis of all species within the order Pasteurellales, demonstrated that the fucP assay was 100 % specific for H. influenzae; all other examined species failed to amplify. This study is the first of its kind to use large-scale comparative genomic analysis of Haemophilus spp. to accurately delineate H. influenzae and to identify a species-specific molecular signature for this species. The fucP assay outperforms existing H. influenzae targets, most of which were identified prior to the next-generation genomics era and thus lack validation across a large number of Haemophilus spp. We recommend use of the fucP assay in clinical and research laboratories for the most accurate detection and diagnosis of H. influenzae infection and colonisation.

  2. A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains

    Directory of Open Access Journals (Sweden)

    Cody J. Buchanan

    2017-06-01

    Full Text Available Campylobacter jejuni is a leading human enteric pathogen worldwide and despite an improved understanding of its biology, ecology, and epidemiology, limited tools exist for identifying strains that are likely to cause disease. In the current study, we used subtyping data in a database representing over 24,000 isolates collected through various surveillance projects in Canada to identify 166 representative genomes from prevalent C. jejuni subtypes for whole genome sequencing. The sequence data was used in a genome-wide association study (GWAS aimed at identifying accessory gene markers associated with clinically related C. jejuni subtypes. Prospective markers (n = 28 were then validated against a large number (n = 3,902 of clinically associated and non-clinically associated genomes from a variety of sources. A total of 25 genes, including six sets of genetically linked genes, were identified as robust putative diagnostic markers for clinically related C. jejuni subtypes. Although some of the genes identified in this study have been previously shown to play a role in important processes such as iron acquisition and vitamin B5 biosynthesis, others have unknown function or are unique to the current study and warrant further investigation. As few as four of these markers could be used in combination to detect up to 90% of clinically associated isolates in the validation dataset, and such markers could form the basis for a screening assay to rapidly identify strains that pose an increased risk to public health. The results of the current study are consistent with the notion that specific groups of C. jejuni strains of interest are defined by the presence of specific accessory genes.

  3. Nitrogen Metabolite Repression of Metabolism and Virulence in the Human Fungal Pathogen Cryptococcus neoformans

    Science.gov (United States)

    Lee, I. Russel; Chow, Eve W. L.; Morrow, Carl A.; Djordjevic, Julianne T.; Fraser, James A.

    2011-01-01

    Proper regulation of metabolism is essential to maximizing fitness of organisms in their chosen environmental niche. Nitrogen metabolite repression is an example of a regulatory mechanism in fungi that enables preferential utilization of easily assimilated nitrogen sources, such as ammonium, to conserve resources. Here we provide genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen Cryptococcus neoformans. In addition to loss of transcriptional activation of catabolic enzyme-encoding genes of the uric acid and proline assimilation pathways in the presence of ammonium, nitrogen metabolite repression also regulates the production of the virulence determinants capsule and melanin. Since GATA transcription factors are known to play a key role in nitrogen metabolite repression, bioinformatic analyses of the C. neoformans genome were undertaken and seven predicted GATA-type genes were identified. A screen of these deletion mutants revealed GAT1, encoding the only global transcription factor essential for utilization of a wide range of nitrogen sources, including uric acid, urea, and creatinine—three predominant nitrogen constituents found in the C. neoformans ecological niche. In addition to its evolutionarily conserved role in mediating nitrogen metabolite repression and controlling the expression of catabolic enzyme and permease-encoding genes, Gat1 also negatively regulates virulence traits, including infectious basidiospore production, melanin formation, and growth at high body temperature (39°–40°). Conversely, Gat1 positively regulates capsule production. A murine inhalation model of cryptococcosis revealed that the gat1Δ mutant is slightly more virulent than wild type, indicating that Gat1 plays a complex regulatory role during infection. PMID:21441208

  4. Gene Function Analysis in the Ubiquitous Human Commensal and Pathogen Malassezia Genus.

    Science.gov (United States)

    Ianiri, Giuseppe; Averette, Anna F; Kingsbury, Joanne M; Heitman, Joseph; Idnurm, Alexander

    2016-11-29

    The genus Malassezia includes 14 species that are found on the skin of humans and animals and are associated with a number of diseases. Recent genome sequencing projects have defined the gene content of all 14 species; however, to date, genetic manipulation has not been possible for any species within this genus. Here, we develop and then optimize molecular tools for the transformation of Malassezia furfur and Malassezia sympodialis using Agrobacterium tumefaciens delivery of transfer DNA (T-DNA) molecules. These T-DNAs can insert randomly into the genome. In the case of M. furfur, targeted gene replacements were also achieved via homologous recombination, enabling deletion of the ADE2 gene for purine biosynthesis and of the LAC2 gene predicted to be involved in melanin biosynthesis. Hence, the introduction of exogenous DNA and direct gene manipulation are feasible in Malassezia species. Species in the genus Malassezia are a defining component of the microbiome of the surface of mammals. They are also associated with a wide range of skin disease symptoms. Many species are difficult to culture in vitro, and although genome sequences are available for the species in this genus, it has not been possible to assess gene function to date. In this study, we pursued a series of possible transformation methods and identified one that allows the introduction of DNA into two species of Malassezia, including the ability to make targeted integrations into the genome such that genes can be deleted. This research opens a new direction in terms of now being able to analyze gene functions in this little understood genus. These tools will contribute to define the mechanisms that lead to the commensalism and pathogenicity in this group of obligate fungi that are predominant on the skin of mammals. Copyright © 2016 Ianiri et al.

  5. Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome.

    Directory of Open Access Journals (Sweden)

    Biju Joseph

    Full Text Available BACKGROUND: Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH and multilocus sequence typing (MLST of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. PRINCIPAL FINDINGS: We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. CONCLUSIONS: Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.

  6. The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution.

    Directory of Open Access Journals (Sweden)

    Nikolay G Kolev

    2010-09-01

    Full Text Available The genome of Trypanosoma brucei, the causative agent of African trypanosomiasis, was published five years ago, yet identification of all genes and their transcripts remains to be accomplished. Annotation is challenged by the organization of genes transcribed by RNA polymerase II (Pol II into long unidirectional gene clusters with no knowledge of how transcription is initiated. Here we report a single-nucleotide resolution genomic map of the T. brucei transcriptome, adding 1,114 new transcripts, including 103 non-coding RNAs, confirming and correcting many of the annotated features and revealing an extensive heterogeneity of 5' and 3' ends. Some of the new transcripts encode polypeptides that are either conserved in T. cruzi and Leishmania major or were previously detected in mass spectrometry analyses. High-throughput RNA sequencing (RNA-Seq was sensitive enough to detect transcripts at putative Pol II transcription initiation sites. Our results, as well as recent data from the literature, indicate that transcription initiation is not solely restricted to regions at the beginning of gene clusters, but may occur at internal sites. We also provide evidence that transcription at all putative initiation sites in T. brucei is bidirectional, a recently recognized fundamental property of eukaryotic promoters. Our results have implications for gene expression patterns in other important human pathogens with similar genome organization (Trypanosoma cruzi, Leishmania sp. and revealed heterogeneity in pre-mRNA processing that could potentially contribute to the survival and success of the parasite population in the insect vector and the mammalian host.

  7. Methanolic Extract of Plumbago Zeylanica - A Remarkable Antibacterial Agent Against Many Human and Agricultural Pathogens

    Directory of Open Access Journals (Sweden)

    Mukesh Kumar Singh

    2017-03-01

    Full Text Available Objectives: The current investigation was carried out to determine the cytotoxic and the antimicrobial activities of methanolic extracts of Plumbago zeylanica. Methods: The stems, leaves, and whole plants were air dried and extracted with methanol by using a Soxhlet extractor for 72 hours at 55 - 60°C. The antimicrobial activities were determined from the zones of inhibition, which were measured by using the agar well diffusion method, and the cytotoxicity assays were performed using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay method. Results: The methanolic extracts of the stem and the leaves of Plumbago zeylanica were tested against six bacterial species and nine fungal species, and both extracts showed antimicrobial activity in a dose-dependent manner. The leaf extract of Plumbago zeylanica showed maximum antimicrobial activity against both Staphylococcus aureus sub sp aureus and Fusarium oxysporum. The stem extract was found to be more antimicrobial against the Pseudomonas aeruginosa and the Penicillium expansum species. MTT assays were used to test the cytotoxicity of the whole plant extract in the HCT-116 and the K-562 cell lines, and that extract was shown to have weak cytotoxicity in both cell lines. Conclusion: In the present study, the methanolic stem extracts of Plumbago zeylanica were found to possess remarkable antibacterial activities against many human and agricultural pathogens. The extracts were also found to possess significant antifungal activities, but the antifungal activities were less than the antibacterial activities. Finally, the extracts were found to have weak cytotoxicities in the HCT-116 and the K-562 cell lines.

  8. Molecular Detection of Tick-Borne Pathogens in Humans with Tick Bites and Erythema Migrans, in the Netherlands.

    Directory of Open Access Journals (Sweden)

    Setareh Jahfari

    2016-10-01

    Full Text Available Tick-borne diseases are the most prevalent vector-borne diseases in Europe. Knowledge on the incidence and clinical presentation of other tick-borne diseases than Lyme borreliosis and tick-borne encephalitis is minimal, despite the high human exposure to these pathogens through tick bites. Using molecular detection techniques, the frequency of tick-borne infections after exposure through tick bites was estimated.Ticks, blood samples and questionnaires on health status were collected from patients that visited their general practitioner with a tick bite or erythema migrans in 2007 and 2008. The presence of several tick-borne pathogens in 314 ticks and 626 blood samples of this cohort were analyzed using PCR-based methods. Using multivariate logistic regression, associations were explored between pathogens detected in blood and self-reported symptoms at enrolment and during a three-month follow-up period.Half of the ticks removed from humans tested positive for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, Rickettsia monacensis, Borrelia miyamotoi and several Babesia species. Among 92 Borrelia burgdorferi s. l. positive ticks, 33% carried another pathogen from a different genus. In blood of sixteen out of 626 persons with tick bites or erythema migrans, DNA was detected from Candidatus Neoehrlichia mikurensis (n = 7, Anaplasma phagocytophilum (n = 5, Babesia divergens (n = 3, Borrelia miyamotoi (n = 1 and Borrelia burgdorferi s. l. (n = 1. None of these sixteen individuals reported any overt symptoms that would indicate a corresponding illness during the three-month follow-up period. No associations were found between the presence of pathogen DNA in blood and; self-reported symptoms, with pathogen DNA in the corresponding ticks (n = 8, reported tick attachment duration, tick engorgement, or antibiotic treatment at enrolment.Based on molecular detection techniques, the

  9. Molecular Detection of Tick-Borne Pathogens in Humans with Tick Bites and Erythema Migrans, in the Netherlands.

    Science.gov (United States)

    Jahfari, Setareh; Hofhuis, Agnetha; Fonville, Manoj; van der Giessen, Joke; van Pelt, Wilfrid; Sprong, Hein

    2016-10-01

    Tick-borne diseases are the most prevalent vector-borne diseases in Europe. Knowledge on the incidence and clinical presentation of other tick-borne diseases than Lyme borreliosis and tick-borne encephalitis is minimal, despite the high human exposure to these pathogens through tick bites. Using molecular detection techniques, the frequency of tick-borne infections after exposure through tick bites was estimated. Ticks, blood samples and questionnaires on health status were collected from patients that visited their general practitioner with a tick bite or erythema migrans in 2007 and 2008. The presence of several tick-borne pathogens in 314 ticks and 626 blood samples of this cohort were analyzed using PCR-based methods. Using multivariate logistic regression, associations were explored between pathogens detected in blood and self-reported symptoms at enrolment and during a three-month follow-up period. Half of the ticks removed from humans tested positive for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis, Rickettsia helvetica, Rickettsia monacensis, Borrelia miyamotoi and several Babesia species. Among 92 Borrelia burgdorferi s. l. positive ticks, 33% carried another pathogen from a different genus. In blood of sixteen out of 626 persons with tick bites or erythema migrans, DNA was detected from Candidatus Neoehrlichia mikurensis (n = 7), Anaplasma phagocytophilum (n = 5), Babesia divergens (n = 3), Borrelia miyamotoi (n = 1) and Borrelia burgdorferi s. l. (n = 1). None of these sixteen individuals reported any overt symptoms that would indicate a corresponding illness during the three-month follow-up period. No associations were found between the presence of pathogen DNA in blood and; self-reported symptoms, with pathogen DNA in the corresponding ticks (n = 8), reported tick attachment duration, tick engorgement, or antibiotic treatment at enrolment. Based on molecular detection techniques, the probability of

  10. Computational Analysis of Host-Pathogen Protein Interactions between Humans and Different Strains of EnterohemorrhagicEscherichia coli.

    Science.gov (United States)

    Bose, Tungadri; Venkatesh, K V; Mande, Sharmila S

    2017-01-01

    Serotype O157:H7, an enterohemorrhagic Escherichia coli (EHEC), is known to cause gastrointestinal and systemic illnesses ranging from diarrhea and hemorrhagic colitis to potentially fatal hemolytic uremic syndrome. Specific genetic factors like ompA, nsrR , and LEE genes are known to play roles in EHEC pathogenesis. However, these factors are not specific to EHEC and their presence in several non-pathogenic strains indicates that additional factors are involved in pathogenicity. We propose a comprehensive effort to screen for such potential genetic elements, through investigation of biomolecular interactions between E. coli and their host. In this work, an in silico investigation of the protein-protein interactions (PPIs) between human cells and four EHEC strains (viz., EDL933, Sakai, EC4115, and TW14359) was performed in order to understand the virulence and host-colonization strategies of these strains. Potential host-pathogen interactions (HPIs) between human cells and the "non-pathogenic" E. coli strain MG1655 were also probed to evaluate whether and how the variations in the genomes could translate into altered virulence and host-colonization capabilities of the studied bacterial strains. Results indicate that a small subset of HPIs are unique to the studied pathogens and can be implicated in virulence. This subset of interactions involved E. coli proteins like YhdW, ChuT, EivG, and HlyA. These proteins have previously been reported to be involved in bacterial virulence. In addition, clear differences in lineage and clade-specific HPI profiles could be identified. Furthermore, available gene expression profiles of the HPI-proteins were utilized to estimate the proportion of proteins which may be involved in interactions. We hypothesized that a cumulative score of the ratios of bound:unbound proteins (involved in HPIs) would indicate the extent of colonization. Thus, we designed the Host Colonization Index (HCI) measure to determine the host colonization

  11. Identification of Discriminating Metabolic Pathways and Metabolites in Human PBMCs Stimulated by Various Pathogenic Agents

    NARCIS (Netherlands)

    Zhang, Xiang; Mardinoglu, Adil; Joosten, Leo A. B.; Kuivenhoven, Jan A.; Li, Yang; Netea, Mihai G.; Groen, Albert K.

    2018-01-01

    Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by

  12. Low prevalence of human pathogens on fresh produce on farms and in packing facilities

    Science.gov (United States)

    Foodborne illness burdens individuals around the world. Consumption of produce contaminated with bacterial, parasite, and viral pathogens causes a significant proportion of cases of foodborne illness. Farms and packing facilities provide opportunities for contamination. This research aimed to determ...

  13. Metal-homeostasis in the pathobiology of the opportunistic human fungal pathogen Aspergillus fumigatus.

    Science.gov (United States)

    Blatzer, Michael; Latgé, Jean-Paul

    2017-12-01

    In contrast to obligate pathogens opportunistic pathogens such as Aspergillus fumigatus do not need a specific host to propagate or survive. However several characteristics of the saprophytic life-style and the selective pressure encountered in the primary ecological niche contribute to the virulence of A. fumigatus. All fungi depend on metals for growth and proliferation, like iron, copper, zinc, manganese or calcium. In the recent past several studies explored the manifold impact of metals modulating virulence of pathogens. Components which might be scarce in the natural environment but also in the host due to nutritional immunity. This review recapitulates molecular constituents of metal ion uptake systems in A. fumigatus, their regulation and their significance at the host-pathogen battlefield. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Cross-species infection of specific-pathogen-free pigs by a genotype 4 strain of human hepatitis E virus

    Science.gov (United States)

    Feagins, A. R.; Opriessnig, T.; Huang, Y. W.; Halbur, P. G.; Meng, X. J.

    2010-01-01

    SUMMARY Hepatitis E virus (HEV) is an important pathogen. The animal strain of HEV, swine HEV, is related to human HEV. The genotype 3 swine HEV infected humans and genotype 3 human HEV infected pigs. The genotype 4 swine and human HEV strains are genetically related, but it is unknown whether genotype 4 human HEV can infect pigs. A swine bioassay was utilized in this study to determine whether genotype 4 human HEV can infect pigs. Fifteen, 4-week-old, specific-pathogen-free pigs were divided into 3 groups of 5 each. Group 1 pigs were each inoculated intravenously with PBS buffer as negative controls, group 2 pigs similarly with genotype 3 human HEV (strain US-2), and group 3 pigs similarly with genotype 4 human HEV (strain TW6196E). Serum and fecal samples were collected at 0, 7, 14, 21, 28, 35, 42, 49, and 56 days postinoculation (dpi) and tested for evidence of HEV infection. All pigs were necropsied at 56 dpi. As expected, the negative control pigs remained negative. The positive control pigs inoculated with genotype 3 human HEV all became infected as evidenced by detection of HEV antibodies, viremia and fecal virus shedding. All five pigs in group 3 inoculated with genotype 4 human HEV also became infected: fecal virus shedding and viremia were detected variably from 7 to 56 dpi, and seroconversion occurred by 28 dpi. The data indicated that genotype 4 human HEV has an expanded host range, and the results have important implications for understanding the natural history and zoonosis of HEV. PMID:18551597

  15. In vitro antibacterial activity of venom protein isolated from sea snake Enhydrina schistosa against drugresistant human pathogenic bacterial strains

    Directory of Open Access Journals (Sweden)

    Palani Damotharan

    2015-06-01

    Full Text Available Objective: To evaluate the antibacterial activity of sea snake (Enhydrina schistosa venom protein against drug-resistant human pathogenic bacterial strains. Methods: The venom was collected by milking process from the live specimens of sea snake are using capillary tubes or glass plates. Venom was purified by ion exchange chromatography and it was tested for in-vitro antibacterial activity against 10 drug-resistant human pathogenic bacterial strains using the standard disc diffusion method. Results: The notable antibacterial activity was observed at 150 µg/mL concentration of purified venom and gave its minimum inhibitory concentrations values exhibited between 200-100 µg/mL against all the tested bacterial strains. The maximum zone of inhibition was observed at 16.4 mm against Salmonella boydii and the minimum activity was observed at 7.5 mm against Pseudomonas aeruginosa. After the sodium-dodecyl-sulfate-polyacrylamide gel electrophoresis there were a clear single band was detected in the gel that corresponding to purified venom protein molecular weight of 44 kDa. Conclusions: These results suggested that the sea snake venom might be a feasible source for searching potential antibiotics agents against human pathogenic diseases.

  16. Within-batch prevalence and quantification of human pathogenic Yersinia enterocolitica and Y. pseudotuberculosis in tonsils of pigs at slaughter.

    Science.gov (United States)

    Vanantwerpen, Gerty; Van Damme, Inge; De Zutter, Lieven; Houf, Kurt

    2014-03-14

    Yersiniosis is a common bacterial zoonosis in Europe and healthy pigs are known to be the primary reservoir of human pathogenic Yersinia enterocolitica and Y. pseudotuberculosis. However, little information is available about the prevalence of these pathogens within pig batches at time of slaughter. The tonsils of 7047 fattening pigs, belonging to 100 farms, were aseptically collected immediately after evisceration in two Belgian slaughterhouses. The batch size varied between 70 and 930 pigs. On average, 70 pigs were sampled per batch. The tonsils were examined by direct plating on cefsulodin-irgasan-novobiocin (CIN) agar plates and the number of suspect Yersinia colonies was counted. Pathogenic Y. enterocolitica serotype O:3 were found in tonsils of 2009 pigs (28.5%), originating from 85 farms. The within-batch prevalence in positive farms ranged from 5.1 to 64.4%. The number of Y. enterocolitica in positive pigs varied between 2.01 and 5.98 log10 CFU g(-1) tonsil, with an average of 4.00 log10 CFU g(-1) tonsil. Y. pseudotuberculosis was found in seven farms, for which the within-batch prevalence varied from 2 to 10%. In five of these farms, both Y. enterocolitica and Y. pseudotuberculosis were simultaneously present. Human pathogenic Yersinia spp. are widespread in slaughter pig batches in Belgium as 87% of the tested batches were infected with these pathogens at the time of slaughter. The large variation of the prevalence between batches may lead to different levels of contamination of carcasses and risks for public health. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effect of the vitamin B12-binding protein haptocorrin present in human milk on a panel of commensal and pathogenic bacteria

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Laursen, Martin Frederik; Lildballe, Dorte L.

    2011-01-01

    commensal and pathogenic bacteria to which infants are likely to be exposed. Well-diffusion assays addressing antibacterial effects were performed with human milk, haptocorrin-free human milk, porcine holo-haptocorrin (saturated with B-12) and human apo-haptocorrin (unsaturated). Human milk inhibited...

  18. Convergence theorems for strictly hemi-contractive maps

    International Nuclear Information System (INIS)

    Chidume, C.E.; Osilike, M.O.

    1992-04-01

    It is proved that each of two well-known fixed point iteration methods (the Mann and the Ishikawa iteration methods) converges strongly to the fixed point of strictly hemi-contractive map in real Banach spaces with property (U, λ, m+1,m), λ is an element of R, m is an element of IN. The class of strictly hemi-contractive maps includes all strictly pseudo-contractive maps with nonempty fixed point sets; and Banach spaces with property (U, λ, m+1, m), λ is an element of R, m is an element of IN include the L p (or l p ) spaces, p≥2. Our theorems generalize important known results. (author). 22 refs

  19. Computational Analysis of Host–Pathogen Protein Interactions between Humans and Different Strains of Enterohemorrhagic Escherichia coli

    Science.gov (United States)

    Bose, Tungadri; Venkatesh, K. V.; Mande, Sharmila S.

    2017-01-01

    Serotype O157:H7, an enterohemorrhagic Escherichia coli (EHEC), is known to cause gastrointestinal and systemic illnesses ranging from diarrhea and hemorrhagic colitis to potentially fatal hemolytic uremic syndrome. Specific genetic factors like ompA, nsrR, and LEE genes are known to play roles in EHEC pathogenesis. However, these factors are not specific to EHEC and their presence in several non-pathogenic strains indicates that additional factors are involved in pathogenicity. We propose a comprehensive effort to screen for such potential genetic elements, through investigation of biomolecular interactions between E. coli and their host. In this work, an in silico investigation of the protein–protein interactions (PPIs) between human cells and four EHEC strains (viz., EDL933, Sakai, EC4115, and TW14359) was performed in order to understand the virulence and host-colonization strategies of these strains. Potential host–pathogen interactions (HPIs) between human cells and the “non-pathogenic” E. coli strain MG1655 were also probed to evaluate whether and how the variations in the genomes could translate into altered virulence and host-colonization capabilities of the studied bacterial strains. Results indicate that a small subset of HPIs are unique to the studied pathogens and can be implicated in virulence. This subset of interactions involved E. coli proteins like YhdW, ChuT, EivG, and HlyA. These proteins have previously been reported to be involved in bacterial virulence. In addition, clear differences in lineage and clade-specific HPI profiles could be identified. Furthermore, available gene expression profiles of the HPI-proteins were utilized to estimate the proportion of proteins which may be involved in interactions. We hypothesized that a cumulative score of the ratios of bound:unbound proteins (involved in HPIs) would indicate the extent of colonization. Thus, we designed the Host Colonization Index (HCI) measure to determine the host

  20. Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus.

    Science.gov (United States)

    Sobel Leonard, Ashley; Weissman, Daniel B; Greenbaum, Benjamin; Ghedin, Elodie; Koelle, Katia

    2017-07-15

    advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens. Copyright © 2017 Sobel Leonard et al.

  1. Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

    Science.gov (United States)

    2016-01-01

    A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes. PMID:28090211

  2. Identification of human pathogens isolated from blood using microarray hybridisation and signal pattern recognition

    Directory of Open Access Journals (Sweden)

    Presterl Elisabeth

    2007-08-01

    Full Text Available Abstract Background Pathogen identification in clinical routine is based on the cultivation of microbes with subsequent morphological and physiological characterisation lasting at least 24 hours. However, early and accurate identification is a crucial requisite for fast and optimally targeted antimicrobial treatment. Molecular biology based techniques allow fast identification, however discrimination of very closely related species remains still difficult. Results A molecular approach is presented for the rapid identification of pathogens combining PCR amplification with microarray detection. The DNA chip comprises oligonucleotide capture probes for 25 different pathogens including Gram positive cocci, the most frequently encountered genera of Enterobacteriaceae, non-fermenter and clinical relevant Candida species. The observed detection limits varied from 10 cells (e.g. E. coli to 105 cells (S. aureus per mL artificially spiked blood. Thus the current low sensitivity for some species still represents a barrier for clinical application. Successful discrimination of closely related species was achieved by a signal pattern recognition approach based on the k-nearest-neighbour method. A prototype software providing this statistical evaluation was developed, allowing correct identification in 100 % of the cases at the genus and in 96.7 % at the species level (n = 241. Conclusion The newly developed molecular assay can be carried out within 6 hours in a research laboratory from pathogen isolation to species identification. From our results we conclude that DNA microarrays can be a useful tool for rapid identification of closely related pathogens particularly when the protocols are adapted to the special clinical scenarios.

  3. Physicochemical Factors Influence the Abundance and Culturability of Human Enteric Pathogens and Fecal Indicator Organisms in Estuarine Water and Sediment

    Directory of Open Access Journals (Sweden)

    Francis Hassard

    2017-10-01

    Full Text Available To assess fecal pollution in coastal waters, current monitoring is reliant on culture-based enumeration of bacterial indicators, which does not account for the presence of viable but non-culturable or sediment-associated micro-organisms, preventing effective quantitative microbial risk assessment (QMRA. Seasonal variability in viable but non-culturable or sediment-associated bacteria challenge the use of fecal indicator organisms (FIOs for water monitoring. We evaluated seasonal changes in FIOs and human enteric pathogen abundance in water and sediments from the Ribble and Conwy estuaries in the UK. Sediments possessed greater bacterial abundance than the overlying water column, however, key pathogenic species (Shigella spp., Campylobacter jejuni, Salmonella spp., hepatitis A virus, hepatitis E virus and norovirus GI and GII were not detected in sediments. Salmonella was detected in low levels in the Conwy water in spring/summer and norovirus GII was detected in the Ribble water in winter. The abundance of E. coli and Enterococcus spp. quantified by culture-based methods, rarely matched the abundance of these species when measured by qPCR. The discrepancy between these methods was greatest in winter at both estuaries, due to low CFU's, coupled with higher gene copies (GC. Temperature accounted for 60% the variability in bacterial abundance in water in autumn, whilst in winter salinity explained 15% of the variance. Relationships between bacterial indicators/pathogens and physicochemical variables were inconsistent in sediments, no single indicator adequately described occurrence of all bacterial indicators/pathogens. However, important variables included grain size, porosity, clay content and concentrations of Zn, K, and Al. Sediments with greater organic matter content and lower porosity harbored a greater proportion of non-culturable bacteria (including dead cells and extracellular DNA in winter. Here, we show the link between physicochemical

  4. Role of Human Action in the Spread of Honey Bee (Hymenoptera: Apidae) Pathogens.

    Science.gov (United States)

    Owen, Robert

    2017-06-01

    The increased annual losses in European honey bee (Apis mellifera) colonies in North America and some other countries is usually attributed to a range of factors including pathogens, poor nutrition, and insecticides. In this essay, I will argue that the global trade in honey bees and migratory beekeeping practices within countries has enabled pathogens to spread quickly. Beekeepers' management strategies have also contributed to the spread of pathogens as well as the development of resistance to miticides and antibiotics, and exacerbated by hobby beekeepers. The opportunities for arresting honey bee declines rest as strongly with individual beekeepers as they do with the dynamics of disease. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Paramecium species ingest and kill the cells of the human pathogenic fungus Cryptococcus neoformans.

    Science.gov (United States)

    Frager, Shalom Z; Chrisman, Cara J; Shakked, Rachel; Casadevall, Arturo

    2010-08-01

    A fundamental question in the field of medical mycology is the origin of virulence in those fungal pathogens acquired directly from the environment. In recent years, it was proposed that the virulence of certain environmental animal-pathogenic microbes, such as Cryptococcus neoformans, originated from selection pressures caused by species-specific predation. In this study, we analyzed the interaction of C. neoformans with three Paramecium spp., all of which are ciliated mobile protists. In contrast to the interaction with amoebae, some Paramecium spp. rapidly ingested C. neoformans and killed the fungus. This study establishes yet another type of protist-fungal interaction supporting the notion that animal-pathogenic fungi in the environment are under constant selection by predation.

  6. ISHAM-ITS reference DNA barcoding database - the quality controlled standard tool for routine identification of human and animal pathogenic fungi

    NARCIS (Netherlands)

    Robert, Vincent

    2015-01-01

    Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and

  7. A Rapid and Simple Real-Time PCR Assay for Detecting Foodborne Pathogenic Bacteria in Human Feces.

    Science.gov (United States)

    Hanabara, Yutaro; Ueda, Yutaka

    2016-11-22

    A rapid, simple method for detecting foodborne pathogenic bacteria in human feces is greatly needed. Here, we examined the efficacy of a method that employs a combination of a commercial PCR master mix, which is insensitive to PCR inhibitors, and a DNA extraction method which used sodium dodecyl benzene sulfonate (SDBS), and Tween 20 to counteract the inhibitory effects of SDBS on the PCR assay. This method could detect the target genes (stx1 and stx2 of enterohemorrhagic Escherichia coli, invA of Salmonella Enteritidis, tdh of Vibrio parahaemolyticus, gyrA of Campylobacter jejuni, ceuE of Campylobacter coli, SEA of Staphylococcus aureus, ces of Bacillus cereus, and cpe of Clostridium perfringens) in a fecal suspension containing 1.0 × 10 1 to 1.0 × 10 3 CFU/ml. Furthermore, the assay was neither inhibited nor influenced by individual differences among the fecal samples of 10 subjects or fecal concentration (40-160 mg/ml in the fecal suspension). When we attempted to detect the genes of pathogenic bacteria in 4 actual clinical cases, we found that this method was more sensitive than standard culture method. These results showed that this assay is a rapid, simple detection method for foodborne pathogenic bacteria in human feces.

  8. Characterization of the interaction between the human pathogen Listeria monocytogenes and the model host C. elegans

    DEFF Research Database (Denmark)

    Simonsen, Karina T.; Nielsen, Jesper S.; Hansen, Annie A.

    . In addition, C. elegans is a promising model for the identification of novel virulence factors in various pathogens. A large number of human, animal, plant and insect pathogens have been shown to kill the worm, when C. elegans was allowed to feed on pathogens in stead of its normal laboratory diet [1....... elegans. Finally, we have developed a liquid based killing assay which enables us to set up a high-throughput screening system for the identification of L. monocytogenes virulence genes required for host-pathogen interactions.     References:   [1]: Kurz, C. L., and Ewbank, J. J. (2007) Curr Opin...

  9. Mann iteration with errors for strictly pseudo-contractive mappings ...

    African Journals Online (AJOL)

    It is well known that any fixed point of a Lipschitzian strictly pseudo-contractive self mapping of a nonempty closed convex and bounded subset K of a Banach space X is unique [6] and may be norm approximated by an iterative procedure. In this paper, we show that Mann iteration with errors can be used to approximate the ...

  10. Dominated operators, absolutely summing operators and the strict ...

    African Journals Online (AJOL)

    b(X;E) be the space of all E-valued bounded continuous functions on X, equipped with the strict topology β. We study dominated and absolutely summing operators T : Cb(X;E) → F. We derive that if X is a locally compact Hausdorff space and E ...

  11. Convergence of GAOR Iterative Method with Strictly Diagonally Dominant Matrices

    Directory of Open Access Journals (Sweden)

    Guangbin Wang

    2011-01-01

    Full Text Available We discuss the convergence of GAOR method for linear systems with strictly diagonally dominant matrices. Moreover, we show that our results are better than ones of Darvishi and Hessari (2006, Tian et al. (2008 by using three numerical examples.

  12. Runaway selection for cooperation and strict-and-severe punishment.

    Science.gov (United States)

    Nakamaru, Mayuko; Dieckmann, Ulf

    2009-03-07

    Punishing defectors is an important means of stabilizing cooperation. When levels of cooperation and punishment are continuous, individuals must employ suitable social standards for defining defectors and for determining punishment levels. Here we investigate the evolution of a social reaction norm, or psychological response function, for determining the punishment level meted out by individuals in dependence on the cooperation level exhibited by their neighbors in a lattice-structured population. We find that (1) cooperation and punishment can undergo runaway selection, with evolution towards enhanced cooperation and an ever more demanding punishment reaction norm mutually reinforcing each other; (2) this mechanism works best when punishment is strict, so that ambiguities in defining defectors are small; (3) when the strictness of punishment can adapt jointly with the threshold and severity of punishment, evolution favors the strict-and-severe punishment of individuals who offer slightly less than average cooperation levels; (4) strict-and-severe punishment naturally evolves and leads to much enhanced cooperation when cooperation without punishment would be weak and neither cooperation nor punishment are too costly; and (5) such evolutionary dynamics enable the bootstrapping of cooperation and punishment, through which defectors who never punish gradually and steadily evolve into cooperators who punish those they define as defectors.

  13. Dominance on Strict Triangular Norms and Mulholland Inequality

    Czech Academy of Sciences Publication Activity Database

    Petrík, Milan

    2018-01-01

    Roč. 335, 15 March (2018), s. 3-17 ISSN 0165-0114 R&D Projects: GA ČR GJ15-07724Y Institutional support: RVO:67985807 Keywords : dominance relation * Mulholland inequality * strict triangular norm * transitivity Subject RIV: BA - General Mathematics Impact factor: 2.718, year: 2016

  14. Sporothrix schenckii (sensu strict S. globosa) mating type 1-2 (MAT1-2) gene.

    Science.gov (United States)

    Kano, Rui; Anzawa, Kazushi; Mochizuki, Takashi; Nishimoto, Katsutaro; Hiruma, Masataro; Kamata, Hiroshi; Hasegawa, Atsuhiko

    2013-09-01

    Sporotix schenckii is a pathogenic fungus that causes human and animal sporotrichosis, and based on morphology of the sessile conidia and molecular analysis, it was recently recognized as a species complex comprising at least the following six sibling species: S. albicans, S. brasiliensis, S. globosa, S. luriei, S. mexicana and S. schenckii. However, apart from S. schenckii sensu strict, only S. brasiliensis, S. globosa and S. luriei are associated with human and animal infection. S. globosa has been most commonly isolated in Asia, Europe and the USA; therefore, molecular epidemiological study for S. globosa is important in relation to human sporotrichosis in Japan. To the best of our knowledge, this is the first study to determine the mating type 1-2 (MAT1-2) gene of Sporothrix schenckii with the aim of understanding the taxonomy of the genus Sporothrix. The MAT1-2 gene (1618 bp) encodes a protein sequence of 198 amino acids. Reverse transcription polymerase chain reaction analysis also detected MAT1-2 gene mRNA expression in all of the S. schenckii strains examined, indicating that this gene is expressed in S. schenckii cells. Phylogenetic analysis of the MAT1-2 gene fragments of Ophiostoma himal-ulmi, O. novo-ulmi, O. ulmi and S. schenckii indicated that these isolates could be classified into four clusters. MAT1-1 gene-specific polymerase chain reaction was positive in 15 isolates, but negative in four human isolates and one feline isolate. © 2013 Japanese Dermatological Association.

  15. Bioelectronic DNA detection of human papillomaviruses using eSensor™: a model system for detection of multiple pathogens

    Directory of Open Access Journals (Sweden)

    Miller Donna L

    2003-06-01

    Full Text Available Abstract Background We used human papillomaviruses (HPV as a model system to evaluate the utility of a nucleic acid, hybridization-based bioelectronic DNA detection platform (eSensor™ in identifying multiple pathogens. Methods Two chips were spotted with capture probes consisting of DNA oligonucleotide sequences specific for HPV types. Electrically conductive signal probes were synthesized to be complementary to a distinct region of the amplified HPV target DNA. A portion of the HPV L1 region that was amplified by using consensus primers served as target DNA. The amplified target was mixed with a cocktail of signal probes and added to a cartridge containing a DNA chip to allow for hybridization with complementary capture probes. Results Two bioelectric chips were designed and successfully detected 86% of the HPV types contained in clinical samples. Conclusions This model system demonstrates the potential of the eSensor platform for rapid and integrated detection of multiple pathogens.

  16. Motor coordination and balance measurements reveal differential pathogenicity of currently spreading enterovirus 71 strains in human SCARB2 transgenic mice.

    Science.gov (United States)

    Chen, Mei-Feng; Shih, Shin-Ru

    2016-12-01

    Enterovirus 71 (EV71) has caused large-scale epidemics with neurological complications in the Asia-Pacific region. The C4a and B5 strains are the two major genotypes circulating in many countries recently. This study used a new protocol, a motor coordination task, to assess the differential pathogenicity of C4a and B5 strains in human SCARB2 transgenic mice. We found that the pathogenicity of C4a viruses was more severe than that of B5 viruses. Moreover, we discovered that an increased level of monocyte chemoattractant protein-1 was positively correlated with severely deficient motor function. This study provides a new method for evaluating EV71 infection in mice and distinguishing the severity of the symptoms caused by different clinical strains, which would contribute to studies of pathogenesis and development of vaccines and antivirals in EV71 infections.

  17. In Silico Prediction of Human Pathogenicity in the gamma-Proteobacteria

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Nielsen, Morten; Aarestrup, Frank Møller

    2010-01-01

    of features that appear to correlate with virulence. The method does not rely on identifying genes known to be involved in pathogenicity (for instance virulence factors), but rather it inherently builds families of proteins that, irrespective of their function, are consistently present in only one of the two...

  18. Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1

    NARCIS (Netherlands)

    Koning, Nathalie; Kessen, Sabine F M; Van Der Voorn, J Patrick; Appelmelk, Ben J; Jeurink, Prescilla V; Knippels, Leon M J; Garssen, Johan; Van Kooyk, Yvette

    2015-01-01

    Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA

  19. Development of real-time PCR array for simultaneous detection of eight human blood-borne viral pathogens.

    Directory of Open Access Journals (Sweden)

    Natalia Pripuzova

    Full Text Available BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2, hepatitis B virus (HBV, hepatitis C virus (HCV, human T-cell leukemia virus-1 and -2 (HTLV-1 and -2, vaccinia virus (VACV and West Nile virus (WNV. One hundred twenty (120 primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B, HBV (genotype A and WNV. It detected 100-1,000 geq/ml of plasma of HIV-1 subtypes (A - G, group N and CRF (AE and AG isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors' clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.

  20. Structure of the sliding clamp from the fungal pathogen Aspergillus fumigatus (AfumPCNA) and interactions with Human p21.

    Science.gov (United States)

    Marshall, Andrew C; Kroker, Alice J; Murray, Lauren A M; Gronthos, Kahlia; Rajapaksha, Harinda; Wegener, Kate L; Bruning, John B

    2017-03-01

    The fungal pathogen Aspergillus fumigatus has been implicated in a drastic increase in life-threatening infections over the past decade. However, compared to other microbial pathogens, little is known about the essential molecular processes of this organism. One such fundamental process is DNA replication. The protein responsible for ensuring processive DNA replication is PCNA (proliferating cell nuclear antigen, also known as the sliding clamp), which clamps the replicative polymerase to DNA. Here we present the first crystal structure of a sliding clamp from a pathogenic fungus (A. fumigatus), at 2.6Å. Surprisingly, the structure bears more similarity to the human sliding clamp than other available fungal sliding clamps. Reflecting this, fluorescence polarization experiments demonstrated that AfumPCNA interacts with the PCNA-interacting protein (PIP-box) motif of human p21 with an affinity (K d ) of 3.1 μm. Molecular dynamics simulations were carried out to better understand how AfumPCNA interacts with human p21. These simulations revealed that the PIP-box bound to AfuPCNA forms a secondary structure similar to that observed in the human complex, with a central 3 10 helix contacting the hydrophobic surface pocket of AfumPCNA as well as a β-strand that forms an antiparallel sheet with the AfumPCNA surface. Differences in the 3 10 helix interaction with PCNA, attributed to residue Thr131 of AfumPCNA, and a less stable β-strand formation, attributed to residues Gln123 and His125 of AfumPCNA, are likely causes of the over 10-fold lower affinity of the p21 PIP-box for AfumPCNA as compared to hPCNA. The atomic coordinates and structure factors for the Aspergillus fumigatus sliding clamp can be found in the RCSB Protein Data Bank (http://www.rcsb.org) under the accession code 5TUP. © 2017 Federation of European Biochemical Societies.

  1. The construction and evaluation of reference spectra for the identification of human pathogenic microorganisms by MALDI-TOF MS.

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    Di Xiao

    Full Text Available Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS is an emerging technique for the rapid and high-throughput identification of microorganisms. There remains a dearth of studies in which a large number of pathogenic microorganisms from a particular country or region are utilized for systematic analyses. In this study, peptide mass reference spectra (PMRS were constructed and evaluated from numerous human pathogens (a total of 1019 strains from 94 species, including enteric (46 species, respiratory (21 species, zoonotic (17 species, and nosocomial pathogens (10 species, using a MALDI-TOF MS Biotyper system (MBS. The PMRS for 380 strains of 52 species were new contributions to the original reference database (ORD. Compared with the ORD, the new reference database (NRD allowed for 28.2% (from 71.5% to 99.7% and 42.3% (from 51.3% to 93.6% improvements in identification at the genus and species levels, respectively. Misidentification rates were 91.7% and 57.1% lower with the NRD than with the ORD for genus and species identification, respectively. Eight genera and 25 species were misidentified. For genera and species that are challenging to accurately identify, identification results must be manually determined and adjusted in accordance with the database parameters. Through augmentation, the MBS demonstrated a high identification accuracy and specificity for human pathogenic microorganisms. This study sought to provide theoretical guidance for using PMRS databases in various fields, such as clinical diagnosis and treatment, disease control, quality assurance, and food safety inspection.

  2. In vitro screening of mucus and solvent extracts of Eisenia foetida against human bacterial and fungal pathogens.

    Science.gov (United States)

    Andleeb, Saiqa; Ejaz, Mubashir; Awan, Uzma Azeem; Ali, Shaukat; Kiyani, Ayesha; Shafique, Irsa; Zafar, Atiya

    2016-05-01

    Earthworms are macro invertebrate and have been widely used as therapeutic drugs for thousands of years. In the current research, experiments viz., the antibacterial, antifungal and antioxidant activity of mucus and solvent extracts of Eisenia foetida were conducted to investigate for the first time in Pakistan against human infectious pathogens. Antimicrobial activity of E. foetida against human pathogens underwent investigation through an agar disc diffusion method while an ABTS(•+) free radical scavenging method assessed the antioxidant activity. The percentage of bacterial and fungal growth was analyzed statistically with One-Way Analysis of Variance (ANOVA). Results showed that the mucus IV of E. foetida produced a strong potent antibacterial and antifungal activity. Pseudomonas aeruginosa exhibited the highest inhibition zone (33.67±1.53 mm), followed by Klebsiella pneumonia (30.33±1.53mm), Penicillium notatum (30±0.051), Escherichia coli (29±1 mm), Candida albicans (28.33±0.54 mm), Staphylococcus aureus (27±1mm), Serratia marcescens (25.33±0.58 mm), Aspergillus flavus (25.33±0.58 mm), Staphylococcus epidermidis (24.33±0.58 mm), Streptococcus pyogenes (21.67±1.53 mm), and Aspergillus niger (20.67±0.53 mm). Mucus IV of E. foetida also showed the highest antioxidant activity (99%). The results clearly indicate that the mucus and solvent extracts contain effective antimicrobial properties and bioactive compounds to inhibit the growth of infectious pathogens. We conclude that mucus extracts of earthworm have significant level of antimicrobial and antioxidant activities and in future could be potentially used against various infectious pathogens.

  3. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

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    Dolores L. Guzmán-Herrador

    2017-08-01

    Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  4. Risk of Human Infections With Highly Pathogenic H5N2 and Low Pathogenic H7N1 Avian Influenza Strains During Outbreaks in Ostriches in South Africa.

    Science.gov (United States)

    Venter, Marietjie; Treurnicht, Florette K; Buys, Amelia; Tempia, Stefano; Samudzi, Rudo; McAnerney, Johanna; Jacobs, Charlene A; Thomas, Juno; Blumberg, Lucille

    2017-09-15

    Risk factors for human infection with highly pathogenic (HP) and low-pathogenic (LP) avian influenza (AI) H5N2 and H7N1 were investigated during outbreaks in ostriches in the Western Cape province, South Africa. Serum surveys were conducted for veterinarians, farmworkers, and laboratory and abattoir workers involved in 2 AI outbreaks in the Western Cape province: (1) controlling and culling of 42000 ostriches during (HPAI)H5N2 outbreaks in ostriches (2011) (n = 207); (2) movement control during (LPAI)H7N1 outbreaks in 2012 (n = 66). A third serosurvey was conducted on state veterinarians from across the country in 2012 tasked with disease control in general (n = 37). Antibodies to H5 and H7 were measured by means of hemagglutination inhibition and microneutralization assays, with microneutralization assay titers >40 considered positive. Two of 207 (1%) participants were seropositive for H5 and 4 of 207 (2%) for H7 in 2011, compared with 1 of 66 (1.5%) and 8 of 66 (13%) in 2012. Although individuals in all professions tested seropositive, abattoir workers (10 of 97; 10.3%) were significantly more at risk of influenza A(H7N1) infection (P = .001) than those in other professions (2 of 171;1.2%). Among state veterinarians, 4 of 37(11%) were seropositive for H7 and 1 of 37 (2.7%) for H5. Investigations of (LP)H7N1-associated fatalities in wild birds and quarantined exotic birds in Gauteng, AI outbreaks in poultry in KwaZulu-Natal, and ostriches in Western Cape province provide possible exposure events. (LPAI)H7N1 strains pose a greater infection-risk than (HPAI)H5N2 strains to persons involved in control of outbreaks in infected birds, with ostrich abattoir workers at highest risk. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  5. Human ecology in pathogenic landscapes: two hypotheses on how land use change drives viral emergence

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    Murray, Kris. A.; Daszak, Peter

    2013-01-01

    The emergence of novel viral diseases is driven by socioeconomic, demographic and environmental changes. These include land use changes such as deforestation, agricultural expansion and habitat degradation. However, the links between land use change and disease emergence are poorly understood and likely complex. In this review, we propose two hypotheses for the mechanisms by which land use change can lead to viral emergence: 1) by perturbing disease dynamics in multi-host disease systems via impacts on cross-species transmission rates (the ‘perturbation’ hypothesis); and 2) by allowing exposure of novel hosts to a rich pool of pathogen diversity (the ‘pathogen pool’ hypothesis). We discuss ways that these two hypotheses might be tested using a combination of ecological and virological approaches, and how this may provide novel control and prevention strategies. PMID:23415415

  6. Isolate-dependent growth, virulence, and cell wall composition in the human pathogen Aspergillus fumigatus.

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    Nansalmaa Amarsaikhan

    Full Text Available The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.

  7. Candida and Fusarium species known as opportunistic human pathogens from customer-accessible parts of residential washing machines.

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    Babič, Monika Novak; Zalar, Polona; Ženko, Bernard; Schroers, Hans-Josef; Džeroski, Sašo; Gunde-Cimerman, Nina

    2015-03-01

    Energy constraints have altered consumer practice regarding the use of household washing machines. Washing machines were developed that use lower washing temperatures, smaller amounts of water and biodegradable detergents. These conditions may favour the enrichment of opportunistic human pathogenic fungi. We focused on the isolation of fungi from two user-accessible parts of washing machines that often contain microbial biofilms: drawers for detergents and rubber door seals. Out of 70 residential washing machines sampled in Slovenia, 79% were positive for fungi. In total, 72 strains belonging to 12 genera and 26 species were isolated. Among these, members of the Fusarium oxysporum and Fusarium solani species complexes, Candida parapsilosis and Exophiala phaeomuriformis represented 44% of fungi detected. These species are known as opportunistic human pathogens and can cause skin, nail or eye infections also in healthy humans. A machine learning analysis revealed that presence of detergents and softeners followed by washing temperature, represent most critical factors for fungal colonization. Three washing machines with persisting malodour that resulted in bad smelling laundry were analysed for the presence of fungi and bacteria. In these cases, fungi were isolated in low numbers (7.5 %), while bacteria Micrococcus luteus, Pseudomonas aeruginosa, and Sphingomonas species prevailed. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  8. The streamlined genome of Phytomonas spp. relative to human pathogenic kinetoplastids reveals a parasite tailored for plants.

    Science.gov (United States)

    Porcel, Betina M; Denoeud, France; Opperdoes, Fred; Noel, Benjamin; Madoui, Mohammed-Amine; Hammarton, Tansy C; Field, Mark C; Da Silva, Corinne; Couloux, Arnaud; Poulain, Julie; Katinka, Michael; Jabbari, Kamel; Aury, Jean-Marc; Campbell, David A; Cintron, Roxana; Dickens, Nicholas J; Docampo, Roberto; Sturm, Nancy R; Koumandou, V Lila; Fabre, Sandrine; Flegontov, Pavel; Lukeš, Julius; Michaeli, Shulamit; Mottram, Jeremy C; Szöőr, Balázs; Zilberstein, Dan; Bringaud, Frédéric; Wincker, Patrick; Dollet, Michel

    2014-02-01

    Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease.

  9. Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen Burkholderia pseudomallei K96243.

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    Andrea J Dowling

    2010-12-01

    Full Text Available Burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. The bacterium is endemic to tropical regions, including South East Asia and Northern Australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages. However despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterized to date. Here we perform a genome-wide gain of function screen of B. pseudomallei strain K96243 to identify loci encoding factors with anti-macrophage activity. We identify a total of 113 such loci scattered across both chromosomes, with positive gene clusters encoding transporters and secretion systems, enzymes/toxins, secondary metabolite, biofilm, adhesion and signal response related factors. Further phenotypic analysis of four of these regions shows that the encoded factors cause striking cellular phenotypes relevant to infection biology, including apoptosis, formation of actin 'tails' and multi-nucleation within treated macrophages. The detailed analysis of the remaining host of loci will facilitate genetic dissection of the interaction of this important pathogen with host macrophages and thus further elucidate this critical part of its infection cycle.

  10. The Streamlined Genome of Phytomonas spp. Relative to Human Pathogenic Kinetoplastids Reveals a Parasite Tailored for Plants

    Science.gov (United States)

    Porcel, Betina M.; Denoeud, France; Opperdoes, Fred; Noel, Benjamin; Madoui, Mohammed-Amine; Hammarton, Tansy C.; Field, Mark C.; Da Silva, Corinne; Couloux, Arnaud; Poulain, Julie; Katinka, Michael; Jabbari, Kamel; Aury, Jean-Marc; Campbell, David A.; Cintron, Roxana; Dickens, Nicholas J.; Docampo, Roberto; Sturm, Nancy R.; Koumandou, V. Lila; Fabre, Sandrine; Flegontov, Pavel; Lukeš, Julius; Michaeli, Shulamit; Mottram, Jeremy C.; Szöőr, Balázs; Zilberstein, Dan; Bringaud, Frédéric; Wincker, Patrick; Dollet, Michel

    2014-01-01

    Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease. PMID:24516393

  11. Construction of a highly flexible and comprehensive gene collection representing the ORFeome of the human pathogen Chlamydia pneumoniae

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    Maier Christina J

    2012-11-01

    Full Text Available Abstract Background The Gram-negative bacterium Chlamydia pneumoniae (Cpn is the leading intracellular human pathogen responsible for respiratory infections such as pneumonia and bronchitis. Basic and applied research in pathogen biology, especially the elaboration of new mechanism-based anti-pathogen strategies, target discovery and drug development, rely heavily on the availability of the entire set of pathogen open reading frames, the ORFeome. The ORFeome of Cpn will enable genome- and proteome-wide systematic analysis of Cpn, which will improve our understanding of the molecular networks and mechanisms underlying and governing its pathogenesis. Results Here we report the construction of a comprehensive gene collection covering 98.5% of the 1052 predicted and verified ORFs of Cpn (Chlamydia pneumoniae strain CWL029 in Gateway® ‘entry’ vectors. Based on genomic DNA isolated from the vascular chlamydial strain CV-6, we constructed an ORFeome library that contains 869 unique Gateway® entry clones (83% coverage and an additional 168 PCR-verified ‘pooled’ entry clones, reaching an overall coverage of ~98.5% of the predicted CWL029 ORFs. The high quality of the ORFeome library was verified by PCR-gel electrophoresis and DNA sequencing, and its functionality was demonstrated by expressing panels of recombinant proteins in Escherichia coli and by genome-wide protein interaction analysis for a test set of three Cpn virulence factors in a yeast 2-hybrid system. The ORFeome is available in different configurations of resource stocks, PCR-products, purified plasmid DNA, and living cultures of E. coli harboring the desired entry clone or pooled entry clones. All resources are available in 96-well microtiterplates. Conclusion This first ORFeome library for Cpn provides an essential new tool for this important pathogen. The high coverage of entry clones will enable a systems biology approach for Cpn or host–pathogen analysis. The high yield of

  12. An image classification approach to analyze the suppression of plant immunity by the human pathogen Salmonella Typhimurium

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    Schikora Marek

    2012-07-01

    Full Text Available Abstract Background The enteric pathogen Salmonella is the causative agent of the majority of food-borne bacterial poisonings. Resent research revealed that colonization of plants by Salmonella is an active infection process. Salmonella changes the metabolism and adjust the plant host by suppressing the defense mechanisms. In this report we developed an automatic algorithm to quantify the symptoms caused by Salmonella infection on Arabidopsis. Results The algorithm is designed to attribute image pixels into one of the two classes: healthy and unhealthy. The task is solved in three steps. First, we perform segmentation to divide the image into foreground and background. In the second step, a support vector machine (SVM is applied to predict the class of each pixel belonging to the foreground. And finally, we do refinement by a neighborhood-check in order to omit all falsely classified pixels from the second step. The developed algorithm was tested on infection with the non-pathogenic E. coli and the plant pathogen Pseudomonas syringae and used to study the interaction between plants and Salmonella wild type and T3SS mutants. We proved that T3SS mutants of Salmonella are unable to suppress the plant defenses. Results obtained through the automatic analyses were further verified on biochemical and transcriptome levels. Conclusion This report presents an automatic pixel-based classification method for detecting “unhealthy” regions in leaf images. The proposed method was compared to existing method and showed a higher accuracy. We used this algorithm to study the impact of the human pathogenic bacterium Salmonella Typhimurium on plants immune system. The comparison between wild type bacteria and T3SS mutants showed similarity in the infection process in animals and in plants. Plant epidemiology is only one possible application of the proposed algorithm, it can be easily extended to other detection tasks, which also rely on color information, or

  13. An image classification approach to analyze the suppression of plant immunity by the human pathogen Salmonella Typhimurium.

    Science.gov (United States)

    Schikora, Marek; Neupane, Balram; Madhogaria, Satish; Koch, Wolfgang; Cremers, Daniel; Hirt, Heribert; Kogel, Karl-Heinz; Schikora, Adam

    2012-07-19

    The enteric pathogen Salmonella is the causative agent of the majority of food-borne bacterial poisonings. Resent research revealed that colonization of plants by Salmonella is an active infection process. Salmonella changes the metabolism and adjust the plant host by suppressing the defense mechanisms. In this report we developed an automatic algorithm to quantify the symptoms caused by Salmonella infection on Arabidopsis. The algorithm is designed to attribute image pixels into one of the two classes: healthy and unhealthy. The task is solved in three steps. First, we perform segmentation to divide the image into foreground and background. In the second step, a support vector machine (SVM) is applied to predict the class of each pixel belonging to the foreground. And finally, we do refinement by a neighborhood-check in order to omit all falsely classified pixels from the second step. The developed algorithm was tested on infection with the non-pathogenic E. coli and the plant pathogen Pseudomonas syringae and used to study the interaction between plants and Salmonella wild type and T3SS mutants. We proved that T3SS mutants of Salmonella are unable to suppress the plant defenses. Results obtained through the automatic analyses were further verified on biochemical and transcriptome levels. This report presents an automatic pixel-based classification method for detecting "unhealthy" regions in leaf images. The proposed method was compared to existing method and showed a higher accuracy. We used this algorithm to study the impact of the human pathogenic bacterium Salmonella Typhimurium on plants immune system. The comparison between wild type bacteria and T3SS mutants showed similarity in the infection process in animals and in plants. Plant epidemiology is only one possible application of the proposed algorithm, it can be easily extended to other detection tasks, which also rely on color information, or even extended to other features.

  14. Long-Term Live Cell Imaging of Cell Migration: Effects of Pathogenic Fungi on Human Epithelial Cell Migration.

    Science.gov (United States)

    Wöllert, Torsten; Langford, George M

    2016-01-01

    Long-term live cell imaging was used in this study to determine the responses of human epithelial cells to pathogenic biofilms formed by Candida albicans. Epithelial cells of the skin represent the front line of defense against invasive pathogens such as C. albicans but under certain circumstances, especially when the host's immune system is compromised, the skin barrier is breached. The mechanisms by which the fungal pathogen penetrates the skin and invade the deeper layers are not fully understood. In this study we used keratinocytes grown in culture as an in vitro model system to determine changes in host cell migration and the actin cytoskeleton in response to virulence factors produced by biofilms of pathogenic C. albicans. It is clear that changes in epithelial cell migration are part of the response to virulence factors secreted by biofilms of C. albicans and the actin cytoskeleton is the downstream effector that mediates cell migration. Our goal is to understand the mechanism by which virulence factors hijack the signaling pathways of the actin cytoskeleton to alter cell migration and thereby invade host tissues. To understand the dynamic changes of the actin cytoskeleton during infection, we used long-term live cell imaging to obtain spatial and temporal information of actin filament dynamics and to identify signal transduction pathways that regulate the actin cytoskeleton and its associated proteins. Long-term live cell imaging was achieved using a high resolution, multi-mode epifluorescence microscope equipped with specialized light sources, high-speed cameras with high sensitivity detectors, and specific biocompatible fluorescent markers. In addition to the multi-mode epifluorescence microscope, a spinning disk confocal long-term live cell imaging system (Olympus CV1000) equipped with a stage incubator to create a stable in vitro environment for long-term real-time and time-lapse microscopy was used. Detailed descriptions of these two long-term live

  15. Molecular mapping of the cell wall polysaccharides of the human pathogen Streptococcus agalactiae

    Science.gov (United States)

    Beaussart, Audrey; Péchoux, Christine; Trieu-Cuot, Patrick; Hols, Pascal; Mistou, Michel-Yves; Dufrêne, Yves F.

    2014-11-01

    The surface of many bacterial pathogens is covered with polysaccharides that play important roles in mediating pathogen-host interactions. In Streptococcus agalactiae, the capsular polysaccharide (CPS) is recognized as a major virulence factor while the group B carbohydrate (GBC) is crucial for peptidoglycan biosynthesis and cell division. Despite the important roles of CPS and GBC, there is little information available on the molecular organization of these glycopolymers on the cell surface. Here, we use atomic force microscopy (AFM) and transmission electron microscopy (TEM) to analyze the nanoscale distribution of CPS and GBC in wild-type (WT) and mutant strains of S. agalactiae. TEM analyses reveal that in WT bacteria, peptidoglycan is covered with a very thin (few nm) layer of GBC (the ``pellicle'') overlaid by a 15-45 nm thick layer of CPS (the ``capsule''). AFM-based single-molecule mapping with specific antibody probes shows that CPS is exposed on WT cells, while it is hardly detected on mutant cells impaired in CPS production (ΔcpsE mutant). By contrast, both TEM and AFM show that CPS is over-expressed in mutant cells altered in GBC expression (ΔgbcO mutant), indicating that the production of the two surface glycopolymers is coordinated in WT cells. In addition, AFM topographic imaging and molecular mapping with specific lectin probes demonstrate that removal of CPS (ΔcpsE), but not of GBC (ΔgbcO), leads to the exposure of peptidoglycan, organized into 25 nm wide bands running parallel to the septum. These results indicate that CPS forms a homogeneous barrier protecting the underlying peptidoglycan from environmental exposure, while the presence of GBC does not prevent peptidoglycan detection. This work shows that single-molecule AFM, combined with high-resolution TEM, represents a powerful platform for analysing the molecular arrangement of the cell wall polymers of bacterial pathogens.

  16. Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans

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    Portaels Francoise

    2007-09-01

    Full Text Available Abstract Background Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as Mycobacterium tuberculosis. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel polymorphism among a diverse strain collection of Mycobacterium ulcerans, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs, comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within M. ulcerans, to define features of a hypothetical M. ulcerans most recent common ancestor and to confirm its origin from Mycobacterium marinum. Results M. ulcerans has evolved into five InDel haplotypes that separate into two distinct lineages: (i the "classical" lineage including the most pathogenic genotypes – those that come from Africa, Australia and South East Asia; and (ii an "ancestral" M. ulcerans lineage comprising strains from Asia (China/Japan, South America and Mexico. The ancestral lineage is genetically closer to the progenitor M. marinum in both RD composition and DNA sequence identity, whereas the classical lineage has undergone major genomic rearrangements. Conclusion Results of the InDel analysis are in complete accord with recent multi-locus sequence analysis and indicate that M. ulcerans has passed through at least two major evolutionary bottlenecks since divergence from M. marinum. The classical lineage shows more pronounced reductive evolution than the ancestral lineage, suggesting that there may be differences in the ecology between the two lineages. These findings improve the understanding of the adaptive evolution and virulence of M. ulcerans and pathogenic mycobacteria in general and will facilitate the development of new tools for improved diagnostics and molecular epidemiology.

  17. Antibiotic resistance genes and human bacterial pathogens: Co-occurrence, removal, and enrichment in municipal sewage sludge digesters.

    Science.gov (United States)

    Ju, Feng; Li, Bing; Ma, Liping; Wang, Yubo; Huang, Danping; Zhang, Tong

    2016-03-15

    Understanding which/how antibiotic resistance genes (ARGs) contribute to increased acquisition of resistance by pathogens in aquatic environments are challenges of profound significance. We explored the co-occurrence and removal versus enrichment of ARGs and human bacterial pathogens (HBPs) in municipal sewage sludge digesters. We combined metagenomic detection of a wide spectrum of 323 ARGs and 83 HBPs with a correlation-based statistical approach and charted a network of their co-occurrence relationships. The results indicate that most ARGs and a minor proportion of HBPs (mainly Collinsella aerofaciens, Streptococcus salivarius and Gordonia bronchialis) could not be removed by anaerobic digestion, revealing a biological risk of post-digestion sludge in disseminating antibiotic resistance and pathogenicity. Moreover, preferential co-occurrence patterns were evident within one ARG type (e.g., multidrug, beta-lactam, and aminoglycoside) and between two different ARG types (i.e., aminoglycoside and beta-lactam), possibly implicating co-effects of antibiotic selection pressure and co-resistance on shaping antibiotic resistome in sewage sludge. Unlike beta-lactam resistance genes, ARGs of multidrug and macrolide-lincosamide-streptogramin tended to co-occur more with HBPs. Strikingly, we presented evidence that the most straightforward biological origin of an ARG-species co-occurring event is a hosting relationship. Furthermore, a significant and robust HBP-species co-occurrence correlation provides a proper scenario for nominating HBP indicators (e.g., Bifidobacterium spp. are perfect indicators of C. aerofaciens; r = 0.92-0.99 and P-values < 0.01). Combined, this study demonstrates a creative and effective network-based metagenomic approach for exploring ARG hosts and HBP indicators and assessing ARGs acquisition by HBPs in human-impacted environments where ARGs and HBPs may co-thrive. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

    Directory of Open Access Journals (Sweden)

    Lee Na

    2011-05-01

    Full Text Available Abstract Background Helicobacter pylori (Hp, a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s of Hp infection. Results We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. Conclusions We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.

  19. Study of drinking water fungi and its pathogenic effects on human beings from district Bhimber, Azad Kashmir, Pakistan

    International Nuclear Information System (INIS)

    Hussain, T.; Ishtiaq, M.; Hussain, A.; Sultana, K.

    2011-01-01

    Pathogenic fungi of drinking water have potentially prevailing effects on human beings. Myco floral study of drinking water of district Bhimber, Azad Kashmir was conducted through systematic sampling and temporally during the year 2009. Drinking water samples were collected from selected spots and fungal spores were grown on two different culture media viz: potato dextrose agar (PDA) and nutrient agar (NA) and identified by employing Direct Plate method (DPM) and Baiting Technique (BT). A total of 4 resources of drinking water of the area were analyzed i.e., well, spring, hand pump and tap water (water supply system). Sixteen different fungal species were frequently prevailing in the analyzed samples and among these five species were predominantly found human pathogenic. The density of identified fungal species in well's water samples (WWS) was 11 spp. spring's water samples (SWS) 6 spp. hand pump water samples (HWS) 8 spp. and tap water samples (TWS) 7 spp. This differential incidence in the samples might be due to variation in geography, edaphalogy, altitude, temperature, in fungal growth substrate variance and analytical difference of sampling and analysis methods. The prevalence values of mycolfora in different samples were variable with WWS Mucor fragilis (18a - LSD), SWS Brevilegnia sp. (20a - LSD), HWS Aspergillus flavus (14a- LSD) and TWS Alternaria alternata (12a - LSD). It was noted that WWS more frequently depicted mycoflora because land/well provides best environment and nourishment for growth and reproduction of fungi. The economic importance and pathogenic toxicity of various species is also measured and documented in the article. (author)

  20. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    LENUS (Irish Health Repository)

    Sibartie, Shomik

    2009-01-01

    BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.

  1. Characterization and genome analysis of novel bacteriophages infecting the opportunistic human pathogens Klebsiella oxytoca and K. pneumoniae.

    Science.gov (United States)

    Park, Eun-Ah; Kim, You-Tae; Cho, Jae-Hyun; Ryu, Sangryeol; Lee, Ju-Hoon

    2017-04-01

    Klebsiella is a genus of well-known opportunistic human pathogens that are associated with diabetes mellitus and chronic pulmonary obstruction; however, this pathogen is often resistant to multiple drugs. To control this pathogen, two Klebsiella-infecting phages, K. oxytoca phage PKO111 and K. pneumoniae phage PKP126, were isolated from a sewage sample. Analysis of their host range revealed that they infect K. pneumoniae and K. oxytoca, suggesting host specificity for members of the genus Klebsiella. Stability tests confirmed that the phages are stable under various temperature (4 to 60 °C) and pH (3 to 11) conditions. A challenge assay showed that PKO111 and PKP126 inhibit growth of their host strains by 2 log and 4 log, respectively. Complete genome sequencing of the phages revealed that their genome sizes are quite different (168,758 bp for PKO111 and 50,934 bp for PKP126). Their genome annotation results showed that they have no human virulence-related genes, an important safety consideration. In addition, no lysogen-formation gene cluster was detected in either phage genome, suggesting that they are both virulent phages in their bacterial hosts. Based on these results, PKO111 and PKP126 may be good candidates for development of biocontrol agents against members of the genus Klebsiella for therapeutic purposes. A comparative analysis of tail-associated gene clusters of PKO111 and PKP126 revealed relatively low homology, suggesting that they might differ in the way they recognize and infect their specific hosts.

  2. Isolation and Evaluation of Marine Actinomycetes from Mangrove Forests in South of Iran against Some Human Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Farshid Kafilzadeh

    2013-04-01

    Full Text Available Background & Objectives: Recent studies have shown that aquatic actinomycetes can be a source of new biological products such as antibiotics and i n dustrial products. This study was designed to examine the aquatic actinomycetes isolated from mangrove forests in South of Iran and their antibacterial activities against some human pathogens.   Methods: In this study 115 samples were randomly taken from different places of a mangrove forests in South of Iran. Isolation was based on serial dilution of the samples and plating them on starch casein agar medium. Agar well diffusion and disc diffusion assays were used to examine the antibacterial activity of the isolated purified aquatic actinomycetes.   Results: The aquatic actinomycetes were isolated from 83 samples (70%. Of them, 66 (80 percent showed antibacterial activity and 17 (20% could not inhibit the human pathogenic bacteria. The diameter of the inhibitory zones (ZOI ranged from 4 to 11 mm and the biggest zone belonged to B acillus cereus (p≤0.05.   Conclusion: The findings showed that the various and useful aquatic actinomycetes for production of new antibiotic compounds are isolated easily from the mangrove forests in South of Iran. Considering the vast spreading of mangrove forests in South of Iran and the economic and simplicity of isolation of actinomycetes for industrial usage, these source can be an important and new place for research and industry.

  3. Human Lysozyme Peptidase Resistance Is Perturbed by the Anionic Glycolipid Biosurfactant Rhamnolipid Produced by the Opportunistic Pathogen Pseudomonas aeruginosa.

    Science.gov (United States)

    Andersen, Kell K; Vad, Brian S; Scavenius, Carsten; Enghild, Jan J; Otzen, Daniel E

    2017-01-10

    Infection by the opportunistic pathogen Pseudomonas aeruginosa (PA) is accompanied by the secretion of virulence factors such as the secondary metabolite rhamnolipid (RL) as well as an array of bacterial enzymes, including the peptidase elastase. The human immune system tries to counter this via defensive proteins such as lysozyme (HLZ). HLZ targets the bacterial cell wall but may also have other antimicrobial activities. The enzyme contains four disulfide bonds and shows high thermodynamic stability and resistance to proteolytic attack. Here we show that RL promotes HLZ degradation by several unrelated peptidases, including the PA elastase and human peptidases. This occurs although RL does not by itself denature HLZ. Nevertheless, RL binds in a sufficiently high stoichiometry (8:1 RL:HLZ) to neutralize the highly cationic surface of HLZ. The initial cleavage sites agree well with the domain boundaries of HLZ. Thus, binding of RL to native HLZ may be sufficient to allow proteolytic attack at slightly exposed sites on the protein, leading to subsequent degradation. Furthermore, biofilms of RL-producing strains of PA are protected better against high concentrations of HLZ than RL-free PA strains are. We conclude that pathogen-produced RL may weaken host defenses by facilitating degradation of key host proteins.

  4. Revisiting the reference genomes of human pathogenic Cryptosporidium species: reannotation of C. parvum Iowa and a new C. hominis reference.

    Science.gov (United States)

    Isaza, Juan P; Galván, Ana Luz; Polanco, Victor; Huang, Bernice; Matveyev, Andrey V; Serrano, Myrna G; Manque, Patricio; Buck, Gregory A; Alzate, Juan F

    2015-11-09

    Cryptosporidium parvum and C. hominis are the most relevant species of this genus for human health. Both cause a self-limiting diarrhea in immunocompetent individuals, but cause potentially life-threatening disease in the immunocompromised. Despite the importance of these pathogens, only one reference genome of each has been analyzed and published. These two reference genomes were sequenced using automated capillary sequencing; as of yet, no next generation sequencing technology has been applied to improve their assemblies and annotations. For C. hominis, the main challenge that prevents a larger number of genomes to be sequenced is its resistance to axenic culture. In the present study, we employed next generation technology to analyse the genomic DNA and RNA to generate a new reference genome sequence of a C. hominis strain isolated directly from human stool and a new genome annotation of the C. parvum Iowa reference genome.

  5. Irreversible electropermeabilization of the human pathogen Candida albicans: an in-vitro experimental study.

    Science.gov (United States)

    Novickij, Vitalij; Grainys, Audrius; Svediene, Jurgita; Markovskaja, Svetlana; Paskevicius, Algimantas; Novickij, Jurij

    2015-02-01

    Pathogenic fungi cause many life-threatening infections, especially among individuals with immune system dysfunction. The antifungal drugs commonly used to suppress fungal pathogens can result in long-lasting and toxic therapy. In this work, irreversible electropermeabilization was used to investigate the dynamics of the decrease in Candida albicans colony vitality after application of a pulsed electric field (PEF) and use of antifungal drugs. The fungi were subjected to single 250-µs to 2-ms (0.5-2.5 kV/cm) pulses or repeated short 5-µs pulses, and efficacy was compared. It was shown that electropermeabilization combined with antifungal agents results in rapid and more effective treatment, eliminating more than 90% of C. albicans colony-forming units in a single procedure, which is advantageous in biomedicine. It was also observed that, because of application of PEF and use of the antifungal agents, the Candida cells form cell aggregates and average live cell size is reduced by as much as 53%.

  6. Studies on antimicrobial and antifungal activities of ziziphus mauritiana human clinical bacterial and fungal pathogens

    International Nuclear Information System (INIS)

    Amin, A.; Shah, S.; Khan, M.A.; Khan, M.M.

    2012-01-01

    The antimicrobial and antifungal activities of crude extracts of Ziziphus mauritiana leaves were investigated against six selected bacterial (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella pneumoniae) and one fungal pathogen (Aspel-gillus niger). The crude extract was further fractionated in butanol, choloroform, n-hexane and methanol. Agar well diffusion and agar dilution assay were employed for determination of zones of inhibition and MICs, respectively, whereas MBC was determined using broth dilution test. The butanol fraction presented encouraging antimicrobial activity (15.0%0.02), while methanol (7.03:1:0.05) and chloroform (7.0%0,05) fractions emerged with significantly low susceptibility. The n-hexane fraction was recorded as almost inactive (0%0) against all bacterial pathogens. Unlike the antibacterial activities, all fractions possessed momentous antifungal activities except the methanol fraction (0%0). The n-hexane fraction showed widest zone of inhibition (11:1:0.05) followed by butanol (8.0%0.02) and chloroform (7.0%0.02). (author)

  7. Genomic library screening for viruses from the human dental plaque revealed pathogen-specific lytic phage sequences.

    Science.gov (United States)

    Al-Jarbou, Ahmed Nasser

    2012-01-01

    Bacterial pathogenesis presents an astounding arsenal of virulence factors that allow them to conquer many different niches throughout the course of infection. Principally fascinating is the fact that some bacterial species are able to induce different diseases by expression of different combinations of virulence factors. Nevertheless, studies aiming at screening for the presence of bacteriophages in humans have been limited. Such screening procedures would eventually lead to identification of phage-encoded properties that impart increased bacterial fitness and/or virulence in a particular niche, and hence, would potentially be used to reverse the course of bacterial infections. As the human oral cavity represents a rich and dynamic ecosystem for several upper respiratory tract pathogens. However, little is known about virus diversity in human dental plaque which is an important reservoir. We applied the culture-independent approach to characterize virus diversity in human dental plaque making a library from a virus DNA fraction amplified using a multiple displacement method and sequenced 80 clones. The resulting sequence showed 44% significant identities to GenBank databases by TBLASTX analysis. TBLAST homology comparisons showed that 66% was viral; 18% eukarya; 10% bacterial; 6% mobile elements. These sequences were sorted into 6 contigs and 45 single sequences in which 4 contigs and a single sequence showed significant identity to a small region of a putative prophage in the Corynebacterium diphtheria genome. These findings interestingly highlight the uniqueness of over half of the sequences, whilst the dominance of a pathogen-specific prophage sequences imply their role in virulence.

  8. Debaryomyces hansenii (Candida famata), a rare human fungal pathogen often misidentified as Pichia guilliermondii (Candida guilliermondii)

    NARCIS (Netherlands)

    Desnos-Ollivier, Marie; Ragon, Marie; Robert, Vincent; Raoux, Dorothée; Gantier, Jean-Charles; Dromer, Françoise

    2008-01-01

    Debaryomyces hansenii is a hemiascomycetous yeast commonly found in natural substrates and in various types of cheese. Pichia guilliermondii is widely distributed in nature and is a common constituent of the normal human microflora. Both species have been described in human infections but are

  9. ANIMAL PATHOGENS THAT MAY CAUSE HUMAN DISEASE THAT ORIGINATE FROM FARM OPERATIONS

    Science.gov (United States)

    The recent increase in concentrated animal feeding operations in the United States has caused renewed concern regarding the infectious diseases that may be passed from farm animals to humans via the environment. It is also known that more than 20 recent epidemics among humans cou...

  10. T cell immunity. Functional heterogeneity of human memory CD4⁺ T cell clones primed by pathogens or vaccines.

    Science.gov (United States)

    Becattini, Simone; Latorre, Daniela; Mele, Federico; Foglierini, Mathilde; De Gregorio, Corinne; Cassotta, Antonino; Fernandez, Blanca; Kelderman, Sander; Schumacher, Ton N; Corti, Davide; Lanzavecchia, Antonio; Sallusto, Federica

    2015-01-23

    Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming. Copyright © 2015, American Association for the Advancement of Science.

  11. Pathoadaptation of a Human Pathogen Through Non-Coding Intergenic Mutations

    DEFF Research Database (Denmark)

    Khademi, Seyed Mohammad Hossein

    of opportunistic pathogen Pseudomonas aeruginosa in long-term chronic airway infections of Cystic fibrosis (CF) patients. Using sequenced genomes of P. aeruginosa isolated from this setting, 88 intergenic regions under positive selection for adaptive mutations within and across isolates of different P. aeruginosa......Most knowledge gained from evolutionary studies of bacteria in natural and experimental settings center around contribution of intragenic mutations on bacterial evolution. While cases of adaptive intergenic mutations have sometimes been reported or explored, none of these studies consider...... intergenic mutations in broader context as key players in evolutionary adaptation of bacteria. The focus of this thesis has been to provide novel insights on contributions of non-coding intergenic mutations in natural evolution of bacteria. The model system used for these investigations is adaptation...

  12. Genome-Wide Patterns of Recombination in the Opportunistic Human Pathogen Pseudomonas aeruginosa

    Science.gov (United States)

    Dettman, Jeremy R.; Rodrigue, Nicolas; Kassen, Rees

    2015-01-01

    The bacterium Pseudomonas aeruginosa is a significant cause of acute nosocomial infections as well as chronic respiratory infections in patients with cystic fibrosis (CF). Recent reports of the intercontinental spread of a CF-specific epidemic strain, combined with high intrinsic levels of antibiotic resistance, have made this opportunistic pathogen an important public health concern. Strain-specific differences correlate with variation in clinical outcomes of infected CF patients, increasing the urgency to understand the evolutionary origin of genetic factors conferring important phenotypes that enable infection, virulence, or resistance. Here, we describe the genome-wide patterns of homologous and nonhomologous recombination in P. aeruginosa, and the extent to which the genomes are affected by these diversity-generating processes. Based on whole-genome sequence data from 32 clinical isolates of P. aeruginosa, we examined the rate and distribution of recombination along the genome, and its effect on the reconstruction of phylogenetic relationships. Multiple lines of evidence suggested that recombination was common and usually involves short stretches of DNA (200–300 bp). Although mutation was the main source of nucleotide diversity, the import of polymorphisms by homologous recombination contributed nearly as much. We also identified the genomic regions with frequent recombination, and the specific sequences of recombinant origin within epidemic strains. The functional characteristics of the genes contained therein were examined for potential associations with a pathogenic lifestyle or adaptation to the CF lung environment. A common link between many of the high-recombination genes was their functional affiliation with the cell wall, suggesting that the products of recombination may be maintained by selection for variation in cell-surface molecules that allows for evasion of the host immune system. PMID:25480685

  13. Relaxation Methods for Strictly Convex Regularizations of Piecewise Linear Programs

    International Nuclear Information System (INIS)

    Kiwiel, K. C.

    1998-01-01

    We give an algorithm for minimizing the sum of a strictly convex function and a convex piecewise linear function. It extends several dual coordinate ascent methods for large-scale linearly constrained problems that occur in entropy maximization, quadratic programming, and network flows. In particular, it may solve exact penalty versions of such (possibly inconsistent) problems, and subproblems of bundle methods for nondifferentiable optimization. It is simple, can exploit sparsity, and in certain cases is highly parallelizable. Its global convergence is established in the recent framework of B -functions (generalized Bregman functions)

  14. Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species

    OpenAIRE

    Raymond, Fr?d?ric; Boisvert, S?bastien; Roy, Ga?tan; Ritt, Jean-Fran?ois; L?gar?, Danielle; Isnard, Amandine; Stanke, Mario; Olivier, Martin; Tremblay, Michel J.; Papadopoulou, Barbara; Ouellette, Marc; Corbeil, Jacques

    2011-01-01

    The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved to an average 16-fold mean coverage by next-generation DNA sequencing technologies. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described thus providing an opportunity for comparison with the completed genomes of pathogenic Leishmania species. A high synteny was observed between all sequenced Leishmania species. A limited number of chromosomal regions diverged between L. tarentolae a...

  15. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    Directory of Open Access Journals (Sweden)

    Hudler Petra

    2009-10-01

    Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  16. Control of highly pathogenic avian influenza in Quang Tri province, Vietnam: voices from the human-animal interface.

    Science.gov (United States)

    Farrell, Penny C; Hunter, Cynthia; Truong, Bui; Bunning, Michel

    2015-01-01

    Highly pathogenic avian influenza (HPAI) is caused by the haemagglutinin 5, neuraminidase 1 (H5N1) influenza A virus. Around 80% of households in rural Vietnam raise poultry, which provides food security and nutrition to their households and beyond. Of these, around 15-20% are semi-commercial producers, producing at least 28% of the country's chicken. Through learning the experiences of these semi-commercial farmers, this study aimed to explore the local understandings and sociocultural aspects of HPAI's impact, particularly the aetiology, diagnosis, and the prevention and control methods in one Vietnamese rural province. This study was conducted in Quang Tri province, Vietnam. Quang Tri province has eight districts. Five of these districts were at high risk of HPAI during the study period, of which three were selected for the present study. Within these three districts, six communes were randomly selected for the study from the list of intervention communes in Quang Tri province. Six out of the 26 intervention communes in Quang Tri were therefore selected. Participants were randomly selected and recruited from lists of semi-commercial farmers, village animal health workers, village human health workers and local authorities so that the study population (representative population) included an amount of variability similar to that of the wider population. A key benefit of this village-level control program was the residential proximity of animal and human health professionals. Participants were well aware of the typical clinical signs for avian influenza and of the reporting process for suspect cases. However there was extensive room for improvement in Quang Tri province regarding access to the HPAI vaccine, essential medical equipment for animal use, and available financial support. This qualitative research study provided an important insight for in-country policy makers and international stakeholders. It is vital that there are continued efforts to prevent and

  17. Regulation of sulphur assimilation is essential for virulence and affects iron homeostasis of the human-pathogenic mould Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Jorge Amich

    Full Text Available Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine catabolism, a process that has not been described before and that is MetR-dependent. The A. fumigatus MetR transcriptional activator is important for virulence in both leukopenic mice and an alternative mini-host model of aspergillosis, as it was essential for the development of pulmonary aspergillosis and supported the systemic dissemination of the fungus. MetR action under sulphur-starving conditions is further required for proper iron regulation, which links regulation of sulphur metabolism to iron homeostasis and demonstrates an unprecedented regulatory crosstalk. Taken together, this study provides evidence that regulation of sulphur assimilation is not only crucial for A. fumigatus virulence but also affects the balance of iron in this prime opportunistic pathogen.

  18. Regulation of sulphur assimilation is essential for virulence and affects iron homeostasis of the human-pathogenic mould Aspergillus fumigatus.

    Science.gov (United States)

    Amich, Jorge; Schafferer, Lukas; Haas, Hubertus; Krappmann, Sven

    2013-01-01

    Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine catabolism, a process that has not been described before and that is MetR-dependent. The A. fumigatus MetR transcriptional activator is important for virulence in both leukopenic mice and an alternative mini-host model of aspergillosis, as it was essential for the development of pulmonary aspergillosis and supported the systemic dissemination of the fungus. MetR action under sulphur-starving conditions is further required for proper iron regulation, which links regulation of sulphur metabolism to iron homeostasis and demonstrates an unprecedented regulatory crosstalk. Taken together, this study provides evidence that regulation of sulphur assimilation is not only crucial for A. fumigatus virulence but also affects the balance of iron in this prime opportunistic pathogen.

  19. Pathogenicity, Internal Transcribed Spacer-rDNA Variation, and Human Dispersal of Ceratocystis fimbriata on the Family Araceae.

    Science.gov (United States)

    Thorpe, Daniel J; Harrington, Thomas C; Uchida, Janice Y

    2005-03-01

    ABSTRACT Ceratocystis fimbriata is a complex of many cryptic, host-specialized species that causes wilt and canker of woody species and rot diseases of storage roots and corms of many economically important plants worldwide. With the exception of the family Araceae, all confirmed hosts of C. fimbriata are dicotyledonous plants. We hypothesized that the isolates from members of the family Araceae would form a monophyletic lineage specialized to infect these unique hosts. Analyses of sequences of the internal transcribed spacer (ITS) region of nuclear rDNA indicate that isolates and herbarium specimens of C. fimbriata from the family Araceae represent three different groups: an Xanthosoma/Syngonium group on corms of Xanthosoma spp. from the Caribbean region and on ornamental S. podophyllum from greenhouses in Florida, Hawaii, Australia, and Brazil; an inhame group on corms of Colocasia esculenta in Brazil; and a distantly related taro group on Colocasia esculenta in Hawaii and China and on X. sagittifolium in Fiji. Inoculations of three species of Araceae (Caladium bicolor, S. podophyllum, and Colocasia esculenta) showed that isolates from all three groups are pathogenic to these three hosts. Brazilian isolates from Mangifera indica and Ficus carica were only weakly pathogenic to Caladium and Syngonium sp. and were not pathogenic to Colocasia sp. Syngonium plants appeared to be most susceptible to isolates of the Xanthosoma/Syngonium group, and Colocasia plants were least susceptible to isolates from Syngonium spp. Thus, it appears that adaptations to the family Araceae have evolved more than once in the C. fimbriata complex. It is hypothesized that the three groups of C. fimbriata on the family Araceae are native to the Caribbean, Brazil, and Asia, respectively, but they have been spread elsewhere by humans.

  20. Rapid Identification of Emerging Human-Pathogenic Sporothrix Species with Rolling Circle Amplification

    NARCIS (Netherlands)

    Rodrigues, Anderson M; Najafzadeh, Mohammad J; de Hoog, G Sybren; de Camargo, Zoilo P

    2015-01-01

    Sporothrix infections are emerging as an important human and animal threat among otherwise healthy patients, especially in Brazil and China. Correct identification of sporotrichosis agents is beneficial for epidemiological surveillance, enabling implementation of adequate public-health policies and

  1. Food-borne human parasitic pathogens associated with household cockroaches and houseflies in Nigeria

    Directory of Open Access Journals (Sweden)

    Oyetunde T. Oyeyemi

    2016-03-01

    Full Text Available Cockroaches and houseflies pose significant public health threat owning to their ability to mechanically transmit human intestinal parasites and other disease-causing microorganisms. This study aims at assessing the vectoral capacity of cockroaches and houseflies in the transmission of human intestinal parasites. Intestinal parasite external surface contamination of 130 cockroaches and 150 houseflies caught within dwelling places in Ilishan-Remo town, Ogun State, Nigeria was determined. Cockroaches (six parasite species were more contaminated than houseflies (four parasite species. The most prevalent parasites were Trichuris trichiura (74.0% and hookworm (63.0% in houseflies and cockroaches respectively. There were significant differences in the prevalence of hookworm, T. trichiura and Taenia spp. isolated from cockroaches and houseflies (P < 0.05. There is high contamination of human intestinal parasites in cockroaches and houseflies in human dwelling places in the study area, thus they have the ability to transmit these parasites to unkempt food materials.

  2. Food-borne human parasitic pathogens associated with household cockroaches and houseflies in Nigeria

    OpenAIRE

    Oyeyemi, Oyetunde T.; Agbaje, Mariam O.; Okelue, Uchechi B.

    2016-01-01

    Cockroaches and houseflies pose significant public health threat owning to their ability to mechanically transmit human intestinal parasites and other disease-causing microorganisms. This study aims at assessing the vectoral capacity of cockroaches and houseflies in the transmission of human intestinal parasites. Intestinal parasite external surface contamination of 130 cockroaches and 150 houseflies caught within dwelling places in Ilishan-Remo town, Ogun State, Nigeria was determined. Cockr...

  3. Non-strictly black body spectrum from the tunnelling mechanism

    International Nuclear Information System (INIS)

    Corda, Christian

    2013-01-01

    The tunnelling mechanism is widely used to explain Hawking radiation. However, in many cases the analysis used to obtain the Hawking temperature only involves comparing the emission probability for an outgoing particle with the Boltzmann factor. Banerjee and Majhi improved this approach by explicitly finding a black body spectrum associated with black holes. Their result, obtained using a reformulation of the tunnelling mechanism, is in contrast to that of Parikh and Wilczek, who found an emission probability that is compatible with a non-strictly thermal spectrum. Using the recently identified effective state for a black hole, we solve this contradiction via a slight modification of the analysis by Banerjee and Majhi. The final result is a non-strictly black body spectrum from the tunnelling mechanism. We also show that for an effective temperature, we can express the corresponding effective metric using Hawking’s periodicity arguments. Potential important implications for the black hole information puzzle are discussed. -- Highlights: •We review an important result by Banerjee and Majhi on the tunnelling mechanism in the framework of Hawking radiation. •This result is in contrast to another result reported by Parikh and Wilczek. •We introduce the effective state of a black hole. •We explain the contrast via a slight modification of the analysis by Banerjee and Majhi. •We discuss potential important implications for the black hole information puzzle

  4. Immunoproteomic analysis of proteins expressed by two related pathogens, Burkholderia multivorans and Burkholderia cenocepacia, during human infection.

    Directory of Open Access Journals (Sweden)

    Minu Shinoy

    Full Text Available Burkholderia cepacia complex (Bcc is an opportunistic bacterial pathogen that causes chronic infections in people with cystic fibrosis (CF. It is a highly antibiotic resistant organism and Bcc infections are rarely cleared from patients, once they are colonized. The two most clinically relevant species within Bcc are Burkholderia cenocepacia and Burkholderia multivorans. The virulence of these pathogens has not been fully elucidated and the virulence proteins expressed during human infection have not been identified to date. Furthermore, given its antibiotic resistance, prevention of infection with a prophylactic vaccine may represent a better alternative than eradication of an existing infection. We have compared the immunoproteome of two strains each from these two species of Bcc, with the aim of identifying immunogenic proteins which are common to both species. Fourteen immunoreactive proteins were exclusive to both B. cenocepacia strains, while 15 were exclusive to B. multivorans. A total of 15 proteins were immunogenic across both species. DNA-directed RNA polymerase, GroEL, 38kDa porin and elongation factor-Tu were immunoreactive proteins expressed by all four strains examined. Many proteins which were immunoreactive in both species, warrant further investigations in order to aid in the elucidation of the mechanisms of pathogenesis of this difficult organism. In addition, identification of some of these could also allow the development of protective vaccines which may prevent colonisation.

  5. A molecular biological protocol to distinguish potentially human pathogenic Stenotrophomonas maltophilia from plant-associated Stenotrophomonas rhizophila.

    Science.gov (United States)

    Ribbeck-Busch, Kathrin; Roder, Anja; Hasse, Dirk; de Boer, Wietse; Martínez, José Luis; Hagemann, Martin; Berg, Gabriele

    2005-11-01

    In recent years, the importance of the Gram-negative bacterium Stenotrophomonas as an opportunistic pathogen as well as in biotechnology has increased. The aim of the present study was to develop new methods for distinguishing between strains closely related to the potentially human pathogenic Stenotrophomonas maltophilia and those closely related to the plant-associated Stenotrophomonas rhizophila. To accomplish this, 58 strains were characterized by 16S rDNA sequencing and amplified ribosomal DNA restriction analysis (ARDRA), and the occurrence of specific functional genes. Based on 16S rDNA sequences, an ARDRA protocol was developed which allowed differentiation between strains of the S. maltophilia and the S. rhizophila group. As it was known that only salt-treated cells of S. rhizophila were able to synthesize the compatible solute glucosylglycerol (GG), the ggpS gene responsible for GG synthesis was used for differentiation between both species and it was confirmed that it only occurred in S. rhizophila strains. As a further genetic marker the smeD gene, which is part of the genes coding for the multidrug efflux pump SmeDEF from S. maltophilia, was used. Based on the results we propose a combination of fingerprinting techniques using the 16S rDNA and the functional genes ggpS and smeD to distinguish both Stenotrophomonas species.

  6. The multifaceted resources and microevolution of the successful human and animal pathogen methicillin-resistant Staphylococcus aureus

    Science.gov (United States)

    Figueiredo, Agnes Marie Sá; Ferreira, Fabienne Antunes

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important bacterial pathogens based on its incidence and the severity of its associated infections. In addition, severe MRSA infections can occur in hospitalised patients or healthy individuals from the community. Studies have shown the infiltration of MRSA isolates of community origin into hospitals and variants of hospital-associated MRSA have caused infections in the community. These rapid epidemiological changes represent a challenge for the molecular characterisation of such bacteria as a hospital or community-acquired pathogen. To efficiently control the spread of MRSA, it is important to promptly detect the mecA gene, which is the determinant of methicillin resistance, using a polymerase chain reaction-based test or other rapidly and accurate methods that detect the mecA product penicillin-binding protein (PBP)2a or PBP2’. The recent emergence of MRSA isolates that harbour a mecA allotype, i.e., the mecC gene, infecting animals and humans has raised an additional and significant issue regarding MRSA laboratory detection. Antimicrobial drugs for MRSA therapy are becoming depleted and vancomycin is still the main choice in many cases. In this review, we present an overview of MRSA infections in community and healthcare settings with focus on recent changes in the global epidemiology, with special reference to the MRSA picture in Brazil. PMID:24789555

  7. The multifaceted resources and microevolution of the successful human and animal pathogen methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Agnes Marie Sá Figueiredo

    2014-06-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA is one of the most important bacterial pathogens based on its incidence and the severity of its associated infections. In addition, severe MRSA infections can occur in hospitalised patients or healthy individuals from the community. Studies have shown the infiltration of MRSA isolates of community origin into hospitals and variants of hospital-associated MRSA have caused infections in the community. These rapid epidemiological changes represent a challenge for the molecular characterisation of such bacteria as a hospital or community-acquired pathogen. To efficiently control the spread of MRSA, it is important to promptly detect the mecA gene, which is the determinant of methicillin resistance, using a polymerase chain reaction-based test or other rapidly and accurate methods that detect the mecA product penicillin-binding protein (PBP2a or PBP2’. The recent emergence of MRSA isolates that harbour a mecA allotype, i.e., the mecC gene, infecting animals and humans has raised an additional and significant issue regarding MRSA laboratory detection. Antimicrobial drugs for MRSA therapy are becoming depleted and vancomycin is still the main choice in many cases. In this review, we present an overview of MRSA infections in community and healthcare settings with focus on recent changes in the global epidemiology, with special reference to the MRSA picture in Brazil.

  8. Pathogenic Potential to Humans of Bovine Escherichia coli O26, Scotland

    Science.gov (United States)

    Rosser, Tracy; Allison, Lesley J.; Courcier, Emily; Evans, Judith; McKendrick, Iain J.; Pearce, Michael C.; Handel, Ian; Caprioli, Alfredo; Karch, Helge; Hanson, Mary F.; Pollock, Kevin G.J.; Locking, Mary E.; Woolhouse, Mark E.J.; Matthews, Louise; Low, J. Chris; Gally, David L.

    2012-01-01

    Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin–producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx2 in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26–associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx2 phage acquisition. PMID:22377426

  9. Diversity and abundance of human-pathogenic fungi associated with pigeon faeces in urban environments.

    Science.gov (United States)

    Lee, Won Dong; Fong, Jonathan J; Eimes, John A; Lim, Young Woon

    2017-09-01

    Pathogenic fungi are a growing health concern worldwide, particularly in large, densely populated cities. The dramatic upsurge of pigeon populations in cities has been implicated in the increased incidence of invasive fungal infections. In this study, we used a culture-independent, high-throughput sequencing approach to describe the diversity of clinically relevant fungi (CRF) associated with pigeon faeces and map the relative abundance of CRF across Seoul, Korea. In addition, we tested whether certain geographical, sociological and meteorological factors were significantly associated with the diversity and relative abundance of CRF. Finally, we compared the CRF diversity of fresh and old pigeon faeces to identify the source of the fungi and the role of pigeons in dispersal. Our results demonstrated that both the composition and relative abundance of CRF are unevenly distributed across Seoul. The green area ratio and the number of multiplex houses were positively correlated with species diversity, whereas wind speed and number of households were negatively correlated. The number of workers and green area ratio were positively correlated with the relative abundance of CRF, whereas wind speed was negatively correlated. Because many CRF were absent in fresh faeces, we inferred that most species cannot survive the gastrointestinal tract of pigeons and instead are likely transmitted through soil or air and use pigeon faeces as a substrate for proliferation. © 2017 John Wiley & Sons Ltd.

  10. Epidemiology of antifungal resistance in human pathogenic yeasts: current viewpoint and practical recommendations for management.

    Science.gov (United States)

    Farmakiotis, Dimitrios; Kontoyiannis, Dimitrios P

    2017-09-01

    In this review, we describe the epidemiology and clinical significance of resistance in Candida spp. and other non-Cryptococcus yeasts. The rise in echinocandin resistance, azole resistance and cross-resistance to two or more antifungal classes [multidrug resistance (MDR)] has been a worrisome trend, mainly in US large tertiary and oncology centres, particularly as it relates to Candida glabrata. Candida kefyr is also a concern as it can be resistant to echinocandins and polyenes, especially in patients with haematological malignancies. Lately, Candida auris has drawn a lot of attention: this uncommon Candida spp. is the first globally emerging fungal pathogen that exhibits MDR and strong potential for nosocomial transmission. Its almost simultaneous spread in four continents could be indicative of increasing selection pressures from the use of antifungal agents. Echinocandin non-susceptibility is also common among non-Candida, non-Cryptococcus yeasts. As Candida resistance patterns reflect, in part, institutional practices of antifungal administration, the benefits of antifungal stewardship protocols are increasingly recognised and endorsed in recent guidelines. Development of rapid diagnostic methods for detecting or ruling out the presence of candidaemia and antifungal resistance, as well as discovery of novel antifungals, are key priorities in medical mycology research. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. Transcription and processing of mitochondrial RNA in the human pathogen Acanthamoeba castellanii.

    Science.gov (United States)

    Accari, Jessica; Barth, Christian

    2015-07-01

    The size, structure, gene content and organisation of mitochondrial genomes can be highly diverse especially amongst the protists. We investigated the transcription and processing of the mitochondrial genome of the opportunistic pathogen Acanthamoeba castellanii and here we present a detailed transcription map of the 41.6 kb genome that encodes 33 proteins, 16 tRNAs and 2 rRNAs. Northern hybridisation studies identified six major polycistronic transcripts, most of which are co-transcriptionally processed into smaller mono-, di- and tricistronic RNAs. The maturation of the polycistronic transcripts is likely to involve endonucleolytic cleavage where tRNAs serve as processing signals. Reverse transcription polymerase chain reactions across the intervening regions between the six major polycistronic transcripts suggest that these transcripts were once part of an even larger transcript. Our findings indicate that the mitochondrial genome of A. castellanii is transcribed from only one or two promoters, very similar to the mode of transcription in the mitochondria of its close relative Dictyostelium discoideum, where transcription is known to occur from only a single transcription initiation site. Transcription initiation from a minimal number of promoters despite a large genome size may be an emerging trend in the mitochondria of protists. Copyright © 2015. Published by Elsevier B.V.

  12. Biosynthesis of Cu, ZVI, and Ag nanoparticles using Dodonaea viscosa extract for antibacterial activity against human pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Kiruba Daniel, S. C. G.; Vinothini, G. [Anna University of Technology, Tiruchirappalli, Department of Nanoscience and Technology (India); Subramanian, N. [Anna University of Technology, Tiruchirappalli, Department of Pharmaceutical Technology (India); Nehru, K. [Anna University of Technology, Tiruchirappalli, Department of Chemistry (India); Sivakumar, M., E-mail: muthusiva@gmail.com [Anna University of Technology, Tiruchirappalli, Department of Nanoscience and Technology (India)

    2013-01-15

    Biosynthesis of copper, zero-valent iron (ZVI), and silver nanoparticles using leaf extract of Dodonaea viscosa has been investigated in this report. There are no additional surfactants/polymers used as capping or reducing agents for these syntheses. The synthesized nanoparticles were characterized by UV-Vis spectroscopy, X-ray diffraction, atomic force microscopy, and high-resolution transmission electron microscopy. The phase analysis was performed using selected area electron diffraction. The pH dependence of surface plasmon resonance and subsequent size variation has been determined. The synthesized nanoparticles showed spherical morphology and the average size of 29, 27, and 16 nm for Cu, ZVI, and Ag nanoparticles, respectively. Finally, biosynthesized Cu, ZVI, and Ag nanoparticles were tested against human pathogens viz. Gram-negative Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens and Gram-positive Staphylococcus aureus and Bacillus subtilis, and showed good antimicrobial activity.

  13. Biosynthesis of silver nanoparticles from the marine seaweed Sargassum wightii and their antibacterial activity against some human pathogens

    Science.gov (United States)

    Shanmugam, N.; Rajkamal, P.; Cholan, S.; Kannadasan, N.; Sathishkumar, K.; Viruthagiri, G.; Sundaramanickam, A.

    2014-10-01

    In this paper, we have reported on biological synthesis of nano-sized silver and its antibacterial activity against human pathogens. The nanoparticles of silver were formed by the reduction of silver nitrate to aqueous silver metal ions during exposure to the extract of marine seaweed Sargassum wightii. The optical properties of the obtained silver nanoparticles were characterized using UV-visible absorption and room temperature photoluminescence. The X-ray diffraction results reveal that the synthesized silver nanoparticles are in the cubic phase. The existence of functional groups was identified using Fourier transform infrared spectroscopy. The morphology and size of the synthesized particles were studied with atomic force microscope and high-resolution transmission electron microscope measurements. The synthesized nanoparticles have an effective antibacterial activity against S. aureus, K. pneumoniae, and S. typhi.

  14. Biosynthesis of Cu, ZVI, and Ag nanoparticles using Dodonaea viscosa extract for antibacterial activity against human pathogens

    International Nuclear Information System (INIS)

    Kiruba Daniel, S. C. G.; Vinothini, G.; Subramanian, N.; Nehru, K.; Sivakumar, M.

    2013-01-01

    Biosynthesis of copper, zero-valent iron (ZVI), and silver nanoparticles using leaf extract of Dodonaea viscosa has been investigated in this report. There are no additional surfactants/polymers used as capping or reducing agents for these syntheses. The synthesized nanoparticles were characterized by UV–Vis spectroscopy, X-ray diffraction, atomic force microscopy, and high-resolution transmission electron microscopy. The phase analysis was performed using selected area electron diffraction. The pH dependence of surface plasmon resonance and subsequent size variation has been determined. The synthesized nanoparticles showed spherical morphology and the average size of 29, 27, and 16 nm for Cu, ZVI, and Ag nanoparticles, respectively. Finally, biosynthesized Cu, ZVI, and Ag nanoparticles were tested against human pathogens viz. Gram-negative Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens and Gram-positive Staphylococcus aureus and Bacillus subtilis, and showed good antimicrobial activity.

  15. Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif.

    Directory of Open Access Journals (Sweden)

    Teresia Hallström

    Full Text Available Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram-positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13 bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352-374. This specific interaction leaves the terminal complement complex (TCC regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response.

  16. Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis.

    Science.gov (United States)

    Lenzo, Jason C; O'Brien-Simpson, Neil M; Orth, Rebecca K; Mitchell, Helen L; Dashper, Stuart G; Reynolds, Eric C

    2016-09-01

    Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Dishwashers - a man-made ecological niche accommodating human opportunistic fungal pathogens.

    NARCIS (Netherlands)

    Zalar, P.; Novak, M.; de Hoog, G.S.; Gunde - Cimerman, N.

    2011-01-01

    Habitats in human households may accommodate microorganisms outside the common spectrum of ubiquitous saprobes. Enrichment of fungi that may require specific environmental conditions was observed in dishwashers, 189 of which were sampled in private homes of 101 towns or communities. One-hundred-two

  18. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest

    NARCIS (Netherlands)

    Hagen, F.; Ceresini, P.C.; Polacheck, I.; Ma, H.; van Nieuwerburgh, F.; Gabaldon, T.; Kagan, S.; Pursall, E.R.; Hoogveld, H.L.; van Iersel, L.J.; Klau, G.W.; Kelk, S.M.; Stougie, L.; Bartlett, K.H.; Voelz, K.; Pryszcz, L.P.; Castaneda, E.; Lazera, M.; Meyer, W.; Deforce, D.; Meis, J.F.G.M.; May, R.C.; Klaassen, C.H.W.; Boekhout, T.

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause

  19. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest.

    NARCIS (Netherlands)

    Hagen, F.; Ceresini, P.C.; Polacheck, I.; Ma, H.; Nieuwerburgh, F. van; Gabaldón, T.; Kagan, S.; Pursall, E.R.; Hoogveld, H.L.; Iersel, L.J. van; Klau, G.W.; Kelk, S.M.; Stougie, L.; Bartlett, K.H.; Voelz, K.; Pryszcz, L.P.; Castañeda, E.; Lazera, M.; Meyer, W.; Deforce, D.; Meis, J.F.G.M.; May, R.C.; Klaassen, C.H.; Boekhout, T.

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause

  20. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an

  1. Surface Enhanced Raman Spectroscopy for the Rapid Detection and Identification of Microbial Pathogens in Human Serum

    Science.gov (United States)

    2014-12-11

    FOR OFFICIAL USE ONLY 4 ABBREVIATIONS %CV Coefficient of variation AgNR Silver nanorod A. baumannii Acinetobacter baumannii ADP...and 1 mm depth. Bacterial culture and cell count determination Bacterial species of Acinetobacter baumannii (A. baumannii , ST-3), Escherichia coli...identification of bacteria in pooled human sera. Methods: Species of Acenitobacter baumannii , Escherichia coli, Klebsiella pneumoniae, Staphylococcus

  2. Effects of biochar on reducing the abundance of oxytetracycline, antibiotic resistance genes, and human pathogenic bacteria in soil and lettuce.

    Science.gov (United States)

    Duan, Manli; Li, Haichao; Gu, Jie; Tuo, Xiaxia; Sun, Wei; Qian, Xun; Wang, Xiaojuan

    2017-05-01

    Antibiotics and antibiotic resistance genes (ARGs) in soil can affect human health via the food chain. Biochar is a soil amendment but its impacts on ARGs and the microbial communities associated with soil and vegetables are unclear. Therefore, we established three lettuce pot culture experiments, i.e., O300: 300 mg/kg oxytetracycline (OTC), BO300: 300 mg/kg OTC + 2% biochar, and a control without OTC or biochar. We found that under BO300, the relative abundances of ARGs were reduced by 51.8%, 43.4%, and 44.1% in lettuce leaves, roots, and soil, respectively, compared with O300. intI1 was highly abundant in soil and lettuce, and it co-occurred with some ARGs (tetW, ermF, and sul1). Redundancy analysis and network analysis indicated that the bacterial community succession was the main mechanism that affected the variations in ARGs and intI1. The reduction of Firmicutes due to the biochar treatment of soil and lettuce was the main factor responsible for the removal of tetracycline resistance genes in leaves. Biochar application led to the disappearance of human pathogenic bacteria (HPB), which was significantly correlated with the abundances of ermF and ermX. In summary, biochar is an effective farmland amendment for reducing the abundances of antibiotics, ARGs, and HPB in order to ensure the safety of vegetables and protect human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. [The role of natural environment in spreading of hantavirus--model of the correlation between host, pathogen and human infections].

    Science.gov (United States)

    Baumann, Anna; Dudek, Dorota; Sadkowska-Todys, Małgorzata

    2007-01-01

    The environmental changes caused by humans influence ecosystem and thus have significant impact on occurrence of emerging and re-emerging diseases. The hantavirus infection belong to the one of them. The aim of this paper was to present current knowledge about relationship between hantavirus, their natural host and the spread of the infection to people. Rodents constitute both the natural host of the hantaviruses and the reservoir of hantavirus for environment. Circulation of the virus in the rodent population is crucial to maintain the virus in the environment. The individual characteristics of rodents influence on risk of infection with hantavirus. However, this relationship is still unexplained. Risk of pathogen exposure often increases with age and behavioral differences associated with the sex of the susceptible individual. Mating behaviors seem to play an important role in the spread of the virus among rodents. Human incidence of hantavirus infection has in general been found to correlate to the population size of rodent host especially in the model of nephropathia epidemica (NE; a mild form of HFRS), Puumala virus (PUU) and bank voles. The occurrence of hantavirus infections in humans is assumed to rise as a secondary effect from altered population sizes of rodents in a changing environment due to e.g. mast years, forest fragmentation, global warming.

  4. Effect of Inulin on Proteome Changes Induced by Pathogenic Lipopolysaccharide in Human Colon.

    Science.gov (United States)

    Guarino, Michele Pier Luca; Altomare, Annamaria; Barera, Simone; Locato, Vittoria; Cocca, Silvia; Franchin, Cinzia; Arrigoni, Giorgio; Vannini, Candida; Grossi, Sarah; Campomenosi, Paola; Pasqualetti, Valentina; Bracale, Marcella; Alloni, Rossana; De Gara, Laura; Cicala, Michele

    2017-01-01

    In the present study, the protective role of inulin against lipopolysaccharide (LPS)-induced oxidative stress was evaluated on human colonic mucosa using a proteomic approach. Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and overlaid with Krebs (control), LPS or LPS+ inulin IQ solution. The solutions on the submucosal side (undernatants) were collected following 30 min of mucosal exposure. iTRAQ based analysis was used to analyze the total soluble proteomes from human colonic mucosa and submucosa treated with different undernatants. Human colonic muscle strips were exposed to the undernatants to evaluate the response to acetylcholine. Inulin exposure was able to counteract, in human colonic mucosa, the LPS-dependent alteration of some proteins involved in the intestinal contraction (myosin light chain kinase (MLCK), myosin regulatory subunit (MYL)), to reduce the up-regulation of two proteins involved in the radical-mediated oxidative stress (the DNA-apurinic or apyrimidinic site) lyase) APEX1 and the T-complex protein 1 subunit eta (CCT7) and to entail a higher level of some detoxification enzymes (the metallothionein-2 MT2A, the glutathione-S-transferase K GSTk, and two UDP- glucuronosyltransferases UGT2B4, UGT2B17). Inulin exposure was also able to prevent the LPS-dependent intestinal muscle strips contraction impairment and the mucosa glutathione level alterations. Exposure of colonic mucosa to inulin seems to prevent LPS-induced alteration in expression of some key proteins, which promote intestinal motility and inflammation, reducing the radical-mediated oxidative stress.

  5. A putative marker for human pathogenic strains of Anaplasma phagocytophilum correlates with geography and host, but not human tropism.

    Science.gov (United States)

    Foley, Janet; Stephenson, Nicole; Cubilla, Michelle Pires; Qurollo, Barbara; Breitschwerdt, Edward B

    2016-03-01

    Anaplasma phagocytophilum is an Ixodes species tick-transmitted bacterium that is capable of infecting a variety of host species, although there is a diversity of bacterial strains with differing host tropism. Recent analysis of A. phagocytophilum strains suggested that "drhm", a gene locus designated "distantly related to human marker" (drhm), which was predicted to be an integral membrane protein with possible transporter functions was not present in available canine and human isolates. By assessing 117 strains from 14 host species from across the US, we extended this analysis. Phylogenetic clades were associated with geography, but not host species. Additionally, a virulent clade that lacks drhm and infects dogs, horses, and humans in northeastern US was identified. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species.

    Science.gov (United States)

    Mitri, Christian; Jacques, Jean-Claude; Thiery, Isabelle; Riehle, Michelle M; Xu, Jiannong; Bischoff, Emmanuel; Morlais, Isabelle; Nsango, Sandrine E; Vernick, Kenneth D; Bourgouin, Catherine

    2009-09-01

    Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island (PRI) of the A. gambiae genome. The APL1 family of leucine-rich repeat (LRR) proteins was highlighted by candidate gene studies in the PRI, and is comprised of paralogs APL1A, APL1B and APL1C that share > or =50% amino acid identity. Here, we present a functional analysis of the joint response of APL1 family members during mosquito infection with human and rodent Plasmodium species. Only paralog APL1A protected A. gambiae against infection with the human malaria parasite P. falciparum from both the field population and in vitro culture. In contrast, only paralog APL1C protected against the rodent malaria parasites P. berghei and P. yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2 pathway, while protection against P. berghei infection was shown to require Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2-F isoform of Rel2 confers protection against P. falciparum. Protection correlates with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting that the Rel2-S anti-parasite phenotype results at least in part from its transcriptional control over APL1A. These results indicate that distinct members of the APL1 gene family display a mutually exclusive protective effect against different classes of Plasmodium parasites. It appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. It is known that insect innate immune pathways can distinguish between grossly different microbes such as Gram-positive bacteria, Gram-negative bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between classes of

  7. Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species.

    Directory of Open Access Journals (Sweden)

    Christian Mitri

    2009-09-01

    Full Text Available Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island (PRI of the A. gambiae genome. The APL1 family of leucine-rich repeat (LRR proteins was highlighted by candidate gene studies in the PRI, and is comprised of paralogs APL1A, APL1B and APL1C that share > or =50% amino acid identity. Here, we present a functional analysis of the joint response of APL1 family members during mosquito infection with human and rodent Plasmodium species. Only paralog APL1A protected A. gambiae against infection with the human malaria parasite P. falciparum from both the field population and in vitro culture. In contrast, only paralog APL1C protected against the rodent malaria parasites P. berghei and P. yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2 pathway, while protection against P. berghei infection was shown to require Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2-F isoform of Rel2 confers protection against P. falciparum. Protection correlates with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting that the Rel2-S anti-parasite phenotype results at least in part from its transcriptional control over APL1A. These results indicate that distinct members of the APL1 gene family display a mutually exclusive protective effect against different classes of Plasmodium parasites. It appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. It is known that insect innate immune pathways can distinguish between grossly different microbes such as Gram-positive bacteria, Gram-negative bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between

  8. A strategy for synthesis of pathogenic human immunoglobulin free light chains in E. coli.

    Directory of Open Access Journals (Sweden)

    Paola Rognoni

    Full Text Available Monoclonal immunoglobulin light chains are normally synthesized in excess compared to the heavy chain partners and can be detected in serum and urine ("free" LC. Occasionally free LC are per se cause of organ toxicity, as in free LC-related disorders. In AL amyloidosis, the most common of these conditions, free LC with peculiar biophysical properties related to their primary structure damage target organs and organize in amyloid fibrils. Unlimited availability of well-characterized free LC is instrumental to investigate the toxic effect of these proteins and to study their interactions with targets. We present a straightforward strategy to obtain recombinant monoclonal free LC by using a bacterial system. These proteins, expressed as inclusion bodies, were subjected to solubilization and refolding procedures to recover them in native form. To minimize differences from the circulating natural LC, full-length recombinant LC were expressed, i.e. complete of variable and constant regions, with the original amino acid sequence along the entire protein, and with no purification tags. The strategy was exploited to generate free LC from three AL amyloidosis patients. After purification, recombinant proteins were biochemically characterized and compared to the natural Bence Jones protein isolated from one of the patients. Results showed that the recombinant free LC were properly folded and formed homodimers in solution, similar to the natural Bence Jones protein used for comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed amyloid fibrils in vitro. We believe that the present strategy represents a valuable tool to speed research in free LC-related disorders.

  9. A Potential New Human Pathogen Belonging to Helicobacter Genus, Identified in a Bloodstream Infection

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    Nathalie L. van der Mee-Marquet

    2017-12-01

    Full Text Available We isolated from aerobic and anaerobic blood culture bottles from a febrile patient, a Helicobacter-like Gram negative, rod-shaped bacterium that MALDI-TOF MS failed to identify. Blood agar cultures incubated in a microaerobic atmosphere revealed a motile Gram negative rod, which was oxidase, catalase, nitrate reductase, esterase, and alkaline phosphatase positive. It grew at 42°C with no detectable urease activity. Antimicrobial susceptibility testing showed that the organism was susceptible to beta-lactams, gentamicin, erythromycin, and tetracycline but resistant to ciprofloxacin. Electronic microscopy analysis revealed a 3 × 0.5 μm curved rod bacterium harboring two sheathed amphitrichous flagella. Whole genome sequencing revealed a genome 1,708,265 base-pairs long with a GC content of 37.80% and a total of 1,697 coding sequences. The genomic analyses using the nucleotide sequences of the 16S rRNA gene, hsp60 and gyrB genes, as well as the GyrA protein sequence, and the results of Average Nucleotide Identity and in silico DNA-DNA hybridization suggest evidence for a novel Helicobacter species close to Helicobacter equorum and belonging to the group of enterohepatic Helicobacter species. As soon as the particular peptide mass fingerprint of this pathogen is added to the spectral databases, MALDI-TOF MS technology will improve its identification from clinical specimens, especially in case of “sterile infection”. We propose to associate the present strain with the Latin name of the place of isolation; Caesarodunum (Tours, France and suggest “Helicobacter caesarodunensis” for further description of this new bacterium.

  10. Differential activity of a lectin from Solieria filiformis against human pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    M.L. Holanda

    2005-12-01

    Full Text Available A lectin isolated from the red alga Solieria filiformis was evaluated for its effect on the growth of 8 gram-negative and 3 gram-positive bacteria cultivated in liquid medium (three independent experiments/bacterium. The lectin (500 µg/mL stimulated the growth of the gram-positive species Bacillus cereus and inhibited the growth of the gram-negative species Serratia marcescens, Salmonella typhi, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus sp, and Pseudomonas aeruginosa at 1000 µg/mL but the lectin (10-1000 µg/mL had no effect on the growth of the gram-positive bacteria Staphylococcus aureus and B. subtilis, or on the gram-negative bacteria Escherichia coli and Salmonella typhimurium. The purified lectin significantly reduced the cell density of gram-negative bacteria, although no changes in growth phases (log, exponential and of decline were observed. It is possible that the interaction of S. filiformis lectin with the cell surface receptors of gram-negative bacteria promotes alterations in the flow of nutrients, which would explain the bacteriostatic effect. Growth stimulation of the gram-positive bacterium B. cereus was more marked in the presence of the lectin at a concentration of 1000 µg/mL. The stimulation of the growth of B. cereus was not observed when the lectin was previously incubated with mannan (125 µg/mL, its hapten. Thus, we suggest the involvement of the binding site of the lectin in this effect. The present study reports the first data on the inhibition and stimulation of pathogenic bacterial cells by marine alga lectins.

  11. A mathematical model for removal of human pathogenic viruses and bacteria by slow sand filtration under variable operational conditions

    NARCIS (Netherlands)

    Schijven, J.F.; Berg, H.H.J.L. van den; Colin, M.; Dullemont, Y.; Hijnen, W.A.M.; Magic-Knezev, A.; Oorthuizen, W.A.; Wubbels, G.

    2013-01-01

    Slow sand filtration (SSF) in drinking water production removes pathogenic microorganisms, but detection limits and variable operational conditions complicate assessment of removal efficiency. Therefore, amodel was developed to predict removal ofhuman pathogenic viruses and bacteria as a function

  12. Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus.

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    Matteo Porotto

    Full Text Available We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV and Hendra (HeV viruses. In the new approach, artificial cell-like particles (protocells presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development.

  13. Expression of RORγt Marks a Pathogenic Regulatory T Cell Subset in Human Colon Cancer

    OpenAIRE

    Blatner, Nichole R.; Mulcahy, Mary F.; Dennis, Kristen L.; Scholtens, Denise; Bentrem, David J.; Phillips, Joseph D.; Ham, Soo; Sandall, Barry P.; Khan, Mohammad W.; Mahvi, David M.; Halverson, Amy L.; Stryker, Steven J.; Boller, Anne-Marie; Singal, Ashima; Sneed, Rebekka K.

    2012-01-01

    The role of regulatory T cells (Tregs) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating Tregs can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, Tregs have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different Treg subsets. We report the prefer...

  14. Ganciclovir inhibits human adenovirus replication and pathogenicity in permissive immunosuppressed Syrian hamsters.

    Science.gov (United States)

    Ying, Baoling; Tollefson, Ann E; Spencer, Jacqueline F; Balakrishnan, Lata; Dewhurst, Stephen; Capella, Cristina; Buller, R Mark L; Toth, Karoly; Wold, William S M

    2014-12-01

    Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Effects of a strict cutoff on Quantum Field Theory

    International Nuclear Information System (INIS)

    Sturnfield, J.F.

    1987-01-01

    Standard Quantum Field Theory has a number of integrals which are infinite. Although these are eliminated for some cases by renormalization, this aspect of the theory is not fully satisfactory. A number of theories with fundamental lengths have been introduced as alternatives and it would be useful to be able to distinguish between them. In particular, the effects that a strict cutoff would have on Quantum Field Theory is studied. It is noted that care must be taken in the method used to apply a strict cutoff. This lead to considering a theory where the cutoffs are defined by restricting each internal line. This theory is only piece-wise analytic. The resulting scattering matrix is frame dependent, yet the theory still satisfies the special relativity view that all frames are subjectively identical. The renormalization of this theory is finite. The change in mass from the electron self-energy will be a spinor operator. The main distinctions of this theory from standard theory will occur at super high energies. New poles and resonances which arise from new endpoint singularities will be found. The locations of these singularities will be frame dependent. Some of these singularities will correspond to creations or interactions of the normal particles with tachyons. It will be shown that for the one loop diagram, the form of the cutoff singularities are closely related to the standard singularities. When there is more than one loop, there can appear some new type of behavior. In particular, a cube root type of behavior in the two loop self-energy diagram will be found. Also the asymptotic behavior of the ladder diagram is studied

  16. Toxoplasma gondii-A Gastrointestinal Pathogen Associated with Human Brain Diseases.

    Science.gov (United States)

    Severance, E G; Xiao, J; Jones-Brando, L; Sabunciyan, S; Li, Y; Pletnikov, M; Prandovszky, E; Yolken, R

    2016-01-01

    Serious psychiatric disorders such as schizophrenia, bipolar disorder, and major depression are important causes of mortality and morbidity worldwide. While these are primarily diseases involving altered brain functioning, numerous studies have documented increased rates of gastrointestinal inflammation and dysfunction in many individuals with these disorders. Toxoplasma gondii is an apicomplexan protozoan intracellular parasite with a widespread distribution in both developed and developing countries. Toxoplasma organisms enter the ecosystem through the shedding of oocysts by Toxoplasma-infected felines. In almost all cases of postnatal human infection, Toxoplasma enters its hosts through the intestinal tract either by the ingestion of oocysts or by the consumption of meat from food animals which themselves were infected by Toxoplasma oocysts. It had previously been thought that most cases of Toxoplasma infection in immune competent children and adults were inapparent and asymptomatic. However, recent studies cast doubt on this concept as exposure to Toxoplasma has been associated with a range of acute and chronic symptoms. Of particular note has been the finding of an increased rate of a range of neurological and psychiatric disorders associated with serological evidence of Toxoplasma exposure. A role of Toxoplasma infection in brain diseases is also supported by the consistent finding of altered cognition and behavior in animal models of infections. Much of the attention relating to the role of Toxoplasma infection in neuropsychiatric disorders has focused on the brain, where Toxoplasma tissue cysts can persist for extended periods of time. However, recent discoveries relating to the role of the gastrointestinal tract in cognition and behavior suggest that Toxoplasma may also increase susceptibility to human brain diseases through immune activation, particularly involving the gastrointestinal mucosa. The study of the pathways relating to the pathobiology and

  17. Investigation of touch-sensitive responses by hyphae of the human pathogenic fungus Candida albicans.

    Science.gov (United States)

    Gow, N A; Perera, T H; Sherwood-Higham, J; Gooday, G W; Gregory, D W; Marshall, D

    1994-01-01

    Candida albicans is a fungus that commonly infects the mucosal surface of humans. The hyphal growth form of this fungus may initiate the primary invasion of the host. Here we show that hyphae respond thigmotropically and morphologically to cues such as the presence of a surface, pores, grooves and ridges. Growth on some firm surfaces elicits a helical growth response. Hyphae follow grooves and ridges of inert substrates and penetrate pores of filtration membranes. Our in vitro experiments suggest that thigmotropism may enhance the ability of a hypha to invade epithelia of a host at sites of weakened integrity.

  18. Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

    Directory of Open Access Journals (Sweden)

    Anne Le Flèche-Matéos

    2012-01-01

    Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

  19. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.

    Directory of Open Access Journals (Sweden)

    Dominick J Laddy

    Full Text Available BACKGROUND: The persistent evolution of highly pathogenic avian influenza (HPAI highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. METHODS AND FINDINGS: Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA, N1 neuraminidase (pN1NA, and nucleoprotein antigen (pNP. Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40 were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. CONCLUSIONS: By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the

  20. ATP-Binding Cassette (ABC) Transporters of the Human Respiratory Tract Pathogen, Moraxella catarrhalis: Role in Virulence.

    Science.gov (United States)

    Murphy, Timothy F; Brauer, Aimee L; Johnson, Antoinette; Kirkham, Charmaine

    2016-01-01

    Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens. In the present study, we performed a comprehensive assessment of 19 SBPs of 15 ABC transporter systems in the M. catarrhalis genome by engineering knockout mutants and studying their role in assays that assess mechanisms of infection. The capacity of M. catarrhalis to survive and grow in the nutrient-limited and hostile environment of the human respiratory tract, including intracellular growth, account in part for its virulence. The results show that ABC transporters that mediate uptake of peptides, amino acids, cations and anions play important roles in pathogenesis by enabling M. catarrhalis to 1) grow in nutrient-limited conditions, 2) invade and survive in human respiratory epithelial cells and 3) persist in the lungs in a murine pulmonary clearance model. The knockout mutants of SBPs and ABC transporters showed different patterns of activity in the assay systems, supporting the conclusion that different SBPs and ABC transporters function at different stages in the pathogenesis of infection. These results indicate that ABC transporters are nutritional virulence factors, functioning to enable the survival of M catarrhalis in the diverse microenvironments of the respiratory tract. Based on the role of ABC transporters as virulence factors of M. catarrhalis, these molecules represent potential drug targets to eradicate the organism from the human respiratory tract.

  1. Pathogen-Host Associations and Predicted Range Shifts of Human Monkeypox in Response to Climate Change in Central Africa

    Science.gov (United States)

    Thomassen, Henri A.; Fuller, Trevon; Asefi-Najafabady, Salvi; Shiplacoff, Julia A. G.; Mulembakani, Prime M.; Blumberg, Seth; Johnston, Sara C.; Kisalu, Neville K.; Kinkela, Timothée L.; Fair, Joseph N.; Wolfe, Nathan D.; Shongo, Robert L.; LeBreton, Matthew; Meyer, Hermann; Wright, Linda L.; Muyembe, Jean-Jacques; Buermann, Wolfgang; Okitolonda, Emile; Hensley, Lisa E.; Lloyd-Smith, James O.; Smith, Thomas B.; Rimoin, Anne W.

    2013-01-01

    Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4th Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts. PMID:23935820

  2. Pathogen-host associations and predicted range shifts of human monkeypox in response to climate change in central Africa.

    Science.gov (United States)

    Thomassen, Henri A; Fuller, Trevon; Asefi-Najafabady, Salvi; Shiplacoff, Julia A G; Mulembakani, Prime M; Blumberg, Seth; Johnston, Sara C; Kisalu, Neville K; Kinkela, Timothée L; Fair, Joseph N; Wolfe, Nathan D; Shongo, Robert L; LeBreton, Matthew; Meyer, Hermann; Wright, Linda L; Muyembe, Jean-Jacques; Buermann, Wolfgang; Okitolonda, Emile; Hensley, Lisa E; Lloyd-Smith, James O; Smith, Thomas B; Rimoin, Anne W

    2013-01-01

    Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th) Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.

  3. Pathogen-host associations and predicted range shifts of human monkeypox in response to climate change in central Africa.

    Directory of Open Access Journals (Sweden)

    Henri A Thomassen

    Full Text Available Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV, an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX. Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC, and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.

  4. Mycobacterium bovis: A Model Pathogen at the Interface of Livestock, Wildlife, and Humans

    Directory of Open Access Journals (Sweden)

    Mitchell V. Palmer

    2012-01-01

    Full Text Available Complex and dynamic interactions involving domestic animals, wildlife, and humans create environments favorable to the emergence of new diseases, or reemergence of diseases in new host species. Today, reservoirs of Mycobacterium bovis, the causative agent of tuberculosis in animals, and sometimes humans, exist in a range of countries and wild animal populations. Free-ranging populations of white-tailed deer in the US, brushtail possum in New Zealand, badger in the Republic of Ireland and the United Kingdom, and wild boar in Spain exemplify established reservoirs of M. bovis. Establishment of these reservoirs is the result of factors such as spillover from livestock, translocation of wildlife, supplemental feeding of wildlife, and wildlife population densities beyond normal habitat carrying capacities. As many countries attempt to eradicate M. bovis from livestock, efforts are impeded by spillback from wildlife reservoirs. It will not be possible to eradicate this important zoonosis from livestock unless transmission between wildlife and domestic animals is halted. Such an endeavor will require a collaborative effort between agricultural, wildlife, environmental, and political interests.

  5. Survey on the Ability of Wolbachia to Control Human Viral, Protozoan, and Filarial Disease Pathogens

    Directory of Open Access Journals (Sweden)

    Garedaghi Yagoob

    2014-04-01

    Full Text Available Objective: Most human filarial nematode parasites and arthropods are hosts for a bacterial endosymbiont, Wolbachia. In filariasis, Wolbachia are required for normal development, fertility, and survival. However, in arthropods, Wolbachia are largely parasitic and can influence development and reproduction, but are generally not required for host survival. Materials and Methods: Due to their obligate nature in filarial parasites, Wolbachia have been a target for drug discovery initiatives using several approaches including diversity and focused library screening and genomic sequence analysis. Results: In vitro and in vivo anti-Wolbachia antibiotic treatments have been shown to have adulticidal activity, a long sought goal of filarial parasite drug discovery. In mosquitoes, it has been shown that the presence of Wolbachia can inhibit the transmission of certain viruses, such as dengue, chikungunya, yellow fever, West Nile, as well as the infectivity of the malaria-causing protozoan, Plasmodium and filarial nematodes. Conclusion: Wolbachia can cause a form of conditional sterility that can be used to suppress populations of mosquitoes and additional medically important insects. Thus, Wolbachia, a pandemic endosymbiont, offers great potential for elimination of a wide-variety of devastating human diseases.

  6. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest.

    Science.gov (United States)

    Hagen, Ferry; Ceresini, Paulo C; Polacheck, Itzhack; Ma, Hansong; van Nieuwerburgh, Filip; Gabaldón, Toni; Kagan, Sarah; Pursall, E Rhiannon; Hoogveld, Hans L; van Iersel, Leo J J; Klau, Gunnar W; Kelk, Steven M; Stougie, Leen; Bartlett, Karen H; Voelz, Kerstin; Pryszcz, Leszek P; Castañeda, Elizabeth; Lazera, Marcia; Meyer, Wieland; Deforce, Dieter; Meis, Jacques F; May, Robin C; Klaassen, Corné H W; Boekhout, Teun

    2013-01-01

    Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.

  7. Microevolution of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Humans, Egypt, 2007–2011

    Science.gov (United States)

    Younan, Mary; Poh, Mee Kian; Elassal, Emad; Davis, Todd; Rivailler, Pierre; Balish, Amanda L.; Simpson, Natosha; Jones, Joyce; Deyde, Varough; Loughlin, Rosette; Perry, Ije; Gubareva, Larisa; ElBadry, Maha A.; Truelove, Shaun; Gaynor, Anne M.; Mohareb, Emad; Amin, Magdy; Cornelius, Claire; Pimentel, Guillermo; Earhart, Kenneth; Naguib, Amel; Abdelghani, Ahmed S.; Refaey, Samir; Klimov, Alexander I.; Kandeel, Amr

    2013-01-01

    We analyzed highly pathogenic avian influenza A(H5N1) viruses isolated from humans infected in Egypt during 2007–2011. All analyzed viruses evolved from the lineage of subtype H5N1 viruses introduced into Egypt in 2006; we found minimal evidence of reassortment and no exotic introductions. The hemagglutinin genes of the viruses from 2011 formed a monophyletic group within clade 2.2.1 that also included human viruses from 2009 and 2010 and contemporary viruses from poultry; this finding is consistent with zoonotic transmission. Although molecular markers suggestive of decreased susceptibility to antiviral drugs were detected sporadically in the neuraminidase and matrix 2 proteins, functional neuraminidase inhibition assays did not identify resistant viruses. No other mutations suggesting a change in the threat to public health were detected in the viral proteomes. However, a comparison of representative subtype H5N1 viruses from 2011 with older subtype H5N1 viruses from Egypt revealed substantial antigenic drift. PMID:23260983

  8. Gold nanoparticles synthesized by Brassica oleracea (Broccoli) acting as antimicrobial agents against human pathogenic bacteria and fungi

    Science.gov (United States)

    Piruthiviraj, Prakash; Margret, Anita; Krishnamurthy, Poornima Priyadharsani

    2016-04-01

    Production of antimicrobial agents through the synthesis of gold nanoparticles using green technology has been extensively made consistent by various researchers; yet, this study uses the flower bud's aqueous extracts of Brassica oleracea (Broccoli) as a reducing agent for chloroauric acid (1 mM). After 30 min of incubation, synthesis of gold nanoparticles (AuNps) was observed by a change in extract color from pale yellow to purple color. Synthesis of AuNps was confirmed in UV-visible spectroscopy at the range of approximately 560 nm. The SEM analysis showed the average nanoparticles size of 12-22 nm. The antimicrobial activity of AuNps was analyzed by subjecting it to human pathogenic bacteria (Gram-positive Staphylococcus aureus and Gram-negative Klebsiella pneumonia) and fungi (Aspergillus flavus, Aspergillus niger and Candida albicans) using disc diffusion method. The broccoli-synthesized AuNps showed the efficient antibacterial and antifungal activity of above-mentioned microbes. It was confirmed that AuNps have the best antimicrobial agent compared to the standard antibiotics (Gentamicin and Fluconazole). When the concentrations of AuNps were increased (10, 25, and 50 µg/ml), the sensitivity zone also increased for all the tested microbes. The synthesized AuNps are capable of rendering high antimicrobial efficacy and, hence, have a great potential in the preparation of drugs used against major bacterial and fungal diseases in humans.

  9. The Rho-activating CNF1 toxin from pathogenic E. coli: A risk factor for human cancer development?

    Directory of Open Access Journals (Sweden)

    Fiorentini Carla

    2008-03-01

    Full Text Available Abstract Nowadays, there is increasing evidence that some pathogenic bacteria can contribute to specific stages of cancer development. The concept that bacterial infection could be involved in carcinogenesis acquired a widespread interest with the discovery that H. pylori is able to establish chronic infections in the stomach and that this infection is associated with an increased risk of gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Chronic infections triggered by bacteria can facilitate tumor initiation or progression since, during the course of infection, normal cell functions can come under the control of pathogen factors that directly manipulate the host regulatory pathways and the inflammatory reactions. Renowned publications have recently corroborated the molecular mechanisms that link bacterial infections, inflammation and cancer, indicating certain strains of Escherichia coli as a risk factor for patients with colon cancer. E. coli is a normal inhabitant of the human intestine that becomes highly pathogenic following the acquisition of virulence factors, including a protein toxin named cytotoxic necrotizing factor 1 (CNF1. This toxin permanently activates the small GTP-binding proteins belonging to the Rho family, thus promoting a prominent polymerization of the actin cytoskeleton as well as a number of cellular responses, including changes in protein expression and functional modification of the cell physiology. CNF1 is receiving an increasing attention as a putative factor involved in transformation because of its ability to: (i induce COX2 expression, an immediate-early gene over-expressed in some type of cancers; (ii induce a long-lasting activation of the transcription factor NF-kB, a largely accepted marker of tumor cells; (iii protect epithelial cells from apoptosis; (iv ensue the release of pro-inflammatory cytokines in epithelial and endothelial cells; and (v promote cellular motility. As cancer may

  10. Molecular evidence for recent founder populations and human-mediated migration in the barley scald pathogen Rhynchosporium secalis.

    Science.gov (United States)

    Linde, C C; Zala, M; McDonald, B A

    2009-06-01

    Rhynchosporium secalis is an important pathogen of barley globally. Fourteen polymorphic microsatellites were analyzed for 1664 R. secalis isolates sampled from 37 field populations to infer their demographic history. The results falsified the hypothesis that R. secalis co-evolved with its barley host in the Middle East. Populations from Scandinavia had significantly higher allelic diversities, the greatest number of private alleles and the highest genotypic diversities. All but three of the analyzed populations had an excess of gene diversity compared to the number of alleles, consistent with a recent population bottleneck. The remaining populations had a gene diversity deficit consistent with a population expansion following a recent population bottleneck in the last +/-100 years. A coalescent analysis revealed that the effective population sizes based on theta, of the analyzed populations were small relative to their ancestral population sizes, indicating that only a fraction of the diversity present in the ancestral populations was transmitted into current populations. These findings are consistent with the hypothesis that the pathogen population on barley experienced a selection bottleneck imposed by the host and/or are founder populations. The mean estimate of migration rates was 2.2 (avg 90% confidence interval=1.3-3.1). Major migration routes were identified among populations separated by long distances, eg between South Africa and Australia, as well as among North Africa, the Middle East and California, suggesting contemporary exchange of infected barley seed. In contrast with earlier findings, most populations exhibited significant gametic disequilibrium, probably as a result of genetic drift. We conclude that the majority of R. secalis populations have experienced human-mediated migration that led to numerous and relatively recent founder events around the world.

  11. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

    Science.gov (United States)

    Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

    2016-11-01

    With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Common and specific genomic sequences of avian and human extraintestinal pathogenic Escherichia coli as determined by genomic subtractive hybridization

    Directory of Open Access Journals (Sweden)

    Nolan Lisa K

    2007-08-01

    Full Text Available Abstract Background Suppression subtractive hybridization (SSH strategy was used with extraintestinal pathogenic Escherichia coli (EXPEC that cause avian colibacillosis (avian pathogenic E. coli or APEC and human urinary tract infections (uropathogenic E. coli or UPEC to determine if they possessed genes that were host and/or niche specific. Both APEC and UPEC isolates were used as tester and driver strains in 4 different SSHs in order to obtain APEC- and UPEC-specific subtraction fragments (SFs. Results These procedures yielded a total of 136 tester-specific SFs of which 85 were APEC-derived and 51 were UPEC-derived. Most of the APEC-derived SFs were associated with plasmids; whereas, the majority of UPEC-derived sequences matched to the bacterial chromosome. We further determined the distribution of these tester-derived sequences in a collection of UPEC and APEC isolates using polymerase chain reaction techniques. Plasmid-borne, APEC-derived sequences (tsh, cvaB, traR, traC and sopB were predominantly present in APEC, as compared to UPEC. Of the UPEC-derived SFs, those encoding hemolysin D and F1C major and minor fimbrial subunits were present only in UPEC. However, two UPEC-derived SFs that showed strong similarity to the uropathgenic-specific protein gene (usp occurred in APEC, demonstrating that usp is not specific to UPEC. Conclusion This study provides evidence of the genetic variability of ExPEC as well as genomic similarities between UPEC and APEC; it did not identify any single marker that would dictate host and/or niche specificity in APEC or UPEC. However, further studies on the genes that encode putative or hypothetical proteins might offer important insight into the pathogenesis of disease, as caused by these two ExPEC.

  13. The Black Yeast Exophiala dermatitidis and Other Selected Opportunistic Human Fungal Pathogens Spread from Dishwashers to Kitchens.

    Directory of Open Access Journals (Sweden)

    Jerneja Zupančič

    Full Text Available We investigated the diversity and distribution of fungi in nine different sites inside 30 residential dishwashers. In total, 503 fungal strains were isolated, which belong to 10 genera and 84 species. Irrespective of the sampled site, 83% of the dishwashers were positive for fungi. The most frequent opportunistic pathogenic species were Exophiala dermatitidis, Candida parapsilosis sensu stricto, Exophiala phaeomuriformis, Fusarium dimerum, and the Saprochaete/Magnusiomyces clade. The black yeast E. dermatitidis was detected in 47% of the dishwashers, primarily at the dishwasher rubber seals, at up to 106 CFU/cm2; the other fungi detected were in the range of 102 to 105 CFU/cm2. The other most heavily contaminated dishwasher sites were side nozzles, doors and drains. Only F. dimerum was isolated from washed dishes, while dishwasher waste water contained E. dermatitidis, Exophiala oligosperma and Sarocladium killiense. Plumbing systems supplying water to household appliances represent the most probable route for contamination of dishwashers, as the fungi that represented the core dishwasher mycobiota were also detected in the tap water. Hot aerosols from dishwashers contained the human opportunistic yeast C. parapsilosis, Rhodotorula mucilaginosa and E. dermatitidis (as well as common air-borne genera such as Aspergillus, Penicillium, Trichoderma and Cladosporium. Comparison of fungal contamination of kitchens without and with dishwashers revealed that virtually all were contaminated with fungi. In both cases, the most contaminated sites were the kitchen drain and the dish drying rack. The most important difference was higher prevalence of black yeasts (E. dermatitidis in particular in kitchens with dishwashers. In kitchens without dishwashers, C. parapsilosis strongly prevailed with negligible occurrence of E. dermatitidis. F. dimerum was isolated only from kitchens with dishwashers, while Saprochaete/Magnusiomyces isolates were only found within

  14. Foodborne pathogens

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    Thomas Bintsis

    2017-06-01

    Full Text Available Foodborne pathogens are causing a great number of diseases with significant effects on human health and economy. The characteristics of the most common pathogenic bacteria (Bacillus cereus, Campylobacter jejuni, Clostridium botulinum, Clostridium perfringens, Cronobacter sakazakii, Esherichia coli, Listeria monocytogenes, Salmonella spp., Shigella spp., Staphylococccus aureus, Vibrio spp. and Yersinia enterocolitica, viruses (Hepatitis A and Noroviruses and parasites (Cyclospora cayetanensis, Toxoplasma gondii and Trichinella spiralis, together with some important outbreaks, are reviewed. Food safety management systems based on to classical hazard-based approach has been proved to be inefficient, and risk-based food safety approach is now suggested from leading researchers and organizations. In this context, a food safety management system should be designed in a way to estimate the risks to human health from food consumption and to identify, select and implement mitigation strategies in order to control and reduce these risks. In addition, the application of suitable food safety education programs for all involved people in the production and consumption of foods is suggested.

  15. Chlamydia trachomatis and Genital Mycoplasmas: Pathogens with an Impact on Human Reproductive Health

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    Sunčanica Ljubin-Sternak

    2014-01-01

    Full Text Available The most prevalent, curable sexually important diseases are those caused by Chlamydia trachomatis (C. trachomatis and genital mycoplasmas. An important characteristic of these infections is their ability to cause long-term sequels in upper genital tract, thus potentially affecting the reproductive health in both sexes. Pelvic inflammatory disease (PID, tubal factor infertility (TFI, and ectopic pregnancy (EP are well documented complications of C. trachomatis infection in women. The role of genital mycoplasmas in development of PID, TFI, and EP requires further evaluation, but growing evidence supports a significant role for these in the pathogenesis of chorioamnionitis, premature membrane rupture, and preterm labor in pregnant woman. Both C. trachomatis and genital mycoplasmas can affect the quality of sperm and possibly influence the fertility of men. For the purpose of this paper, basic, epidemiologic, clinical, therapeutic, and public health issue of these infections were reviewed and discussed, focusing on their impact on human reproductive health.

  16. Gene Function Analysis in the Ubiquitous Human Commensal and Pathogen Malassezia Genus

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    Giuseppe Ianiri

    2016-11-01

    Full Text Available The genus Malassezia includes 14 species that are found on the skin of humans and animals and are associated with a number of diseases. Recent genome sequencing projects have defined the gene content of all 14 species; however, to date, genetic manipulation has not been possible for any species within this genus. Here, we develop and then optimize molecular tools for the transformation of Malassezia furfur and Malassezia sympodialis using Agrobacterium tumefaciens delivery of transfer DNA (T-DNA molecules. These T-DNAs can insert randomly into the genome. In the case of M. furfur, targeted gene replacements were also achieved via homologous recombination, enabling deletion of the ADE2 gene for purine biosynthesis and of the LAC2 gene predicted to be involved in melanin biosynthesis. Hence, the introduction of exogenous DNA and direct gene manipulation are feasible in Malassezia species.

  17. Occurrence and antimicrobial resistance of pathogenic Escherichia coli and Salmonella spp. in retail raw table eggs sold for human consumption in Enugu state, Nigeria

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    O. Josephine Okorie-Kanu

    2016-11-01

    Full Text Available Aim: This study was conducted to investigate the occurrence of pathogenic Escherichia coli and Salmonella species in retail raw table eggs sold for human consumption in Enugu State and to determine the resistance of these pathogens to antimicrobials commonly used in human and veterinary practices in Nigeria. Materials and Methods: A total of 340 raw table eggs comprising 68 composite samples (5 eggs per composite sample were collected from five selected farms (13 composite samples from the farms and 10 retail outlets (55 composite samples from the retail outlets in the study area over a period of 4-month (March-June, 2014. The eggs were screened for pathogenic E. coli and Salmonella species following standard procedures within 24 h of sample collection. Isolates obtained were subjected to in-vitro antimicrobial susceptibility test with 15 commonly used antimicrobials using the disk diffusion method. Results: About 37 (54.4% and 7 (10.3% of the 68 composite samples were positive for pathogenic E. coli and Salmonella species, respectively. The shells showed significantly higher (p0.05. The organisms obtained showed a multiple drug resistance. They were completely resistant to nitrofurantoin, sulfamethoxazole/ trimethoprim, penicillin G and oxacillin. In addition to these, Salmonella spp. also showed 100% resistance to tetracycline. The pathogenic E. coli isolates obtained were 100% susceptible to gentamicin, neomycin, ciprofloxacin, and amoxicillin-clavulanic acid while Salmonella spp. showed 100% susceptibility to erythromycin, neomycin, and rifampicin. Both organisms showed varying degrees of resistance to streptomycin, amoxicillin, vancomycin, and doxycycline. Conclusion: From the results of the study, it can be concluded that the raw table eggs marketed for human consumption in Enugu State, Nigeria is contaminated with pathogenic E. coli and Salmonella species that showed multiple drug resistance to antimicrobial agents commonly used in

  18. Occurrence and antimicrobial resistance of pathogenicEscherichia coliandSalmonellaspp. in retail raw table eggs sold for human consumption in Enugu state, Nigeria.

    Science.gov (United States)

    Okorie-Kanu, O Josephine; Ezenduka, E Vivienne; Okorie-Kanu, C Onwuchokwe; Ugwu, L Chinweokwu; Nnamani, U John

    2016-11-01

    This study was conducted to investigate the occurrence of pathogenic Escherichia coli and Salmonella species in retail raw table eggs sold for human consumption in Enugu State and to determine the resistance of these pathogens to antimicrobials commonly used in human and veterinary practices in Nigeria. A total of 340 raw table eggs comprising 68 composite samples (5 eggs per composite sample) were collected from five selected farms (13 composite samples from the farms) and 10 retail outlets (55 composite samples from the retail outlets) in the study area over a period of 4-month (March-June, 2014). The eggs were screened for pathogenic E. coli and Salmonella species following standard procedures within 24 h of sample collection. Isolates obtained were subjected to in-vitro antimicrobial susceptibility test with 15 commonly used antimicrobials using the disk diffusion method. About 37 (54.4%) and 7 (10.3%) of the 68 composite samples were positive for pathogenic E. coli and Salmonella species, respectively. The shells showed significantly higher (pE. coli than eggs from the retail outlets while the reverse was the case for Salmonella species even though they were not significant (p>0.05). The organisms obtained showed a multiple drug resistance. They were completely resistant to nitrofurantoin, sulfamethoxazole/trimethoprim, penicillin G and oxacillin. In addition to these, Salmonella spp. also showed 100% resistance to tetracycline. The pathogenic E. coli isolates obtained were 100% susceptible to gentamicin, neomycin, ciprofloxacin, and amoxicillin-clavulanic acid while Salmonella spp. showed 100% susceptibility to erythromycin, neomycin, and rifampicin. Both organisms showed varying degrees of resistance to streptomycin, amoxicillin, vancomycin, and doxycycline. From the results of the study, it can be concluded that the raw table eggs marketed for human consumption in Enugu State, Nigeria is contaminated with pathogenic E. coli and Salmonella species that

  19. Quantification of Salmonella Survival and Infection in an In vitro Model of the Human Intestinal Tract as Proxy for Foodborne Pathogens.

    NARCIS (Netherlands)

    Wijnands, Lucas M; Teunis, Peter F M; Kuijpers, Angelina F A; Delfgou-Van Asch, Ellen H M; Pielaat, Annemarie

    2017-01-01

    Different techniques are available for assessing differences in virulence of bacterial foodborne pathogens. The use of animal models or human volunteers is not expedient for various reasons; the use of epidemiological data is often hampered by lack of crucial data. In this paper, we describe a

  20. Sporothrix chilensis sp. nov. (Ascomycota : Ophiostomatales), a soil-borne agent of human sporotrichosis with mild-pathogenic potential to mammals

    NARCIS (Netherlands)

    Rodrigues, Anderson Messias; Cruz Choappa, Rodrigo; Fernandes, Geisa Ferreira; de Hoog, G Sybren; de Camargo, Zoilo Pires

    A combination of phylogeny, evolution, morphologies and ecologies has enabled major advances in understanding the taxonomy of Sporothrix species, including members exhibiting distinct lifestyles such as saprobes, human/animal pathogens, and insect symbionts. Phylogenetic analyses of ITS1/2 + 5.8s

  1. 7 CFR 28.414 - Strict Low Middling Light Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... CONTAINER REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Standards Light Spotted Cotton § 28.414 Strict Low Middling Light Spotted Color. Strict Low Middling Light Spotted Color is color which in spot or...

  2. A network of paralogous stress response transcription factors in the human pathogen Candida glabrata.

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    Jawad eMerhej

    2016-05-01

    Full Text Available The yeast Candida glabrata has become the second cause of systemic candidemia in humans. However, relatively few genome-wide studies have been conducted in this organism and our knowledge of its transcriptional regulatory network is quite limited. In the present work, we combined genome-wide chromatin immunoprecipitation (ChIP-seq, transcriptome analyses and DNA binding motif predictions to describe the regulatory interactions of the seven Yap (Yeast AP1 transcription factors of C. glabrata. We described a transcriptional network containing 255 regulatory interactions and 309 potential target genes. We predicted with high confidence the preferred DNA binding sites for 5 of the 7 CgYaps and showed a strong conservation of the Yap DNA binding properties between S. cerevisiae and C. glabrata. We provided reliable functional annotation for 3 of the 7 Yaps and identified for Yap1 and Yap5 a core regulon which is conserved in S. cerevisiae, C. glabrata and C. albicans. We uncovered new roles for CgYap7 in the regulation of iron-sulfur cluster biogenesis, for CgYap1 in the regulation of heme biosynthesis and for CgYap5 in the repression of GRX4 in response to iron starvation. These transcription factors define an interconnected transcriptional network at the cross-roads between redox homeostasis, oxygen consumption and iron metabolism.

  3. Structural Insights into Inhibition of Sterol 14[alpha]-Demethylase in the Human Pathogen Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Lepesheva, Galina I.; Hargrove, Tatiana Y.; Anderson, Spencer; Kleshchenko, Yuliya; Furtak, Vyacheslav; Wawrzak, Zdzislaw; Villalta, Fernando; Waterman, Michael R. (Vanderbilt); (NWU); (Meharry)

    2010-09-02

    Trypanosoma cruzi causes Chagas disease (American trypanosomiasis), which threatens the lives of millions of people and remains incurable in its chronic stage. The antifungal drug posaconazole that blocks sterol biosynthesis in the parasite is the only compound entering clinical trials for the chronic form of this infection. Crystal structures of the drug target enzyme, Trypanosoma cruzi sterol 14{alpha}-demethylase (CYP51), complexed with posaconazole, another antifungal agent fluconazole and an experimental inhibitor, (R)-4{prime}-chloro-N-(1-(2,4-dichlorophenyl)-2-(1H-imid-azol-1-yl)ethyl)biphenyl-4-carboxamide (VNF), allow prediction of important chemical features that enhance the drug potencies. Combined with comparative analysis of inhibitor binding parameters, influence on the catalytic activity of the trypanosomal enzyme and its human counterpart, and their cellular effects at different stages of the Trypanosoma cruzi life cycle, the structural data provide a molecular background to CYP51 inhibition and azole resistance and enlighten the path for directed design of new, more potent and selective drugs to develop an efficient treatment for Chagas disease.

  4. Global profiling of lysine acetylation in human histoplasmosis pathogen Histoplasma capsulatum.

    Science.gov (United States)

    Xie, Longxiang; Fang, Wenjie; Deng, Wanyan; Yu, Zhaoxiao; Li, Juan; Chen, Min; Liao, Wanqing; Xie, Jianping; Pan, Weihua

    2016-04-01

    Histoplasma capsulatum is the causative agent of human histoplasmosis, which can cause respiratory and systemic mycosis in immune-compromised individuals. Lysine acetylation, a protein posttranslational protein modification, is widespread in both eukaryotes and prokaryotes. Although increasing evidence suggests that lysine acetylation may play critical roles in fungus physiology, very little is known about its extent and function in H. capsulatum. To comprehensively profile protein lysine acetylation in H. capsulatum, we performed a global acetylome analysis through peptide prefractionation, antibody enrichment, and LC-MS/MS analysis, identifying 775 acetylation sites on 456 acetylated proteins; and functionally analysis showing their involvement in different biological processes. We defined six types of acetylation site motifs, and the results imply that lysine residue of polypeptide with tyrosine at the -1 and +1 positions, histidine at the +1 position, and phenylalanine (F) at the +1 and +2 position is a preferred substrate of lysine acetyltransferase. Moreover, some virulence factors candidates including calmodulin and DnaK are acetylated. In conclusion, our data set may serve as an important resource for the elucidation of associations between functional protein lysine acetylation and virulence in H. capsulatum. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Targeting Toxoplasma Tubules: Tubulin, Microtubules, and Associated Proteins in a Human Pathogen

    Science.gov (United States)

    2014-01-01

    Toxoplasma gondii is an obligate intracellular parasite that causes serious opportunistic infections, birth defects, and blindness in humans. Microtubules are critically important components of diverse structures that are used throughout the Toxoplasma life cycle. As in other eukaryotes, spindle microtubules are required for chromosome segregation during replication. Additionally, a set of membrane-associated microtubules is essential for the elongated shape of invasive “zoites,” and motility follows a spiral trajectory that reflects the path of these microtubules. Toxoplasma zoites also construct an intricate, tubulin-based apical structure, termed the conoid, which is important for host cell invasion and associates with proteins typically found in the flagellar apparatus. Last, microgametes specifically construct a microtubule-containing flagellar axoneme in order to fertilize macrogametes, permitting genetic recombination. The specialized roles of these microtubule populations are mediated by distinct sets of associated proteins. This review summarizes our current understanding of the role of tubulin, microtubule populations, and associated proteins in Toxoplasma; these components are used for both novel and broadly conserved processes that are essential for parasite survival. PMID:25380753

  6. Quantification of Salmonella Survival and Infection in an In vitro Model of the Human Intestinal Tract as Proxy for Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Lucas M. Wijnands

    2017-06-01

    Full Text Available Different techniques are available for assessing differences in virulence of bacterial foodborne pathogens. The use of animal models or human volunteers is not expedient for various reasons; the use of epidemiological data is often hampered by lack of crucial data. In this paper, we describe a static, sequential gastrointestinal tract (GIT model system in which foodborne pathogens are exposed to simulated gastric and intestinal contents of the human digestive tract, including the interaction of pathogens with the intestinal epithelium. The system can be employed with any foodborne bacterial pathogens. Five strains of Salmonella Heidelberg and one strain of Salmonella Typhimurium were used to assess the robustness of the system. Four S. Heidelberg strains originated from an outbreak, the fifth S. Heidelberg strain and the S. Typhimurium strain originated from routine meat inspections. Data from plate counts, collected for determining the numbers of surviving bacteria in each stage, were used to quantify both the experimental uncertainty and biological variability of pathogen survival throughout the system. For this, a hierarchical Bayesian framework using Markov chain Monte Carlo (MCMC was employed. The model system is able to distinguish serovars/strains for in vitro infectivity when accounting for within strain biological variability and experimental uncertainty.

  7. Emerging Threats for Human Health in Poland: Pathogenic Isolates from Drug Resistant Acanthamoeba Keratitis Monitored in terms of Their In Vitro Dynamics and Temperature Adaptability.

    Science.gov (United States)

    Chomicz, Lidia; Conn, David Bruce; Padzik, Marcin; Szaflik, Jacek P; Walochnik, Julia; Zawadzki, Paweł J; Pawłowski, Witold; Dybicz, Monika

    2015-01-01

    Amphizoic amoebae generate a serious human health threat due to their pathogenic potential as facultative parasites, causative agents of vision-threatening Acanthamoeba keratitis (AK). Recently, AK incidences have been reported with increasing frequency worldwide, particularly in contact lens wearers. In our study, severe cases of AK in Poland and respective pathogenic isolates were assessed at clinical, morphological, and molecular levels. Misdiagnoses and the unsuccessful treatment in other ophthalmic units delayed suitable therapy, and resistance to applied chemicals resulted in severe courses and treatment difficulties. Molecular assessment indicated that all sequenced pathogenic corneal isolates deriving from Polish patients with AK examined by us showed 98-100% homology with Acanthamoeba genotype T4, the most prevalent genotype in this human ocular infection worldwide. In vitro assays revealed that the pathogenic strains are able to grow at elevated temperature and have a wide adaptive capability. This study is our subsequent in vitro investigation on pathogenic Acanthamoeba strains of AK originating from Polish patients. Further investigations designed to foster a better understanding of the factors leading to an increase of AK observed in the past years in Poland may help to prevent or at least better cope with future cases.

  8. Emerging Threats for Human Health in Poland: Pathogenic Isolates from Drug Resistant Acanthamoeba Keratitis Monitored in terms of Their In Vitro Dynamics and Temperature Adaptability

    Directory of Open Access Journals (Sweden)

    Lidia Chomicz

    2015-01-01

    Full Text Available Amphizoic amoebae generate a serious human health threat due to their pathogenic potential as facultative parasites, causative agents of vision-threatening Acanthamoeba keratitis (AK. Recently, AK incidences have been reported with increasing frequency worldwide, particularly in contact lens wearers. In our study, severe cases of AK in Poland and respective pathogenic isolates were assessed at clinical, morphological, and molecular levels. Misdiagnoses and the unsuccessful treatment in other ophthalmic units delayed suitable therapy, and resistance to applied chemicals resulted in severe courses and treatment difficulties. Molecular assessment indicated that all sequenced pathogenic corneal isolates deriving from Polish patients with AK examined by us showed 98–100% homology with Acanthamoeba genotype T4, the most prevalent genotype in this human ocular infection worldwide. In vitro assays revealed that the pathogenic strains are able to grow at elevated temperature and have a wide adaptive capability. This study is our subsequent in vitro investigation on pathogenic Acanthamoeba strains of AK originating from Polish patients. Further investigations designed to foster a better understanding of the factors leading to an increase of AK observed in the past years in Poland may help to prevent or at least better cope with future cases.

  9. Emerging Threats for Human Health in Poland: Pathogenic Isolates from Drug Resistant Acanthamoeba Keratitis Monitored in terms of Their In Vitro Dynamics and Temperature Adaptability

    Science.gov (United States)

    Chomicz, Lidia; Conn, David Bruce; Padzik, Marcin; Szaflik, Jacek P.; Walochnik, Julia; Zawadzki, Paweł J.; Pawłowski, Witold; Dybicz, Monika

    2015-01-01

    Amphizoic amoebae generate a serious human health threat due to their pathogenic potential as facultative parasites, causative agents of vision-threatening Acanthamoeba keratitis (AK). Recently, AK incidences have been reported with increasing frequency worldwide, particularly in contact lens wearers. In our study, severe cases of AK in Poland and respective pathogenic isolates were assessed at clinical, morphological, and molecular levels. Misdiagnoses and the unsuccessful treatment in other ophthalmic units delayed suitable therapy, and resistance to applied chemicals resulted in severe courses and treatment difficulties. Molecular assessment indicated that all sequenced pathogenic corneal isolates deriving from Polish patients with AK examined by us showed 98–100% homology with Acanthamoeba genotype T4, the most prevalent genotype in this human ocular infection worldwide. In vitro assays revealed that the pathogenic strains are able to grow at elevated temperature and have a wide adaptive capability. This study is our subsequent in vitro investigation on pathogenic Acanthamoeba strains of AK originating from Polish patients. Further investigations designed to foster a better understanding of the factors leading to an increase of AK observed in the past years in Poland may help to prevent or at least better cope with future cases. PMID:26682216

  10. On N. Chomsky’s strict subcategorization of verbs

    Directory of Open Access Journals (Sweden)

    Janez Orešnik

    1966-12-01

    Full Text Available This paper studies the so-called strict subcategorization rules, and the theory associated with them, in the transformational grammar of. Erigl·ish as proposed by Noarn Chomsky in his Aspects. The syntactic component of English transformational grammar consists of two mutually ordered parts, viz., the base and the transformational subcomponents. The initial part of the base are the so-called categorial rules, which are of almost exclusive interest to us here. Their primary task is to generate what are usually called basic sentence patterns, and will here, with Chomsky (Aspects, p.ll3, be designated with the expression, frames of category symbols.- The rules of the transformational subcomponent modify, in various ways, the frames generated by the base. For several reasons - one of them being that the correct work of the transformational subcomponent quite often depends on the kind of lexical items with which the syntactic positions in the frames of category symbols have been filled, the lexical items must be introduced from the lexicon into the empty positions in the frames before the rules of the transformational subcomponent can be allowed to modify the frames.

  11. Managing Hanford Site solid waste through strict acceptance criteria

    International Nuclear Information System (INIS)

    Jasen, W.G.; Pierce, R.D.; Willis, N.P.

    1993-02-01

    Various types of waste have been generated during the 50-year history of the Hanford Site. Regulatory changes in the last 20 years have provided the emphasis for better management of these wastes. Interpretations of the Atomic Energy Act of 1954 (AEA) and the Resource Conservation and Recovery Act of 1976 (RCRA) have led to the definition of a group of wastes called radioactive mixed wastes (RMW). As a result of the radioactive and hazardous properties of these wastes, strict management programs have been implemented for the management of these wastes. Solid waste management is accomplished through a systems performance approach to waste management that used best-demonstrated available technology (BDAT) and best management practices. The solid waste program at the Hanford Site strives to integrate all aspects of management relative to the treatment, storage and disposal (TSD) of solid waste. Often there are many competing and important needs. It is a difficult task to balance these needs in a manner that is both equitable and productive. Management science is used to help the process of making decisions. Tools used to support the decision making process include five-year planning, cost estimating, resource allocation, performance assessment, waste volume forecasts, input/output models, and waste acceptance criteria. The purpose of this document is to describe how one of these tools, waste acceptance criteria, has helped the Hanford Site manage solid wastes

  12. Effects of strict prolonged bed rest on cardiorespiratory fitness

    DEFF Research Database (Denmark)

    Ried-Larsen, Mathias; Aarts, Hugo M; Joyner, Michael J

    2017-01-01

    with larger declines in V̇o2max). Furthermore, the systematic review revealed a gap in the knowledge about the cardiovascular response to extreme physical inactivity, particularly in older subjects and women of any age group. In addition to its relevance to spaceflight, this lack of data has significant....... Since 1949, 80 studies with a total of 949 participants (>90% men) have been published with data on strict bed rest and V̇o2max The studies were conducted mainly in young participants [median age (interquartile range) 24.5 (22.4-34.0) yr]. The duration of bed rest ranged from 1 to 90 days. V̇o2max...... declined linearly across bed rest duration. No statistical difference in the decline among studies reporting V̇o2max as l/min (-0.3% per day) compared with studies reporting V̇o2max normalized to body weight (ml·kg-1·min-1; -0.43% per day) was observed. Although both total body weight and lean body mass...

  13. Fixed point iterations for strictly hemi-contractive maps in uniformly smooth Banach spaces

    International Nuclear Information System (INIS)

    Chidume, C.E.; Osilike, M.O.

    1993-05-01

    It is proved that the Mann iteration process converges strongly to the fixed point of a strictly hemi-contractive map in real uniformly smooth Banach spaces. The class of strictly hemi-contractive maps includes all strictly pseudo-contractive maps with nonempty fixed point sets. A related result deals with the Ishikawa iteration scheme when the mapping is Lipschitzian and strictly hemi-contractive. Our theorems generalize important known results. (author). 29 refs

  14. Cathepsin B-like and cell death in the unicellular human pathogen Leishmania.

    Science.gov (United States)

    El-Fadili, A K; Zangger, H; Desponds, C; Gonzalez, I J; Zalila, H; Schaff, C; Ives, A; Masina, S; Mottram, J C; Fasel, N

    2010-09-02

    In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H(2)O(2)), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes.

  15. Plants promote mating and dispersal of the human pathogenic fungus Cryptococcus.

    Science.gov (United States)

    Springer, Deborah J; Mohan, Rajinikanth; Heitman, Joseph

    2017-01-01

    Infections due to Cryptococcus are a leading cause of fungal infections worldwide and are acquired as a result of environmental exposure to desiccated yeast or spores. The ability of Cryptococcus to grow, mate, and produce infectious propagules in association with plants is important for the maintenance of the genetic diversity and virulence factors important for infection of animals and humans. In the Western United States and Canada, Cryptococcus has been associated with conifers and tree species other than Eucalyptus; however, to date Cryptococcus has only been studied on live Arabidopsis thaliana, Eucalyptus sp., and Terminalia catappa (almond) seedlings. Previous research has demonstrated the ability of Cryptococcus to colonize live plants, leaves, and vasculature. We investigated the ability of Cryptococcus to grow on live seedlings of the angiosperms, A. thaliana, Eucalyptus camaldulensis, Colophospermum mopane, and the gymnosperms, Pseudotsuga menziesii (Douglas fir), and Tsuga heterophylla (Western hemlock). We observed a broad-range ability of Cryptococcus to colonize both traditional infection models as well as newly tested conifer species. Furthermore, C. neoformans, C. deneoformans, C. gattii (VGI), C. deuterogattii (VGII) and C. bacillisporus (VGIII) were able to colonize live plant leaves and needles but also undergo filamentation and mating on agar seeded with plant materials or in saprobic association with dead plant materials. The ability of Cryptococcus to grow and undergo filamentation and reproduction in saprobic association with both angiosperms and gymnosperms highlights an important role of plant debris in the sexual cycle and exposure to infectious propagules. This study highlights the broad importance of plants (and plant debris) as the ecological niche and reservoirs of infectious propagules of Cryptococcus in the environment.

  16. The Human Milk Protein-Lipid Complex HAMLET Sensitizes Bacterial Pathogens to Traditional Antimicrobial Agents

    Science.gov (United States)

    Marks, Laura R.; Clementi, Emily A.; Hakansson, Anders P.

    2012-01-01

    The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend

  17. Plants promote mating and dispersal of the human pathogenic fungus Cryptococcus.

    Directory of Open Access Journals (Sweden)

    Deborah J Springer

    Full Text Available Infections due to Cryptococcus are a leading cause of fungal infections worldwide and are acquired as a result of environmental exposure to desiccated yeast or spores. The ability of Cryptococcus to grow, mate, and produce infectious propagules in association with plants is important for the maintenance of the genetic diversity and virulence factors important for infection of animals and humans. In the Western United States and Canada, Cryptococcus has been associated with conifers and tree species other than Eucalyptus; however, to date Cryptococcus has only been studied on live Arabidopsis thaliana, Eucalyptus sp., and Terminalia catappa (almond seedlings. Previous research has demonstrated the ability of Cryptococcus to colonize live plants, leaves, and vasculature. We investigated the ability of Cryptococcus to grow on live seedlings of the angiosperms, A. thaliana, Eucalyptus camaldulensis, Colophospermum mopane, and the gymnosperms, Pseudotsuga menziesii (Douglas fir, and Tsuga heterophylla (Western hemlock. We observed a broad-range ability of Cryptococcus to colonize both traditional infection models as well as newly tested conifer species. Furthermore, C. neoformans, C. deneoformans, C. gattii (VGI, C. deuterogattii (VGII and C. bacillisporus (VGIII were able to colonize live plant leaves and needles but also undergo filamentation and mating on agar seeded with plant materials or in saprobic association with dead plant materials. The ability of Cryptococcus to grow and undergo filamentation and reproduction in saprobic association with both angiosperms and gymnosperms highlights an important role of plant debris in the sexual cycle and exposure to infectious propagules. This study highlights the broad importance of plants (and plant debris as the ecological niche and reservoirs of infectious propagules of Cryptococcus in the environment.

  18. Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones.

    Science.gov (United States)

    Yu, Run; Chen, Chun-Rong; Liu, Xiaohong; Kodra, János T

    2012-10-01

    We have previously demonstrated that a homozygous inactivating P86S mutation of the glucagon receptor (GCGR) causes a novel human disease of hyperglucagonemia, pancreatic α-cell hyperplasia, and pancreatic neuroendocrine tumors (Mahvash disease). The mechanisms for the decreased activity of the P86S mutant (P86S) are abnormal receptor localization to the endoplasmic reticulum (ER) and defective interaction with glucagon. To search for targeted therapies for Mahvash disease, we examined whether P86S can be trafficked to the plasma membrane by pharmacological chaperones and whether novel glucagon analogs restore effective receptor interaction. We used enhanced green fluorescent protein-tagged P86S stably expressed in HEK 293 cells to allow fluorescence imaging and western blotting and molecular modeling to design novel glucagon analogs in which alanine 19 was replaced with serine or asparagine. Incubation at 27 °C largely restored normal plasma membrane localization and normal processing of P86S but osmotic chaperones had no effects. The ER stressors thapsigargin and curcumin partially rescued P86S. The lipophilic GCGR antagonist L-168,049 also partially rescued P86S, so did Cpd 13 and 15 to a smaller degree. The rescued P86S led to more glucagon-stimulated cAMP production and was internalized by glucagon. Compared with the native glucagon, the novel glucagon analogs failed to stimulate more cAMP production by P86S. We conclude that the mutant GCGR is partially rescued by several pharmacological chaperones and our data provide proof-of-principle evidence that Mahvash disease can be potentially treated with pharmacological chaperones. The novel glucagon analogs, however, failed to interact with P86S more effectively.

  19. Highly Pathogenic Avian Influenza H5N6 Viruses Exhibit Enhanced Affinity for Human Type Sialic Acid Receptor and In-Contact Transmission in Model Ferrets.

    Science.gov (United States)

    Sun, Honglei; Pu, Juan; Wei, Yandi; Sun, Yipeng; Hu, Jiao; Liu, Litao; Xu, Guanlong; Gao, Weihua; Li, Chong; Zhang, Xuxiao; Huang, Yinhua; Chang, Kin-Chow; Liu, Xiufan; Liu, Jinhua

    2016-07-15

    Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SAα2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans. Extended epizootics and panzootics of H5N1 viruses have led to the emergence of the novel 2.3.4.4 clade of H5 virus subtypes, including H5N2, H5N6, and H5N8 reassortants. Avian H5N6 viruses from this clade have caused three fatalities out of six severe human infections in China since the first case in 2014. However, the biological properties of this subtype, especially the pathogenicity and transmission in mammals, are not known. Here, we found that natural avian H5N6 viruses have acquired a high affinity for human-type virus receptor. Compared to the parental clade 2.3.4 H5N1 virus, emergent H5N6 isolates showed less severe pathogenicity in mice and ferrets but acquired efficient in-contact transmission in ferrets. These findings suggest that the threat of avian H5N6 viruses to humans should not be ignored. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Human rhinovirus infections in rural Thailand: epidemiological evidence for rhinovirus as both pathogen and bystander.

    Directory of Open Access Journals (Sweden)

    Alicia M Fry

    Full Text Available BACKGROUND: We describe human rhinovirus (HRV detections in SaKaeo province, Thailand. METHODS: From September 1, 2003-August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. RESULTS: HRVs were detected in 315 (16% of 1919 hospitalized patients and 27 (9.6% of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1-4 year: 29%, ≥ 65 years: 9%; controls: <1 year: 24%, 1-4 year: 14%, ≥ 65 years: 2.8%. Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year, 1-4 years (457, and ≥ 65 years (71. All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61% and all adult age groups. HRV-C was the most common species in the 1-4 year (51% and 5-19 year age groups (54%. Compared to controls, hospitalized adults (≥ 19 years and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5 or HVR-C (OR 2.7, CI: 1.2, 5.9 detection. CONCLUSIONS: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species, and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.

  1. Novel Sampling Method for Assessing Human-Pathogen Interactions in the Natural Environment Using Boot Socks and Citizen Scientists, with Application to Campylobacter Seasonality.

    Science.gov (United States)

    Jones, Natalia R; Millman, Caroline; van der Es, Mike; Hukelova, Miroslava; Forbes, Ken J; Glover, Catherine; Haldenby, Sam; Hunter, Paul R; Jackson, Kathryn; O'Brien, Sarah J; Rigby, Dan; Strachan, Norval J C; Williams, Nicola; Lake, Iain R

    2017-07-15

    This paper introduces a novel method for sampling pathogens in natural environments. It uses fabric boot socks worn over walkers' shoes to allow the collection of composite samples over large areas. Wide-area sampling is better suited to studies focusing on human exposure to pathogens (e.g., recreational walking). This sampling method is implemented using a citizen science approach: groups of three walkers wearing boot socks undertook one of six routes, 40 times over 16 months in the North West (NW) and East Anglian (EA) regions of England. To validate this methodology, we report the successful implementation of this citizen science approach, the observation that Campylobacter bacteria were detected on 47% of boot socks, and the observation that multiple boot socks from individual walks produced consistent results. The findings indicate higher Campylobacter levels in the livestock-dominated NW than in EA (55.8% versus 38.6%). Seasonal differences in the presence of Campylobacter bacteria were found between the regions, with indications of winter peaks in both regions but a spring peak in the NW. The presence of Campylobacter bacteria on boot socks was negatively associated with ambient temperature ( P = 0.011) and positively associated with precipitation ( P Campylobacter survival and the probability of material adhering to boot socks. Campylobacter jejuni was the predominant species found; Campylobacter coli was largely restricted to the livestock-dominated NW. Source attribution analysis indicated that the potential source of C. jejuni was predominantly sheep in the NW and wild birds in EA but did not differ between peak and nonpeak periods of human incidence. IMPORTANCE There is debate in the literature on the pathways through which pathogens are transferred from the environment to humans. We report on the success of a novel method for sampling human-pathogen interactions using boot socks and citizen science techniques, which enable us to sample human-pathogen

  2. Diallylthiosulfinate (Allicin, a Volatile Antimicrobial from Garlic (Allium sativum, Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor

    Directory of Open Access Journals (Sweden)

    Jana Reiter

    2017-10-01

    Full Text Available Garlic (Allium sativum has potent antimicrobial activity due to allicin (diallylthiosulfinate synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR strains, was demonstrated. Minimal inhibitory (MIC and minimal bactericidal concentrations (MBC were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH. Similarly, the sensitivity of rat precision-cut lung slices (PCLS to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  3. Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor.

    Science.gov (United States)

    Reiter, Jana; Levina, Natalja; van der Linden, Mark; Gruhlke, Martin; Martin, Christian; Slusarenko, Alan J

    2017-10-12

    Garlic ( Allium sativum ) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H₂O₂ using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas , Streptococcus , and Staphylococcus , including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.

  4. A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2

    Energy Technology Data Exchange (ETDEWEB)

    Thiele, Ines; Hyduke, Daniel R.; Steeb, Benjamin; Fankam, Guy; Allen, Douglas K.; Bazzani, Susanna; Charusanti, Pep; Chen, Feng-Chi; Fleming, Ronan MT; Hsiung, Chao A.; De Keersmaecker, Sigrid CJ; Liao, Yu-Chieh; Marchal, Kathleen; Mo, Monica L.; Özdemir, Emre; Raghunathan, Anu; Reed, Jennifer L.; Shin, Sook-Il; Sigurbjörnsdóttir, Sara; Steinmann, Jonas; Sudarsan, Suresh; Swainston, Neil; Thijs, Inge M.; Zengler, Karsten; Palsson, Bernhard O.; Adkins, Joshua N.; Bumann, Dirk

    2011-01-01

    Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem. Here, we describe a community-driven effort, in which more than 20 experts in S. Typhimurium biology and systems biology collaborated to reconcile and expand the S. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for S. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches. Finally, taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.

  5. Characterization of an Hfq dependent antisense sRNA in the Gram-positive human pathogen Listeria monocytogenes

    DEFF Research Database (Denmark)

    Nielsen, Jesper Sejrup; Lei Kristensen, Lisbeth; Hanghøj Chrisitansen, Mie

    between sRNA and target mRNA rely on the RNA chaperone Hfq. Hfq is a ubiquitous protein found in almost all genres of bacterial life. However, so far its role as an RNA chaperone has only been described in Gram-negative species such as Escherichia coli and Salmonella (Vogel, J. 2009). We previously....... A large proportion of regulatory sRNAs function through an antisense based mechanism in which they bind to trans-encoded target mRNAs in or near the ribosomal binding site thereby affecting translation of one or more target mRNAs (Aiba H. 2007). In most of the cases studied so far, the in vivo interaction...... identified several Hfq-binding sRNAs in the Gram-positive human pathogen L. monocytogenes (Christiansen et al 2006). Through bioinformatics, we have identified a number of candidate targets for one of these sRNAs (LhrA). Here, we present the characterization of one of these targets. Our results suggest...

  6. Proteome data from a host-pathogen interaction study with Staphylococcus aureus and human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Kristin Surmann

    2016-06-01

    Full Text Available To simultaneously obtain proteome data of host and pathogen from an internalization experiment, human alveolar epithelial A549 cells were infected with Staphylococcus aureus HG001 which carried a plasmid (pMV158GFP encoding a continuously expressed green fluorescent protein (GFP. Samples were taken hourly between 1.5 h and 6.5 h post infection. By fluorescence activated cell sorting GFP-expressing bacteria could be enriched from host cell debris, but also infected host cells could be separated from those which did not carry bacteria after contact (exposed. Additionally, proteome data of A549 cells which were not exposed to S. aureus but underwent the same sample processing steps are provided as a control. Time-resolved changes in bacterial protein abundance were quantified in a label-free approach. Proteome adaptations of host cells were monitored by comparative analysis to a stable isotope labeled cell culture (SILAC standard. Proteins were extracted from the cells, digested proteolytically, measured by nanoLC–MS/MS, and subsequently identified by database search and then quantified. The data presented here are related to a previously published research article describing the interplay of S. aureus HG001 and human epithelial cells (Surmann et al., 2015 [1]. They have been deposited to the ProteomeXchange platform with the identifiers PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD002384 for the S. aureus HG001 proteome dataset and PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD002388 for the A549 proteome dataset.

  7. Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Ismail Nahed

    2012-05-01

    Full Text Available Abstract Background Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human monocytic ehrlichiosis (HME that mimic toxic shock-like syndrome. Murine studies indicate that over activation of cellular immunity followed by immune suppression plays a central role in mediating tissue injury and organ failure during fatal HME. However, there are no human studies that examine the correlates of resistance or susceptibility to severe and fatal HME. Results In this study, we compared the immune responses in two patients with mild/non fatal and severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver enzymes. The levels of different immunological factors in the blood of those patients were examined and compared to healthy controls. Our data showed that fatal HME is associated with defective production of Th1 cytokines such as ( IFNγ and IL-2, increased anti-inflammatory (IL-10 and IL-13 and pro-inflammatory (TNF-α, IL-1α, IL-1β, and IL-6 cytokines, increased levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP-1α, MIP-1β, but not RANTES and IP-10, increased levels of neutrophils chemokine and growth factor (IL-8 and G-CSF, and elevated expression of tumor necrosis factor receptor (TNFR, and toll like receptors 2 and 4 compared to patients with non fatal HME and healthy controls. Conclusions Fatal Ehrlichia-induced toxic shock is associated with defective Th1 responses, possible immune suppression mediated by IL-10. In addition, marked leukopenia observed in patients with fatal disease could be attributed to enhanced apoptosis of leukocytes and/or elevated chemokine production that could promote migration of immune cells to sites of infection causing tissue injury.

  8. Strict or graduated punishment? Effect of punishment strictness on the evolution of cooperation in continuous public goods games.

    Directory of Open Access Journals (Sweden)

    Hajime Shimao

    Full Text Available Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher's threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player's death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results.

  9. Strict or Graduated Punishment? Effect of Punishment Strictness on the Evolution of Cooperation in Continuous Public Goods Games

    Science.gov (United States)

    Shimao, Hajime; Nakamaru, Mayuko

    2013-01-01

    Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher’s threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player’s death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results. PMID:23555826

  10. Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection

    Science.gov (United States)

    Roberts, Gareth W.; Heuston, Sinéad; Brown, Amanda C.; Chess, James A.; Toleman, Mark A.; Gahan, Cormac G. M.; Hill, Colin; Parish, Tanya; Williams, John D.; Davies, Simon J.; Johnson, David W.; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

    2011-01-01

    Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early

  11. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Steen-Jensen, Daniel Bisgaard; Laursen, Janne Marie

    2012-01-01

    of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella...... spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria...... provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella...

  12. Clonal complex 398 methicillin susceptible Staphylococcus aureus: a frequent unspecialized human pathogen with specific phenotypic and genotypic characteristics.

    Directory of Open Access Journals (Sweden)

    Tomasz Chroboczek

    Full Text Available Clonal complex 398 livestok-associated-MRSA (CC398 LA-MRSA clone is described as a major animal pathogen that can also colonize and infect humans. CC398 methicillin susceptible Staphylococcus aureus (CC398 MSSA is less described. We identified 126 CC398 MSSA strains of human origin within 6380 S. aureus isolates gathered between 2009 and 2011, from the French National Reference Centre for Staphylococci. They were characterized using antimicrobial susceptibility testing, spa typing, DNA microarrays (Identibac S. aureus Genotyping ®, Alere, CC398-specific sequence PCR, ermT (encoding macrolides résistance PCR. Fifty-three CC398 LA-MRSA collected from French pigs and veal were used as comparators, and phylogenetic relations between human CC398 MSSA and animal CC398 MRSA populations were explored on the basis of spa-typing and DNA microarrays. CC398 MSSA were able to induce a large spectrum of infections (especially skin, bloodstream, and pneumonias. The prevalence rate of this clone was high in MSSA population, i.e., 24.7% in a local prospective study on nasal colonization, and 7.5% in a national prospective study on infective endocarditis. CC398 MSSA isolates were frequently (89% erythromycin resistant, due to the presence of the ermT gene, a gene not detected in erythromycin resistant CC398 LA-MRSA strains. Expression of staphylococcal complement inhibitor (scn and the chemotaxis inhibitory protein (chp, was also specific to this population. The CC398 MRSA signature included also a panel of antibiotic resistance genes, especially a type IV or V cassette mec and tetM. CC398 MSSA and CC398 LA-MRSA populations were closely related based on spa-typing and DNA microarrays, with the MRSA strains forming the most derived lineage in phylogenic trees. Both MSSA and MRSA populations may come from common ancestors, which would have evolved in the settings of different selective pressures, explaining the acquisition of ermT, chp and scn for MSSA, and

  13. Rabbit monoclonal antibodies directed at the T3SS effector protein YopM identify human pathogenic Yersinia isolates.

    Science.gov (United States)

    Rüter, Christian; Silva, Mariana Ruiz; Grabowski, Benjamin; Lubos, Marie-Luise; Scharnert, Julia; Poceva, Marija; von Tils, Dominik; Flieger, Antje; Heesemann, Jürgen; Bliska, James B; Schmidt, M Alexander

    2014-05-01

    The Yersinia outer protein M (YopM) is a type 3 secretion system (T3SS)-dependent effector protein of Yersinia enterocolitica, Yersinia pseudotuberculosis and Yersinia pestis. Although YopM is indispensable for full virulence, its molecular functions still remain largely elusive. Recently, we could identify the recombinant YopM (rYopM) protein derived from the Y. enterocolitica strain 8081 (JB580) as a cell-penetrating protein, which down-regulates the expression of various pro-inflammatory cytokines including TNFα. In this study, we have generated rabbit monoclonal anti-YopM antibodies (RabMabs). RabMabs were characterized by SDS-PAGE and Western blotting using various truncated versions of rYopM to identify epitope-containing domains. RabMabs recognizing either the N- or C-terminus of YopM were characterized further and validated using a collection of 61 pathogenic and non-pathogenic Yersinia strains as well as exemplary strains of major intestinal bacterial pathogens such as Salmonella enterica ssp. enterica, Shigella flexneri and intestinal pathogenic Escherichia coli. RabMab 41.3 directed at the N-terminus of YopM of Y. enterocolitica strain 8081 recognized all YopM-expressing pathogenic Yersinia strains analyzed in this study but failed to recognize non-pathogenic isolates. Thus, RabMab 41.3 might be applicable for the detection of pathogenic Yersinia strains. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Sediment composition influences spatial variation in the abundance of human pathogen indicator bacteria within an estuarine environment.

    Science.gov (United States)

    Perkins, Tracy L; Clements, Katie; Baas, Jaco H; Jago, Colin F; Jones, Davey L; Malham, Shelagh K; McDonald, James E

    2014-01-01

    Faecal contamination of estuarine and coastal waters can pose a risk to human health, particularly in areas used for shellfish production or recreation. Routine microbiological water quality testing highlights areas of faecal indicator bacteria (FIB) contamination within the water column, but fails to consider the abundance of FIB in sediments, which under certain hydrodynamic conditions can become resuspended. Sediments can enhance the survival of FIB in estuarine environments, but the influence of sediment composition on the ecology and abundance of FIB is poorly understood. To determine the relationship between sediment composition (grain size and organic matter) and the abundance of pathogen indicator bacteria (PIB), sediments were collected from four transverse transects of the Conwy estuary, UK. The abundance of culturable Escherichia coli, total coliforms, enterococci, Campylobacter, Salmonella and Vibrio spp. in sediments was determined in relation to sediment grain size, organic matter content, salinity, depth and temperature. Sediments that contained higher proportions of silt and/or clay and associated organic matter content showed significant positive correlations with the abundance of PIB. Furthermore, the abundance of each bacterial group was positively correlated with the presence of all other groups enumerated. Campylobacter spp. were not isolated from estuarine sediments. Comparisons of the number of culturable E. coli, total coliforms and Vibrio spp. in sediments and the water column revealed that their abundance was 281, 433 and 58-fold greater in sediments (colony forming units (CFU)/100g) when compared with the water column (CFU/100ml), respectively. These data provide important insights into sediment compositions that promote the abundance of PIB in estuarine environments, with important implications for the modelling and prediction of public health risk based on sediment resuspension and transport.

  15. General aspects concerning strictly meat and fish transmitted parasitic infections

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2012-03-01

    Full Text Available All helminths parasitosis transmitted to humans trough ingestion of infested fleshes, where man is definitive host too, are represented by four groups of helminths: the cestodes Dyphyllobothrium spp and Spirometra spp. (Sparganum proliferum is the name of the immature plerocercoid larva, the trematodes Opisthorchis Clonorchis “group” (many could be the genera and species involved, and the nematode Capillaria philippinensis. So, for fishes humans foods (fresh or salted water the control and prevention in veterinary health must be directed to investigation regarding intermediate stages of these parasites in fishes for human alimentation; if present, they must be eliminated. The helminths parasitosis transmitted to humans trough ingestion of infected mammals meats, are represented by taeniasis (Taenia saginata, T. solium and T. saginata asiatica, where man id definitive host and the infection is caused by ingestion of bovine or swine meat, containing larvae of these cestodes, and by trichinellosis, where humans represent a intermediate stage, and the eventual pathology is caused as by adult (acute infection as by larvae (chronic infection of this nematode: usually the meats responsible are infected pork, wild pork or horse (Trichinella spp. Is inside the meats of these animals. So the veterinary control and prophylaxis are necessary to avoid this disease and preventing the infection that could be severe.

  16. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population

    NARCIS (Netherlands)

    Köck, R; Werner, P; Friedrich, A W; Fegeler, C; Becker, K

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878

  17. Adhesion of Human Probiotic Lactobacillus rhamnosus to Cervical and Vaginal Cells and Interaction with Vaginosis-Associated Pathogens

    Directory of Open Access Journals (Sweden)

    Sophie Coudeyras

    2008-01-01

    Full Text Available Objectives. The ability of a probiotic Lactobacillus rhamnosus strain (Lcr35 to adhere to cervical and vaginal cells and to affect the viability of two main vaginosis-associated pathogens, Prevotella bivia, Gardnerella vaginalis, as well as Candida albicans was investigated. Methods. Adhesion ability was determined in vitro with immortalized epithelial cells from the endocervix, ectocervix, and vagina. Coculture experiments were performed to count viable pathogens cells in the presence of Lcr35. Results. Lcr35 was able to specifically and rapidly adhere to the three cell lines. In coculture assays, a decrease in pathogen cell division rate was observed as from 4 hours of incubation and bactericidal activity after a longer period of incubation, mostly with P. bivia. Conclusion. The ability of Lcr35 to adhere to cervicovaginal cells and its antagonist activities against vaginosis-associated pathogens suggest that this probiotic strain is a promising candidate for use in therapy.

  18. Purification, crystallization and diffraction studies of the methyltransferases BT-2972 and BVU-3255 from antibiotic-resistant pathogens of the genus Bacteroides from the human intestine

    International Nuclear Information System (INIS)

    Kumar, Veerendra; Mallika, Nagarajan; Sivaraman, J.

    2011-01-01

    The expression, purification, crystallization and diffraction of two methyltransferases BT-2972 and BVU-3255 from two Bacteroides species of antibiotic-resistant pathogens from the human intestine are reported. The methyltransferases BT-2972 and BVU-3255 from two different Bacteroides species that are antibiotic-resistant pathogens from the human intestine were cloned, overexpressed and purified, yielding approximately 120 mg of each protein from 1 l culture. Apo BT-2972 and BVU-3255 and their complexes with S-adenosylmethionine or S-adenosylhomocysteine were crystallized in four different crystal forms using the hanging-drop vapour-diffusion method. These crystals diffracted to resolutions ranging from 2.8 to 2.2 Å. Sequence analysis suggested that the two proteins are homologous small-molecule methyltransferases

  19. Tigecycline Susceptibility of Klebsiella pneumoniae Complex and Escherichia coli Isolates from Companion Animals: The Prevalence of Tigecycline-Nonsusceptible K. pneumoniae Complex, Including Internationally Expanding Human Pathogenic Lineages.

    Science.gov (United States)

    Sato, Toyotaka; Harada, Kazuki; Usui, Masaru; Tsuyuki, Yuzo; Shiraishi, Tsukasa; Tamura, Yutaka; Yokota, Shin-Ichi

    2017-12-12

    Transmission of tigecycline-nonsusceptible pathogenic Enterobacteriaceae from companion animals to human should be a concern because tigecycline is a last-line drug for treating multidrug-resistant Enterobacteriaceae in human medicine. However, tigecycline susceptibility of Enterobacteriaceae isolated from companion animals has not been investigated. In this study, we investigated the tigecycline susceptibility of Klebsiella pneumoniae complex and Escherichia coli isolates from dogs and cats, and evaluated their human pathogenicity potential. Tigecycline susceptibility of K. pneumoniae, including Klebsiella quasipneumoniae (n = 86) and E. coli (n = 100) strains isolated from dogs and cats was investigated. The antimicrobial susceptibility, capsular serotype, multilocus sequence type, ompK36 group, presence of virulence genes, and serum resistance of tigecycline-nonsusceptible isolates were evaluated. All E. coli isolates were susceptible to tigecycline. Two K. pneumoniae (minimum inhibitory concentration [MIC], 4 mg/L) and one K. quasipneumoniae (MIC, 8 mg/L) isolates were tigecycline resistant. Sixteen K. pneumoniae and one K. quasipneumoniae isolates were tigecycline intermediate (2 mg/L). All tigecycline-nonsusceptible isolates (n = 20) were also ciprofloxacin nonsusceptible. These isolates harbored five to nine virulence genes; 16 isolates were resistant to the human serum. In addition, STs of 13 K. pneumoniae isolates were reported to be found in strains isolated from human; isolates considered high-risk clones in human (ST11, ST15, and ST147) were also identified. In conclusion, the isolation of tigecycline-nonsusceptible K. pneumoniae from companion animals is an impact from the viewpoint of One Health approach to antimicrobial resistance that companion animals are a reservoir of human pathogenic lineages.

  20. Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus

    OpenAIRE

    Sobel Leonard, Ashley; Weissman, Daniel B.; Greenbaum, Benjamin; Ghedin, Elodie; Koelle, Katia

    2017-01-01

    ABSTRACT The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmis...