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Sample records for morphogenetic fungal virulence

  1. Plasma membrane lipids and their role in fungal virulence.

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    Rella, Antonella; Farnoud, Amir M; Del Poeta, Maurizio

    2016-01-01

    There has been considerable evidence in recent years suggesting that plasma membrane lipids are important regulators of fungal pathogenicity. Various glycolipids have been shown to impart virulent properties in several fungal species, while others have been shown to play a role in host defense. In addition to their role as virulence factors, lipids also contribute to other virulence mechanisms such as drug resistance, biofilm formation, and release of extracellular vesicles. In addition, lipids also affect the mechanical properties of the plasma membrane through the formation of packed microdomains composed mainly of sphingolipids and sterols. Changes in the composition of lipid microdomains have been shown to disrupt the localization of virulence factors and affect fungal pathogenicity. This review gathers evidence on the various roles of plasma membrane lipids in fungal virulence and how lipids might contribute to the different processes that occur during infection and treatment. Insight into the role of lipids in fungal virulence can lead to an improved understanding of the process of fungal pathogenesis and the development of new lipid-mediated therapeutic strategies. Published by Elsevier Ltd.

  2. Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

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    Cecilia Li

    2016-09-01

    Full Text Available Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK, which are involved in synthesizing inositol polyphosphates (IP. We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P and pyrophosphate (PP groups covalently attached at different positions. This review focuses on (1 the characterization of the Plc1/IPK pathway in C. neoformans; (2 the identification of PP-IP5 (IP7 as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3 why IPK enzymes represent suitable candidates for drug development.

  3. Role of Arf GTPases in fungal morphogenesis and virulence.

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    Hayet Labbaoui

    2017-02-01

    Full Text Available Virulence of the human fungal pathogen Candida albicans depends on the switch from budding to filamentous growth, which requires sustained membrane traffic and polarized growth. In many organisms, small GTPases of the Arf (ADP-ribosylation factor family regulate membrane/protein trafficking, yet little is known about their role in fungal filamentous growth. To investigate these GTPases in C. albicans, we generated loss of function mutants in all 3 Arf proteins, Arf1-Arf3, and 2 Arf-like proteins, Arl1 and Arl3. Our results indicate that of these proteins, Arf2 is required for viability and sensitivity to antifungal drugs. Repressible ARF2 expression results in defects in filamentous growth, cell wall integrity and virulence, likely due to alteration of the Golgi. Arl1 is also required for invasive filamentous growth and, although arl1/arl1 cells can initiate hyphal growth, hyphae are substantially shorter than that of the wild-type, due to the inability of this mutant to maintain hyphal growth at a single site. We show that this defect does not result from an alteration of phospholipid distribution and is unlikely to result from the sole Golgin Imh1 mislocalization, as Imh1 is not required for invasive filamentous growth. Rather, our results suggest that the arl1/arl1 hyphal growth defect results from increased secretion in this mutant. Strikingly, the arl1/arl1 mutant is drastically reduced in virulence during oropharyngeal candidiasis. Together, our results highlight the importance of Arl1 and Arf2 as key regulators of hyphal growth and virulence in C. albicans and identify a unique function of Arl1 in secretion.

  4. Xylose donor transport is critical for fungal virulence.

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    Lucy X Li

    2018-01-01

    Full Text Available Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading cause of fungal meningitis worldwide and is responsible for hundreds of thousands of deaths annually. Cryptococcal glycans are required for fungal survival in the host and for pathogenesis. Most glycans are made in the secretory pathway, although the activated precursors for their synthesis, nucleotide sugars, are made primarily in the cytosol. Nucleotide sugar transporters are membrane proteins that solve this topological problem, by exchanging nucleotide sugars for the corresponding nucleoside phosphates. The major virulence factor of C. neoformans is an anti-phagocytic polysaccharide capsule that is displayed on the cell surface; capsule polysaccharides are also shed from the cell and impede the host immune response. Xylose, a neutral monosaccharide that is absent from model yeast, is a significant capsule component. Here we show that Uxt1 and Uxt2 are both transporters specific for the xylose donor, UDP-xylose, although they exhibit distinct subcellular localization, expression patterns, and kinetic parameters. Both proteins also transport the galactofuranose donor, UDP-galactofuranose. We further show that Uxt1 and Uxt2 are required for xylose incorporation into capsule and protein; they are also necessary for C. neoformans to cause disease in mice, although surprisingly not for fungal viability in the context of infection. These findings provide a starting point for deciphering the substrate specificity of an important class of transporters, elucidate a synthetic pathway that may be productively targeted for therapy, and contribute to our understanding of fundamental glycobiology.

  5. Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

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    Hee-Soo Park

    2016-09-01

    Full Text Available Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substrates. Herein, we identified and characterized calcineurin substrates in C. neoformans by employing phosphoproteomic TiO2 enrichment and quantitative mass spectrometry. The identified targets include the transactivator Crz1 as well as novel substrates whose functions are linked to P-bodies/stress granules (PBs/SGs and mRNA translation and decay, such as Pbp1 and Puf4. We show that Crz1 is a bona fide calcineurin substrate, and Crz1 localization and transcriptional activity are controlled by calcineurin. We previously demonstrated that thermal and other stresses trigger calcineurin localization to PBs/SGs. Several calcineurin targets localized to PBs/SGs, including Puf4 and Pbp1, contribute to stress resistance and virulence individually or in conjunction with Crz1. Moreover, Pbp1 is also required for sexual development. Genetic epistasis analysis revealed that Crz1 and the novel targets Lhp1, Puf4, and Pbp1 function in a branched calcineurin pathway that orchestrates stress survival and virulence. These findings support a model whereby calcineurin controls stress and virulence, at the transcriptional level via Crz1, and post-transcriptionally by localizing to PBs/SGs and acting on targets involved in mRNA metabolism. The calcineurin targets identified in this study share little overlap with known calcineurin substrates, with the exception of Crz1. In particular, the mRNA binding proteins and PBs/SGs residents comprise a cohort of novel calcineurin targets that have not been previously linked to calcineurin in mammals or in Saccharomyces cerevisiae. This study suggests either extensive evolutionary rewiring of the calcineurin pathway, or alternatively that these novel calcineurin targets have yet

  6. Correlates of virulence in a frog-killing fungal pathogen: evidence from a California amphibian decline

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    Jonah Piovia-Scott; Karen Pope; S. Joy Worth; Erica Bree Rosenblum; Dean Simon; Gordon Warburton; Louise A. Rollins-Smith; Laura K. Reinert; Heather L. Wells; Dan Rejmanek; Sharon Lawler; Janet Foley

    2015-01-01

    The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused declines and extinctions in amphibians worldwide, and there is increasing evidence that some strains of this pathogen are more virulent than others. While a number of putative virulence factors have been identified, few studies link these factors to specific epizootic events. We...

  7. Protein kinase A and fungal virulence: a sinister side to a conserved nutrient sensing pathway.

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    Fuller, Kevin K; Rhodes, Judith C

    2012-01-01

    Diverse fungal species are the cause of devastating agricultural and human diseases. As successful pathogenesis is dependent upon the ability of the fungus to adapt to the nutritional and chemical environment of the host, the understanding of signaling pathways required for such adaptation will provide insights into the virulence of these pathogens and the potential identification of novel targets for antifungal intervention. The cAMP-PKA signaling pathway is well conserved across eukaryotes. In the nonpathogenic yeast, S. cerevisiae, PKA is activated in response to extracellular nutrients and subsequently regulates metabolism and growth. Importantly, this pathway is also a regulator of pathogenesis, as defects in PKA signaling lead to an attenuation of virulence in diverse plant and human pathogenic fungi. This review will compare and contrast PKA signaling in S. cerevisiae vs. various pathogenic species and provide a framework for the role of this pathway in regulating fungal virulence.

  8. Cotton plants export microRNAs to inhibit virulence gene expression in a fungal pathogen.

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    Zhang, Tao; Zhao, Yun-Long; Zhao, Jian-Hua; Wang, Sheng; Jin, Yun; Chen, Zhong-Qi; Fang, Yuan-Yuan; Hua, Chen-Lei; Ding, Shou-Wei; Guo, Hui-Shan

    2016-09-26

    Plant pathogenic fungi represent the largest group of disease-causing agents on crop plants, and are a constant and major threat to agriculture worldwide. Recent studies have shown that engineered production of RNA interference (RNAi)-inducing dsRNA in host plants can trigger specific fungal gene silencing and confer resistance to fungal pathogens 1-7 . Although these findings illustrate efficient uptake of host RNAi triggers by pathogenic fungi, it is unknown whether or not such an uptake mechanism has been evolved for a natural biological function in fungus-host interactions. Here, we show that in response to infection with Verticillium dahliae (a vascular fungal pathogen responsible for devastating wilt diseases in many crops) cotton plants increase production of microRNA 166 (miR166) and miR159 and export both to the fungal hyphae for specific silencing. We found that two V. dahliae genes encoding a Ca 2+ -dependent cysteine protease (Clp-1) and an isotrichodermin C-15 hydroxylase (HiC-15), and targeted by miR166 and miR159, respectively, are both essential for fungal virulence. Notably, V. dahliae strains expressing either Clp-1 or HiC-15 rendered resistant to the respective miRNA exhibited drastically enhanced virulence in cotton plants. Together, our findings identify a novel defence strategy of host plants by exporting specific miRNAs to induce cross-kingdom gene silencing in pathogenic fungi and confer disease resistance.

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

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    Douglas, Lois M; Konopka, James B

    2016-03-01

    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.

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

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    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

  11. Genetic diversity, virulence and fitness evolution in an obligate fungal parasite of bees.

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    Evison, S E F; Foley, K; Jensen, A B; Hughes, W O H

    2015-01-01

    Within-host competition is predicted to drive the evolution of virulence in parasites, but the precise outcomes of such interactions are often unpredictable due to many factors including the biology of the host and the parasite, stochastic events and co-evolutionary interactions. Here, we use a serial passage experiment (SPE) with three strains of a heterothallic fungal parasite (Ascosphaera apis) of the Honey bee (Apis mellifera) to assess how evolving under increasing competitive pressure affects parasite virulence and fitness evolution. The results show an increase in virulence after successive generations of selection and consequently faster production of spores. This faster sporulation, however, did not translate into more spores being produced during this longer window of sporulation; rather, it appeared to induce a loss of fitness in terms of total spore production. There was no evidence to suggest that a greater diversity of competing strains was a driver of this increased virulence and subsequent fitness cost, but rather that strain-specific competitive interactions influenced the evolutionary outcomes of mixed infections. It is possible that the parasite may have evolved to avoid competition with multiple strains because of its heterothallic mode of reproduction, which highlights the importance of understanding parasite biology when predicting disease dynamics. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  12. Correlates of virulence in a frog-killing fungal pathogen: evidence from a California amphibian decline.

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    Piovia-Scott, Jonah; Pope, Karen; Worth, S Joy; Rosenblum, Erica Bree; Poorten, Thomas; Refsnider, Jeanine; Rollins-Smith, Louise A; Reinert, Laura K; Wells, Heather L; Rejmanek, Dan; Lawler, Sharon; Foley, Janet

    2015-07-01

    The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused declines and extinctions in amphibians worldwide, and there is increasing evidence that some strains of this pathogen are more virulent than others. While a number of putative virulence factors have been identified, few studies link these factors to specific epizootic events. We documented a dramatic decline in juvenile frogs in a Bd-infected population of Cascades frogs (Rana cascadae) in the mountains of northern California and used a laboratory experiment to show that Bd isolated in the midst of this decline induced higher mortality than Bd isolated from a more stable population of the same species of frog. This highly virulent Bd isolate was more toxic to immune cells and attained higher density in liquid culture than comparable isolates. Genomic analyses revealed that this isolate is nested within the global panzootic lineage and exhibited unusual genomic patterns, including increased copy numbers of many chromosomal segments. This study integrates data from multiple sources to suggest specific phenotypic and genomic characteristics of the pathogen that may be linked to disease-related declines.

  13. Forging the ring: from fungal septins' divergent roles in morphology, septation and virulence to factors contributing to their assembly into higher order structures.

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    Vargas-Muñiz, Jose M; Juvvadi, Praveen R; Steinbach, William J

    2016-09-01

    Septins are a conserved family of GTP-binding proteins that are distributed across different lineages of the eukaryotes, with the exception of plants. Septins perform a myriad of functions in fungal cells, ranging from controlling morphogenetic events to contributing to host tissue invasion and virulence. One key attribute of the septins is their ability to assemble into heterooligomeric complexes that organizse into higher order structures. In addition to the established role of septins in the model budding yeast, Saccharomyces cerevisiae, their importance in other fungi recently emerges. While newer roles for septins are being uncovered in these fungi, the mechanism of how septins assemble into a complex and their regulation is only beginning to be comprehended. In this review, we summarize recent findings on the role of septins in different fungi and focus on how the septin complexes of different fungi are organized in vitro and in vivo. Furthermore, we discuss on how phosphorylation/dephosphorylation can serve as an important mechanism of septin complex assembly and regulation.

  14. Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence

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    Jonathan P. Richardson

    2018-01-01

    Full Text Available Candida albicans is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection, C. albicans undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence. Candidalysin damages epithelial cell plasma membranes and stimulates the activating protein 1 (AP-1 transcription factor c-Fos (via p38–mitogen-activated protein kinase [MAPK], and the MAPK phosphatase MKP1 (via extracellular signal-regulated kinases 1 and 2 [ERK1/2]–MAPK, which trigger and regulate proinflammatory cytokine responses, respectively. The candidalysin toxin resides as a discrete cryptic sequence within a larger 271-amino-acid parental preproprotein, Ece1p. Here, we demonstrate that kexin-like proteinases, but not secreted aspartyl proteinases, initiate a two-step posttranslational processing of Ece1p to produce candidalysin. Kex2p-mediated proteolysis of Ece1p after Arg61 and Arg93, but not after other processing sites within Ece1p, is required to generate immature candidalysin from Ece1p, followed by Kex1p-mediated removal of a carboxyl arginine residue to generate mature candidalysin. C. albicans strains harboring mutations of Arg61 and/or Arg93 did not secrete candidalysin, were unable to induce epithelial damage and inflammatory responses in vitro, and showed attenuated virulence in vivo in a murine model of oropharyngeal candidiasis. These observations identify enzymatic processing of C. albicans Ece1p by kexin-like proteinases as crucial steps required for candidalysin production and fungal pathogenicity.

  15. Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space

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    Miao, Zhengqiang; Tan, Kaeling; Vyas, Valmik K.; Whiteway, Malcolm; Robbins, Nicole; Wong, Koon Ho; Cowen, Leah E.

    2018-01-01

    The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition. PMID:29590106

  16. Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

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    Amanda O Veri

    2018-03-01

    Full Text Available The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.

  17. Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

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    Veri, Amanda O; Miao, Zhengqiang; Shapiro, Rebecca S; Tebbji, Faiza; O'Meara, Teresa R; Kim, Sang Hu; Colazo, Juan; Tan, Kaeling; Vyas, Valmik K; Whiteway, Malcolm; Robbins, Nicole; Wong, Koon Ho; Cowen, Leah E

    2018-03-01

    The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.

  18. ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

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    Dawoon Chung

    2014-11-01

    Full Text Available The Aspergillus fumigatus sterol regulatory element binding protein (SREBP SrbA belongs to the basic Helix-Loop-Helix (bHLH family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA. How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4-sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveal new insights into SREBPs' complex role in infection site adaptation and fungal virulence.

  19. Analysis of a food-borne fungal pathogen outbreak: virulence and genome of a Mucor circinelloides isolate from yogurt.

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    Lee, Soo Chan; Billmyre, R Blake; Li, Alicia; Carson, Sandra; Sykes, Sean M; Huh, Eun Young; Mieczkowski, Piotr; Ko, Dennis C; Cuomo, Christina A; Heitman, Joseph

    2014-07-08

    Food-borne pathogens are ongoing problems, and new pathogens are emerging. The impact of fungi, however, is largely underestimated. Recently, commercial yogurts contaminated with Mucor circinelloides were sold, and >200 consumers became ill with nausea, vomiting, and diarrhea. Mucoralean fungi cause the fatal fungal infection mucormycosis, whose incidence has been continuously increasing. In this study, we isolated an M. circinelloides strain from a yogurt container, and multilocus sequence typing identified the strain as Mucor circinelloides f. circinelloides. M. circinelloides f. circinelloides is the most virulent M. circinelloides subspecies and is commonly associated with human infections, whereas M. circinelloides f. lusitanicus and M. circinelloides f. griseocyanus are less common causes of infection. Whole-genome analysis of the yogurt isolate confirmed it as being close to the M. circinelloides f. circinelloides subgroup, with a higher percentage of divergence with the M. circinelloides f. lusitanicus subgroup. In mating assays, the yogurt isolate formed sexual zygospores with the (-) M. circinelloides f. circinelloides tester strain, which is congruent with its sex locus encoding SexP, the (+) mating type sex determinant. The yogurt isolate was virulent in murine and wax moth larva host systems. In a murine gastromucormycosis model, Mucor was recovered from fecal samples of infected mice for up to 10 days, indicating that Mucor can survive transit through the GI tract. In interactions with human immune cells, M. circinelloides f. lusitanicus induced proinflammatory cytokines but M. circinelloides f. circinelloides did not, which may explain the different levels of virulence in mammalian hosts. This study demonstrates that M. circinelloides can spoil food products and cause gastrointestinal illness in consumers and may pose a particular risk to immunocompromised patients. Importance: The U.S. FDA reported that yogurt products were contaminated with M

  20. A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

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    Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

    2006-01-01

    The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

  1. The general transcriptional repressor Tup1 is required for dimorphism and virulence in a fungal plant pathogen.

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    Alberto Elías-Villalobos

    2011-09-01

    Full Text Available A critical step in the life cycle of many fungal pathogens is the transition between yeast-like growth and the formation of filamentous structures, a process known as dimorphism. This morphological shift, typically triggered by multiple environmental signals, is tightly controlled by complex genetic pathways to ensure successful pathogenic development. In animal pathogenic fungi, one of the best known regulators of dimorphism is the general transcriptional repressor, Tup1. However, the role of Tup1 in fungal dimorphism is completely unknown in plant pathogens. Here we show that Tup1 plays a key role in orchestrating the yeast to hypha transition in the maize pathogen Ustilago maydis. Deletion of the tup1 gene causes a drastic reduction in the mating and filamentation capacity of the fungus, in turn leading to a reduced virulence phenotype. In U. maydis, these processes are controlled by the a and b mating-type loci, whose expression depends on the Prf1 transcription factor. Interestingly, Δtup1 strains show a critical reduction in the expression of prf1 and that of Prf1 target genes at both loci. Moreover, we observed that Tup1 appears to regulate Prf1 activity by controlling the expression of the prf1 transcriptional activators, rop1 and hap2. Additionally, we describe a putative novel prf1 repressor, named Pac2, which seems to be an important target of Tup1 in the control of dimorphism and virulence. Furthermore, we show that Tup1 is required for full pathogenic development since tup1 deletion mutants are unable to complete the sexual cycle. Our findings establish Tup1 as a key factor coordinating dimorphism in the phytopathogen U. maydis and support a conserved role for Tup1 in the control of hypha-specific genes among animal and plant fungal pathogens.

  2. Impact of the lectin chaperone calnexin on the stress response, virulence and proteolytic secretome of the fungal pathogen Aspergillus fumigatus.

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    Margaret V Powers-Fletcher

    Full Text Available Calnexin is a membrane-bound lectin chaperone in the endoplasmic reticulum (ER that is part of a quality control system that promotes the accurate folding of glycoproteins entering the secretory pathway. We have previously shown that ER homeostasis is important for virulence of the human fungal pathogen Aspergillus fumigatus, but the contribution of calnexin has not been explored. Here, we determined the extent to which A. fumigatus relies on calnexin for growth under conditions of environmental stress and for virulence. The calnexin gene, clxA, was deleted from A. fumigatus and complemented by reconstitution with the wild type gene. Loss of clxA altered the proteolytic secretome of the fungus, but had no impact on growth rates in either minimal or complex media at 37°C. However, the ΔclxA mutant was growth impaired at temperatures above 42°C and was hypersensitive to acute ER stress caused by the reducing agent dithiothreitol. In contrast to wild type A. fumigatus, ΔclxA hyphae were unable to grow when transferred to starvation medium. In addition, depleting the medium of cations by chelation prevented ΔclxA from sustaining polarized hyphal growth, resulting in blunted hyphae with irregular morphology. Despite these abnormal stress responses, the ΔclxA mutant remained virulent in two immunologically distinct models of invasive aspergillosis. These findings demonstrate that calnexin functions are needed for growth under conditions of thermal, ER and nutrient stress, but are dispensable for surviving the stresses encountered in the host environment.

  3. The Cell Wall of the Human Fungal Pathogen Aspergillus fumigatus: Biosynthesis, Organization, Immune Response, and Virulence.

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    Latgé, Jean-Paul; Beauvais, Anne; Chamilos, Georgios

    2017-09-08

    More than 90% of the cell wall of the filamentous fungus Aspergillus fumigatus comprises polysaccharides. Biosynthesis of the cell wall polysaccharides is under the control of three types of enzymes: transmembrane synthases, which are anchored to the plasma membrane and use nucleotide sugars as substrates, and cell wall-associated transglycosidases and glycosyl hydrolases, which are responsible for remodeling the de novo synthesized polysaccharides and establishing the three-dimensional structure of the cell wall. For years, the cell wall was considered an inert exoskeleton of the fungal cell. The cell wall is now recognized as a living organelle, since the composition and cellular localization of the different constitutive cell wall components (especially of the outer layers) vary when the fungus senses changes in the external environment. The cell wall plays a major role during infection. The recognition of the fungal cell wall by the host is essential in the initiation of the immune response. The interactions between the different pattern-recognition receptors (PRRs) and cell wall pathogen-associated molecular patterns (PAMPs) orientate the host response toward either fungal death or growth, which would then lead to disease development. Understanding the molecular determinants of the interplay between the cell wall and host immunity is fundamental to combatting Aspergillus diseases.

  4. 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

  5. Δ(1-pyrroline-5-carboxylate/glutamate biogenesis is required for fungal virulence and sporulation.

    Directory of Open Access Journals (Sweden)

    Ziting Yao

    Full Text Available Proline dehydrogenase (Prodh and Δ(1-pyrroline-5-carboxylate dehydrogenase (P5Cdh are two key enzymes in the cellular biogenesis of glutamate. Recombinant Prodh and P5Cdh proteins of the chestnut blight fungus Cryphonectria parasitica were investigated and showed activity in in vitro assays. Additionally, the C. parasitica Prodh and P5Cdh genes were able to complement the Saccharomyces cerevisiae put1 and put2 null mutants, respectively, to allow these proline auxotrophic yeast mutants to grow on media with proline as the sole source of nitrogen. Deletion of the Prodh gene in C. parasitica resulted in hypovirulence and a lower level of sporulation, whereas deletion of P5Cdh resulted in hypovirulence though no effect on sporulation; both Δprodh and Δp5cdh mutants were unable to grow on minimal medium with proline as the sole nitrogen source. In a wild-type strain, the intracellular level of proline and the activity of Prodh and P5Cdh increased after supplementation of exogenous proline, though the intracellular Δ(1-pyrroline-5-carboxylate (P5C content remained unchanged. Prodh and P5Cdh were both transcriptionally down-regulated in cells infected with hypovirus. The disruption of other genes with products involved in the conversion of arginine to ornithine, ornithine and glutamate to P5C, and P5C to proline in the cytosol did not appear to affect virulence; however, asexual sporulation was reduced in the Δpro1 and Δpro2 mutants. Taken together, our results showed that Prodh, P5Cdh and related mitochondrial functions are essential for virulence and that proline/glutamate pathway components may represent down-stream targets of hypovirus regulation in C. parasitica.

  6. Cloning of Beauveria bassiana chitinase gene Bbchit1 and its application to improve fungal strain virulence.

    Science.gov (United States)

    Fang, Weiguo; Leng, Bo; Xiao, Yuehua; Jin, Kai; Ma, Jincheng; Fan, Yanhua; Feng, Jing; Yang, Xingyong; Zhang, Yongjun; Pei, Yan

    2005-01-01

    Entomopathogenic fungi can produce a series of chitinases, some of which act synergistically with proteases to degrade insect cuticle. However, chitinase involvement in insect fungus pathogenesis has not been fully characterized. In this paper, an endochitinase, Bbchit1, was purified to homogeneity from liquid cultures of Beauveria bassiana grown in a medium containing colloidal chitin. Bbchit1 had a molecular mass of about 33 kDa and pI of 5.4. Based on the N-terminal amino acid sequence, the chitinase gene, Bbchit1, and its upstream regulatory sequence were cloned. Bbchit1 was intronless, and there was a single copy in B. bassiana. Its regulatory sequence contained putative CreA/Crel carbon catabolic repressor binding domains, which was consistent with glucose suppression of Bbchit1. At the amino acid level, Bbchit1 showed significant similarity to a Streptomyces avermitilis putative endochitinase, a Streptomyces coelicolor putative chitinase, and Trichoderma harzianum endochitinase Chit36Y. However, Bbchit1 had very low levels of identity to other chitinase genes previously isolated from entomopathogenic fungi, indicating that Bbchit1 was a novel chitinase gene from an insect-pathogenic fungus. A gpd-Bbchit1 construct, in which Bbchit1 was driven by the Aspergiullus nidulans constitutive promoter, was transformed into the genome of B. bassiana, and three transformants that overproduced Bbchit1 were obtained. Insect bioassays revealed that overproduction of Bbchit1 enhanced the virulence of B. bassiana for aphids, as indicated by significantly lower 50% lethal concentrations and 50% lethal times of the transformants compared to the values for the wild-type strain.

  7. Secretome Analysis Identifies Potential Pathogenicity/Virulence Factors of Tilletia indica, a Quarantined Fungal Pathogen Inciting Karnal Bunt Disease in Wheat.

    Science.gov (United States)

    Pandey, Vishakha; Singh, Manoj; Pandey, Dinesh; Marla, Soma; Kumar, Anil

    2018-04-01

    Tilletia indica is a smut fungus that incites Karnal bunt in wheat. It has been considered as quarantine pest in more than 70 countries. Despite its quarantine significance, there is meager knowledge regarding the molecular mechanisms of disease pathogenesis. Moreover, various disease management strategies have proven futile. Development of effective disease management strategy requires identification of pathogenicity/virulence factors. With this aim, the present study was conducted to compare the secretomes of T. indica isolates, that is, highly (TiK) and low (TiP) virulent isolates. About 120 and 95 protein spots were detected reproducibly in TiK and TiP secretome gel images. Nineteen protein spots, which were consistently observed as upregulated/differential in the secretome of TiK isolate, were selected for their identification by MALDI-TOF/TOF. Identified proteins exhibited homology with fungal proteins playing important role in fungal adhesion, penetration, invasion, protection against host-derived reactive oxygen species, production of virulence factors, cellular signaling, and degradation of host cell wall proteins and antifungal proteins. These results were complemented with T. indica genome sequence leading to identification of candidate pathogenicity/virulence factors homologs that were further subjected to sequence- and structure-based functional annotation. Thus, present study reports the first comparative secretome analysis of T. indica for identification of pathogenicity/virulence factors. This would provide insights into pathogenic mechanisms of T. indica and aid in devising effective disease management strategies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. DNA methyltransferases contribute to the fungal development, stress tolerance and virulence of the entomopathogenic fungus Metarhizium robertsii.

    Science.gov (United States)

    Wang, Yulong; Wang, Tiantian; Qiao, Lintao; Zhu, Jianyu; Fan, Jinrui; Zhang, Tingting; Wang, Zhang-Xun; Li, Wanzhen; Chen, Anhui; Huang, Bo

    2017-05-01

    DNA methylation is an important epigenetic mark in mammals, plants, and fungi and depends on multiple genetic pathways involving de novo and maintenance DNA methyltransferases (DNMTases). Metarhizium robertsii, a model system for investigating insect-fungus interactions, has been used as an environmentally friendly alternative to chemical insecticides. However, little is known concerning the molecular basis for DNA methylation. Here, we report on the roles of two DNMTases (MrRID and MrDIM-2) by characterizing ΔMrRID, ΔMrDIM-2, and ΔRID/ΔDIM-2 mutants. The results showed that approximately 71, 10, and 8% of m C sites remained in the ΔMrRID, ΔMrDIM-2, and ΔRID/ΔDIM-2 strains, respectively, compared with the wild-type (WT) strain. Further analysis showed that MrRID regulates the specificity of DNA methylation and MrDIM-2 is responsible for most DNA methylation, implying an interaction or cooperation between MrRID and MrDIM-2 for DNA methylation. Moreover, the ΔMrDIM-2 and ΔRID/ΔDIM-2 strains showed more defects in radial growth and conidial production compared to the WT. Under ultraviolet (UV) irradiation or heat stress, an obvious reduction in spore viability was observed for all the mutant strains compared to the WT. The spore median lethal times (LT 50 s) for the ΔMrDIM-2 and ΔRID/ΔDIM-2 strains in the greater wax moth, Galleria mellonella, were decreased by 47.7 and 65.9%, respectively, which showed that MrDIM-2 is required for full fungal virulence. Our data advances the understanding of the function of DNMTase in entomopathogenic fungi, which should contribute to future epigenetic investigations in fungi.

  9. The Crucial Role of the Pls1 Tetraspanin during Ascospore Germination in Podospora anserina Provides an Example of the Convergent Evolution of Morphogenetic Processes in Fungal Plant Pathogens and Saprobes▿ †

    Science.gov (United States)

    Lambou, Karine; Malagnac, Fabienne; Barbisan, Crystel; Tharreau, Didier; Lebrun, Marc-Henri; Silar, Philippe

    2008-01-01

    Pls1 tetraspanins were shown for some pathogenic fungi to be essential for appressorium-mediated penetration into their host plants. We show here that Podospora anserina, a saprobic fungus lacking appressorium, contains PaPls1, a gene orthologous to known PLS1 genes. Inactivation of PaPls1 demonstrates that this gene is specifically required for the germination of ascospores in P. anserina. These ascospores are heavily melanized cells that germinate under inducing conditions through a specific pore. On the contrary, MgPLS1, which fully complements a ΔPaPls1 ascospore germination defect, has no role in the germination of Magnaporthe grisea nonmelanized ascospores but is required for the formation of the penetration peg at the pore of its melanized appressorium. P. anserina mutants with mutation of PaNox2, which encodes the NADPH oxidase of the NOX2 family, display the same ascospore-specific germination defect as the ΔPaPls1 mutant. Both mutant phenotypes are suppressed by the inhibition of melanin biosynthesis, suggesting that they are involved in the same cellular process required for the germination of P. anserina melanized ascospores. The analysis of the distribution of PLS1 and NOX2 genes in fungal genomes shows that they are either both present or both absent. These results indicate that the germination of P. anserina ascospores and the formation of the M. grisea appressorium penetration peg use the same molecular machinery that includes Pls1 and Nox2. This machinery is specifically required for the emergence of polarized hyphae from reinforced structures such as appressoria and ascospores. Its recurrent recruitment during fungal evolution may account for some of the morphogenetic convergence observed in fungi. PMID:18757568

  10. The crucial role of the Pls1 tetraspanin during ascospore germination in Podospora anserina provides an example of the convergent evolution of morphogenetic processes in fungal plant pathogens and saprobes.

    Science.gov (United States)

    Lambou, Karine; Malagnac, Fabienne; Barbisan, Crystel; Tharreau, Didier; Lebrun, Marc-Henri; Silar, Philippe

    2008-10-01

    Pls1 tetraspanins were shown for some pathogenic fungi to be essential for appressorium-mediated penetration into their host plants. We show here that Podospora anserina, a saprobic fungus lacking appressorium, contains PaPls1, a gene orthologous to known PLS1 genes. Inactivation of PaPls1 demonstrates that this gene is specifically required for the germination of ascospores in P. anserina. These ascospores are heavily melanized cells that germinate under inducing conditions through a specific pore. On the contrary, MgPLS1, which fully complements a DeltaPaPls1 ascospore germination defect, has no role in the germination of Magnaporthe grisea nonmelanized ascospores but is required for the formation of the penetration peg at the pore of its melanized appressorium. P. anserina mutants with mutation of PaNox2, which encodes the NADPH oxidase of the NOX2 family, display the same ascospore-specific germination defect as the DeltaPaPls1 mutant. Both mutant phenotypes are suppressed by the inhibition of melanin biosynthesis, suggesting that they are involved in the same cellular process required for the germination of P. anserina melanized ascospores. The analysis of the distribution of PLS1 and NOX2 genes in fungal genomes shows that they are either both present or both absent. These results indicate that the germination of P. anserina ascospores and the formation of the M. grisea appressorium penetration peg use the same molecular machinery that includes Pls1 and Nox2. This machinery is specifically required for the emergence of polarized hyphae from reinforced structures such as appressoria and ascospores. Its recurrent recruitment during fungal evolution may account for some of the morphogenetic convergence observed in fungi.

  11. The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Li, Xichuan; Du, Wei; Zhao, Jingwen; Zhang, Lilin; Zhu, Zhiyan; Jiang, Linghuo

    2010-06-01

    Rck2p is the Hog1p-MAP kinase-activated protein kinase required for the attenuation of protein synthesis in response to an osmotic challenge in Saccharomyces cerevisiae. Rck2p also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. In this study, we demonstrate that the deletion of CaRCK2 renders C. albicans cells sensitive to, and CaRck2p translocates from the cytosol to the nucleus in response to, cell wall stresses caused by Congo red, Calcoflor White, elevated heat and zymolyase. However, the kinase activity of CaRck2p is not required for the cellular response to these cell wall stresses. Furthermore, transcripts of cell wall protein-encoding genes CaBGL2, CaHWP1 and CaXOG1 are reduced in C. albicans cells lacking CaRCK2. The deletion of CaRCK2 also reduces the in vitro filamentation of C. albicans and its virulence in a mouse model of systemic candidasis. The kinase activity of CaRck2p is required for the virulence, but not for the in vitro filamentation, in C. albicans. Therefore, Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen C. albicans.

  12. TmpL, a transmembrane protein required for intracellular redox homeostasis and virulence in a plant and an animal fungal pathogen.

    Directory of Open Access Journals (Sweden)

    Kwang-Hyung Kim

    2009-11-01

    have discovered a novel protein involved in the virulence of both plant and animal fungal pathogens. Our results strongly suggest that dysregulation of oxidative stress homeostasis in the absence of TmpL is the underpinning cause of the developmental and virulence defects observed in these studies.

  13. Fusarium oxysporum f. sp. dianthi virus 1 accumulation is correlated with changes in virulence and other phenotypic traits of its fungal host.

    Science.gov (United States)

    Lemus-Minor, Carlos German; Cañizares-Nolasco, Carmen; García-Pedrajas, Maria D D; Pérez-Artés, Encarnación

    2018-03-08

    Fusarium oxysporum f. sp. dianthi virus 1 (FodV1) was detected in isolate Fod 116 (Fod 116V + ) of Fusarium oxysporum f. sp. dianthi (Fod), reaching such a high accumulation level that it was clearly visible after agarose gel electrophoresis of total DNA extracts. FodV1 consists of four double-stranded RNA segments, that correspond to a new mycovirus in the Chrysoviridae family. We obtained an isolate of Fod 116 (Fod 116V - ) with only a residual level of FodV1 RNA accumulation by single-conidia selection. Compared to the Fod 116V - , isolate Fod 116V + showed significant phenotypic alterations in vegetative growth and virulence. The presence of a high titer of mycovirus FodV1 thus associated with a modified morphology and a reduced growth of the colonies on solid medium, and with a diminished conidiation in liquid medium. Inoculation of four susceptible carnation cultivars with either Fod 116V - or Fod 116V + showed that the presence of a high titer of FodV1 was also correlated with a significantly reduced virulence of its fungal host. All the results suggest that FodV1 could be associated with hypovirulence, identifying it as a potential biocontrol agent against Fusarium wilt of carnation. This is the first report of a mycovirus potentially associated to the induction of hypovirulence in the species Fusarium oxysporum.

  14. New insights into the in vitro development and virulence of Culicinomyces spp. as fungal pathogens of Aedes aegypti

    Science.gov (United States)

    Culicinomyces spp. (Hypocreales: Cordycipitaceae) are facultative fungal pathogens affecting the larval stages from a range of mosquito species and are especially notable in their ability to infect hosts through the digestive tract after conidial ingestion. While Culicinomyces spp. were studied main...

  15. A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Cheryl D Chun

    2007-02-01

    Full Text Available Fungal pathogens of humans require molecular oxygen for several essential biochemical reactions, yet virtually nothing is known about how they adapt to the relatively hypoxic environment of infected tissues. We isolated mutants defective in growth under hypoxic conditions, but normal for growth in normoxic conditions, in Cryptococcus neoformans, the most common cause of fungal meningitis. Two regulatory pathways were identified: one homologous to the mammalian sterol-response element binding protein (SREBP cholesterol biosynthesis regulatory pathway, and the other a two-component-like pathway involving a fungal-specific hybrid histidine kinase family member, Tco1. We show that cleavage of the SREBP precursor homolog Sre1-which is predicted to release its DNA-binding domain from the membrane-occurs in response to hypoxia, and that Sre1 is required for hypoxic induction of genes encoding for oxygen-dependent enzymes involved in ergosterol synthesis. Importantly, mutants in either the SREBP pathway or the Tco1 pathway display defects in their ability to proliferate in host tissues and to cause disease in infected mice, linking for the first time to our knowledge hypoxic adaptation and pathogenesis by a eukaryotic aerobe. SREBP pathway mutants were found to be a hundred times more sensitive than wild-type to fluconazole, a widely used antifungal agent that inhibits ergosterol synthesis, suggesting that inhibitors of SREBP processing could substantially enhance the potency of current therapies.

  16. Introduction to morphogenetic computing

    CERN Document Server

    Resconi, Germano; Xu, Guanglin

    2017-01-01

    This book offers a concise introduction to morphogenetic computing, showing that its use makes global and local relations, defects in crystal non-Euclidean geometry databases with source and sink, genetic algorithms, and neural networks more stable and efficient. It also presents applications to database, language, nanotechnology with defects, biological genetic structure, electrical circuit, and big data structure. In Turing machines, input and output states form a system – when the system is in one state, the input is transformed into output. This computation is always deterministic and without any possible contradiction or defects. In natural computation there are defects and contradictions that have to be solved to give a coherent and effective computation. The new computation generates the morphology of the system that assumes different forms in time. Genetic process is the prototype of the morphogenetic computing. At the Boolean logic truth value, we substitute a set of truth (active sets) values with...

  17. The classic: Bone morphogenetic protein.

    Science.gov (United States)

    Urist, Marshall R; Strates, Basil S

    2009-12-01

    This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is copyright 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res. 1971;50:1392-1406.

  18. An aldo-keto reductase, Bbakr1, is involved in stress response and detoxification of heavy metal chromium but not required for virulence in the insect fungal pathogen, Beauveria bassiana.

    Science.gov (United States)

    Wang, Huifang; He, Zhangjiang; Luo, Linli; Zhao, Xin; Lu, Zhuoyue; Luo, Tingying; Li, Min; Zhang, Yongjun

    2018-02-01

    The aldo-keto reductases (AKRs) belong to the NADP-dependent oxidoreductase superfamily, which play important roles in various physiological functions in prokaryotic and eukaryotic organisms. However, many AKR superfamily members remain uncharacterized. Here, a downstream target gene of the HOG1 MAPK pathways coding for an aldo-keto reductase, named Bbakr1, was characterized in the insect fungal pathogen, Beauveria bassiana. Bbakr1 expression increased in response to osmotic and salt stressors, and oxidative and heavy metal (chromium) stress. Deletion of Bbakr1 caused a reduction in conidiation, as well as delayed conidial germination. ΔBbakr1 displayed increased sensitivity to osmotic/high-salt stress with decreased compatible solute accumulation. In addition, the mutant was more sensitive to high concentrations of the heavy metal, chromium, and to oxidative stress than the wild type cells, with impaired ability to detoxify active aldehyde that might accumulate due to lipid peroxidation. However, over-expressing Bbakr1 in either the wild type strain or a ΔBbhog1 background did not cause any obvious changes in phenotypes as compared to their controls. Little effect on virulence was seen for either the ΔBbakr1 or overexpression strains in insect bioassays via cuticle infection or intrahemocoel injection assays, suggesting that Bbakr1 is not required for virulence. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  20. Morphogenetic Litter Types of Bog Spruce Forests

    Directory of Open Access Journals (Sweden)

    T. T. Efremova

    2015-02-01

    Full Text Available For the first time the representation of moss litter morphogenetic structure of valley-riverside and streamside spruce forests was determined for the wetland intermountain area of Kuznetsk Alatau. In general, the litter of (green moss-hypnum spruce forest can be characterized as medium thickness (9–17 cm with high storage of organic matter (77–99 t/ha, which differs in neutral environmental conditions pH 6.8–7.0 and high percentage of ash 11–28 %. Formation litter types were identified, which depend on the content of mineral inclusions in organogenic substrate and the degree of its drainage. The differentiation of litter subhorizons was performed, visual diagnostic indicators of fermentative layers were characterized, and additional (indexes to indicate their specificity were developed. Peat- and peaty-fermentative, humified-fermentative and (black mold humus-fermentative layers were selected. Peat- and peaty-fermentative layers are characterized by content of platy peat macroaggregates of coarse vegetable composition, the presence of abundant fungal mycelium and soil animals are the primary decomposers – myriopoda, gastropoda mollusks. Humified-fermentative layers are identified by including the newly formed amorphous humus-like substances, nutty-granular structural parts of humus nature and soil animals’ humificators – enchytraeids and earthworms. (Black mold humus-fermentative layers are diagnosed by indicators with similar humified-fermentative, but differ from them in clay-humus composition of nutty-granular blue-grey parts. The nomenclature and classification of moss litter were developed on the basis of their diagnostic characteristics of fermentative layers – peat, peaty, reduced peaty, (black mold humus-peaty, reduced (black mold humus-peaty. Using the method of discriminant analysis, we revealed that the physical-chemical properties, mainly percentage of ash and decomposition degree of plant substrate, objectively

  1. Interplay between calcineurin and the Slt2 MAP-kinase in mediating cell wall integrity, conidiation and virulence in the insect fungal pathogen Beauveria bassiana.

    Science.gov (United States)

    Huang, Shuaishuai; He, Zhangjiang; Zhang, Shiwei; Keyhani, Nemat O; Song, Yulin; Yang, Zhi; Jiang, Yahui; Zhang, Wenli; Pei, Yan; Zhang, Yongjun

    2015-10-01

    The entomopathogenic fungus, Beauveria bassiana, is of environmental and economic importance as an insect pathogen, currently used for the biological control of a number of pests. Cell wall integrity and conidiation are critical parameters for the ability of the fungus to infect insects and for production of the infectious propagules. The contribution of calcineurin and the Slt2 MAP kinase to cell wall integrity and development in B. bassiana was investigated. Gene knockouts of either the calcineurin CNA1 subunit or the Slt2 MAP kinase resulted in decreased tolerance to calcofluor white and high temperature. In contrast, the Δcna1 strain was more tolerant to Congo red but more sensitive to osmotic stress (NaCl, sorbitol) than the wild type, whereas the Δslt2 strain had the opposite phenotype. Changes in cell wall structure and composition were seen in the Δslt2 and Δcna1 strains during growth under cell wall stress as compared to the wild type. Both Δslt2 and Δcna1 strains showed significant alterations in growth, conidiation, and viability. Elevation of intracellular ROS levels, and decreased conidial hydrophobicity and adhesion to hydrophobic surfaces, were also seen for both mutants, as well as decreased virulence. Under cell wall stress conditions, inactivation of Slt2 significantly repressed CN-mediated phosphatase activity suggesting some level of cross talk between the two pathways. Comparative transcriptome profiling of the Δslt2 and Δcna1 strains revealed alterations in the expression of distinct gene sets, with overlap in transcripts involved in cell wall integrity, stress response, conidiation and virulence. These data illustrate convergent and divergent phenotypes and targets of the calcineurin and Slt2 pathways in B. bassiana. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Fungal Meningitis

    Science.gov (United States)

    ... Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Fungal Meningitis Language: English Spanish Recommend on Facebook Tweet Share ... the brain or spinal cord. Investigation of Fungal Meningitis, 2012 In September 2012, the Centers for Disease ...

  3. Bone morphogenetic protein signalling in colorectal cancer

    NARCIS (Netherlands)

    Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

    2008-01-01

    Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The

  4. Fungal Endocarditis.

    Science.gov (United States)

    Yuan, Shi-Min

    2016-01-01

    Fungal endocarditis is a rare and fatal condition. The Candida and Aspergillus species are the two most common etiologic fungi found responsible for fungal endocarditis. Fever and changing heart murmur are the most common clinical manifestations. Some patients may have a fever of unknown origin as the onset symptom. The diagnosis of fungal endocarditis is challenging, and diagnosis of prosthetic valve fungal endocarditis is extremely difficult. The optimum antifungal therapy still remains debatable. Treating Candida endocarditis can be difficult because the Candida species can form biofilms on native and prosthetic heart valves. Combined treatment appears superior to monotherapy. Combination of antifungal therapy and surgical debridement might bring about better prognosis.

  5. Are secondary metabolites dispensable for virulence?

    Science.gov (United States)

    The production of toxins by conidial fungal pathogens and their association with virulence has been assumed to occur in vivo and is widely accepted as dogma, but this association has yet to be definitively proven by either genetic or chemical means. Several studies from our labs have used targeted g...

  6. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi

    1998-01-01

    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  7. Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis.

    Science.gov (United States)

    Teixeira, Marcus M; de Almeida, Luiz G P; Kubitschek-Barreira, Paula; Alves, Fernanda L; Kioshima, Erika S; Abadio, Ana K R; Fernandes, Larissa; Derengowski, Lorena S; Ferreira, Karen S; Souza, Rangel C; Ruiz, Jeronimo C; de Andrade, Nathalia C; Paes, Hugo C; Nicola, André M; Albuquerque, Patrícia; Gerber, Alexandra L; Martins, Vicente P; Peconick, Luisa D F; Neto, Alan Viggiano; Chaucanez, Claudia B; Silva, Patrícia A; Cunha, Oberdan L; de Oliveira, Fabiana F M; dos Santos, Tayná C; Barros, Amanda L N; Soares, Marco A; de Oliveira, Luciana M; Marini, Marjorie M; Villalobos-Duno, Héctor; Cunha, Marcel M L; de Hoog, Sybren; da Silveira, José F; Henrissat, Bernard; Niño-Vega, Gustavo A; Cisalpino, Patrícia S; Mora-Montes, Héctor M; Almeida, Sandro R; Stajich, Jason E; Lopes-Bezerra, Leila M; Vasconcelos, Ana T R; Felipe, Maria S S

    2014-10-29

    Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis.

  8. Morphogenetic Engineering Toward Programmable Complex Systems

    CERN Document Server

    Sayama, Hiroki; Michel, Olivier

    2012-01-01

    Generally, spontaneous pattern formation phenomena are random and repetitive, whereas elaborate devices are the deterministic product of human design. Yet, biological organisms and collective insect constructions are exceptional examples of complex systems that are both self-organized and architectural.   This book is the first initiative of its kind toward establishing a new field of research, Morphogenetic Engineering, to explore the modeling and implementation of “self-architecturing” systems. Particular emphasis is placed on the programmability and computational abilities of self-organization, properties that are often underappreciated in complex systems science—while, conversely, the benefits of self-organization are often underappreciated in engineering methodologies.   Altogether, the aim of this work is to provide a framework for and examples of a larger class of “self-architecturing” systems, while addressing fundamental questions such as   > How do biological organisms carry out morphog...

  9. Evolution and genome architecture in fungal plant pathogens.

    Science.gov (United States)

    Möller, Mareike; Stukenbrock, Eva H

    2017-12-01

    The fungal kingdom comprises some of the most devastating plant pathogens. Sequencing the genomes of fungal pathogens has shown a remarkable variability in genome size and architecture. Population genomic data enable us to understand the mechanisms and the history of changes in genome size and adaptive evolution in plant pathogens. Although transposable elements predominantly have negative effects on their host, fungal pathogens provide prominent examples of advantageous associations between rapidly evolving transposable elements and virulence genes that cause variation in virulence phenotypes. By providing homogeneous environments at large regional scales, managed ecosystems, such as modern agriculture, can be conducive for the rapid evolution and dispersal of pathogens. In this Review, we summarize key examples from fungal plant pathogen genomics and discuss evolutionary processes in pathogenic fungi in the context of molecular evolution, population genomics and agriculture.

  10. The link between morphotype transition and virulence in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Linqi Wang

    Full Text Available Cryptococcus neoformans is a ubiquitous human fungal pathogen. This pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. Morphotype transition is typically observed during mating, which is governed by pheromone signaling. Paradoxically, components specific to the pheromone signaling pathways play no or minimal direct roles in virulence. Thus, the link between morphotype transition and virulence and the underlying molecular mechanism remain elusive. Here, we demonstrate that filamentation can occur independent of pheromone signaling and mating, and both mating-dependent and mating-independent morphotype transition require the transcription factor Znf2. High expression of Znf2 is necessary and sufficient to initiate and maintain sex-independent filamentous growth under host-relevant conditions in vitro and during infection. Importantly, ZNF2 overexpression abolishes fungal virulence in murine models of cryptococcosis. Thus, Znf2 bridges the sex-independent morphotype transition and fungal pathogenicity. The impacts of Znf2 on morphological switch and pathogenicity are at least partly mediated through its effects on cell adhesion property. Cfl1, a Znf2 downstream factor, regulates morphogenesis, cell adhesion, biofilm formation, and virulence. Cfl1 is the first adhesin discovered in the phylum Basidiomycota of the Kingdom Fungi. Together with previous findings in other eukaryotic pathogens, our findings support a convergent evolution of plasticity in morphology and its impact on cell adhesion as a critical adaptive trait for pathogenesis.

  11. Nuclear variants of bone morphogenetic proteins

    Directory of Open Access Journals (Sweden)

    Meinhart Christopher A

    2010-03-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts. Results In all three proteins, a bipartite nuclear localization signal (NLS was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5 containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle. Conclusions The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.

  12. Use of Metarhizium anisopliae Chitinase Genes for Genotyping and Virulence Characterization

    Directory of Open Access Journals (Sweden)

    Saliou Niassy

    2013-01-01

    Full Text Available Virulence is the primary factor used for selection of entomopathogenic fungi (EPF for development as biopesticides. To understand the genetic mechanisms underlying differences in virulence of fungal isolates on various arthropod pests, we compared the chitinase genes, chi2 and chi4, of 8 isolates of Metarhizium anisopliae. The clustering of the isolates showed various groups depending on their virulence. However, the analysis of their chitinase DNA sequences chi2 and chi4 did not reveal major divergences. Although their protein translates have been implicated in fungal virulence, the predicted protein structure of chi2 was identical for all isolates. Despite the critical role of chitin digestion in fungal infection, we conclude that chi2 and chi4 genes cannot serve as molecular markers to characterize observed variations in virulence among M. anisopliae isolates as previously suggested. Nevertheless, processes controlling the efficient upregulation of chitinase expression might be responsible for different virulence characteristics. Further studies using comparative “in vitro” chitin digestion techniques would be more appropriate to compare the quality and the quantity of chitinase production between fungal isolates.

  13. [Iron and invasive fungal infection].

    Science.gov (United States)

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  14. Enzymes and fungal virulence | Tonukari | Journal of Applied ...

    African Journals Online (AJOL)

    This paper presents a comprehensive literature review of cell wall degrading enzymes (CWDEs). Plant pathogenic fungi secrete extracellular enzymes that are capable of degrading the cell walls of their host plants. These CWDEs may be necessary for penetration of the cell wall barrier, as well as for generation of simple ...

  15. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Science.gov (United States)

    Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

    2007-07-27

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  16. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Directory of Open Access Journals (Sweden)

    Eleftherios Mylonakis

    2007-07-01

    Full Text Available Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  17. Invasive mold infections : virulence and pathogenesis of mucorales

    OpenAIRE

    Morace, G.; Borghi, E.

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the...

  18. 50-plus years of fungal viruses

    Energy Technology Data Exchange (ETDEWEB)

    Ghabrial, Said A., E-mail: saghab00@email.uky.edu [Plant Pathology Department, University of Kentucky, Lexington, KY (United States); Castón, José R. [Department of Structure of Macromolecules, Centro Nacional Biotecnologıa/CSIC, Campus de Cantoblanco, Madrid (Spain); Jiang, Daohong [State Key Lab of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei Province (China); Nibert, Max L. [Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA (United States); Suzuki, Nobuhiro [Institute of Plant Science and Resources, Okayama University, Kurashiki, Okayama (Japan)

    2015-05-15

    Mycoviruses are widespread in all major taxa of fungi. They are transmitted intracellularly during cell division, sporogenesis, and/or cell-to-cell fusion (hyphal anastomosis), and thus their life cycles generally lack an extracellular phase. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups, although recent advances have established expanded experimental host ranges for some mycoviruses. Most known mycoviruses have dsRNA genomes packaged in isometric particles, but an increasing number of positive- or negative-strand ssRNA and ssDNA viruses have been isolated and characterized. Although many mycoviruses do not have marked effects on their hosts, those that reduce the virulence of their phytopathogenic fungal hosts are of considerable interest for development of novel biocontrol strategies. Mycoviruses that infect endophytic fungi and those that encode killer toxins are also of special interest. Structural analyses of mycoviruses have promoted better understanding of virus assembly, function, and evolution. - Highlights: • Historical perspective of fungal virus research. • Description, classification and diversity of fungal virus families. • Structural features of fungal virus particles. • Hypovirulence and exploitation of mycoviruses in biological control of plant pathogenic fungi.

  19. The virulence of human pathogenic fungi: notes from the South of France.

    Science.gov (United States)

    Reedy, Jennifer L; Bastidas, Robert J; Heitman, Joseph

    2007-08-16

    The Second FEBS Advanced Lecture Course on Human Fungal Pathogens: Molecular Mechanisms of Host-Pathogen Interactions and Virulence, organized by Christophe d'Enfert (Institut Pasteur, France), Anita Sil (UCSF, USA), and Steffen Rupp (Fraunhofer, IGB, Germany), occurred May 2007 in La Colle sur Loup, France. Here we review the advances presented and the current state of knowledge in key areas of fungal pathogenesis.

  20. Fungal melanin: what do we know about structure?

    Directory of Open Access Journals (Sweden)

    Joshua D Nosanchuk

    2015-12-01

    Full Text Available The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.

  1. Models of Caenorhabditis elegans infection by bacterial and fungal pathogens.

    Science.gov (United States)

    Powell, Jennifer R; Ausubel, Frederick M

    2008-01-01

    The nematode Caenorhabditis elegans is a simple model host for studying the relationship between the animal innate immune system and a variety of bacterial and fungal pathogens. Extensive genetic and molecular tools are available in C. elegans, facilitating an in-depth analysis of host defense factors and pathogen virulence factors. Many of these factors are conserved in insects and mammals, indicating the relevance of the nematode model to the vertebrate innate immune response. Here, we describe pathogen assays for a selection of the most commonly studied bacterial and fungal pathogens using the C. elegans model system.

  2. Functional analysis of the conserved transcriptional regulator CfWor1 in Cladosporium fulvum reveals diverse roles in the virulence of plant pathogenic fungi

    NARCIS (Netherlands)

    Ökmen, B.; Collemare, J.; Griffiths, S.A.; Burgt, van der A.; Cox, R.; Wit, de P.J.G.M.

    2014-01-01

    Fungal Wor1-like proteins are conserved transcriptional regulators that are reported to regulate the virulence of several plant pathogenic fungi by affecting the expression of virulence genes. Here, we report the functional analysis of CfWor1, the homologue of Wor1 in Cladosporium fulvum. ¿cfwor1

  3. Freshwater Fungal Infections

    Directory of Open Access Journals (Sweden)

    Dennis J. Baumgardner

    2017-01-01

    Full Text Available Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails to resolve with appropriate antibacterial therapy.

  4. Fungal Melanin: What do We Know About Structure?

    OpenAIRE

    Nosanchuk, Joshua D.; Stark, Ruth E.; Casadevall, Arturo

    2015-01-01

    The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositio...

  5. Candida albicans isolated from urine: Phenotypic and molecular identification, virulence factors and antifungal susceptibility

    Directory of Open Access Journals (Sweden)

    Laura Wiebusch

    2017-07-01

    Conclusions: C. albicans isolates from urine have a high capacity for virulence and can be associated with infectious processes. Furthermore, the high percentage of isolates resistant to itraconazole is important because this antifungal agent is commonly used to treat fungal infections in the hospital environment.

  6. Mixed infections reveal virulence differences between host-specific bee pathogens.

    Science.gov (United States)

    Klinger, Ellen G; Vojvodic, Svjetlana; DeGrandi-Hoffman, Gloria; Welker, Dennis L; James, Rosalind R

    2015-07-01

    Dynamics of host-pathogen interactions are complex, often influencing the ecology, evolution and behavior of both the host and pathogen. In the natural world, infections with multiple pathogens are common, yet due to their complexity, interactions can be difficult to predict and study. Mathematical models help facilitate our understanding of these evolutionary processes, but empirical data are needed to test model assumptions and predictions. We used two common theoretical models regarding mixed infections (superinfection and co-infection) to determine which model assumptions best described a group of fungal pathogens closely associated with bees. We tested three fungal species, Ascosphaera apis, Ascosphaera aggregata and Ascosphaera larvis, in two bee hosts (Apis mellifera and Megachile rotundata). Bee survival was not significantly different in mixed infections vs. solo infections with the most virulent pathogen for either host, but fungal growth within the host was significantly altered by mixed infections. In the host A. mellifera, only the most virulent pathogen was present in the host post-infection (indicating superinfective properties). In M. rotundata, the most virulent pathogen co-existed with the lesser-virulent one (indicating co-infective properties). We demonstrated that the competitive outcomes of mixed infections were host-specific, indicating strong host specificity among these fungal bee pathogens. Published by Elsevier Inc.

  7. Transient virulence of emerging pathogens.

    Science.gov (United States)

    Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

    2010-05-06

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

  8. [Virulence of Sporothrix globosa in murine models].

    Science.gov (United States)

    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  10. cipC is important for Aspergillus fumigatus virulence.

    Science.gov (United States)

    Canela, Heliara Maria Spina; Takami, Luciano Akira; da Silva Ferreira, Márcia Eliana

    2017-02-01

    Aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. We previously observed that the transcription of a cipC-like gene was increased when A. fumigatus encountered an increased CO 2 concentration, as occurs during the infection process. CipC is a protein of unknown function that might be associated with fungal pathogenicity. In this study, the cipC gene was disrupted in A. fumigatus to evaluate its importance for fungal pathogenicity. The gene was replaced, and the germination, growth phenotype, stress responses, and virulence of the resultant mutant were assessed. Although cipC was not essential, its deletion attenuated A. fumigatus virulence in a low-dose murine infection model, suggesting the involvement of the cipC gene in the virulence of this fungus. This study is the first to disrupt the cipC gene in A. fumigatus. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  11. Fungal Skin Infections

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... touching the infected area. Diagnosis Skin scrapings or cultures Doctors may suspect a fungal infection when they ...

  12. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  13. Fungal symbiosis unearthed

    Science.gov (United States)

    Daniel Cullen

    2008-01-01

    Associations between plant roots and fungi are a feature of many terrestrial ecosystems. The genome sequence of a prominent fungal partner opens new avenues for studying such mycorrhizal interactions....

  14. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

    Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

    1990-01-01

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

  15. A Morphogenetic Design Approach with Embedded Structural Analysis

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Kirkegaard, Poul Henning; Holst, Malene Kirstine

    2010-01-01

    The present paper explores a morphogenetic design approach with embedded structural analysis for architectural design. A material system based on a combined space truss and membrane system has been derived as a growth system with inspiration from natural growth of plants. The structural system...... is capable of adding new elements based on a structural analysis of the existing components and their internal stress levels. A GA decision-making procedure that control the generation of the growth cycles is introduced. This evaluation and generation loop is capable of successfully making decisions based...... on several, and often conflicting, inputs formulated from architectural requirements. An experiment with a tri-pyramid component has been considered, but many other space truss systems could be explored in the same manner and result in highly performative outcomes. not only with respect to the structural...

  16. Biomimetic design processes in architecture: morphogenetic and evolutionary computational design

    International Nuclear Information System (INIS)

    Menges, Achim

    2012-01-01

    Design computation has profound impact on architectural design methods. This paper explains how computational design enables the development of biomimetic design processes specific to architecture, and how they need to be significantly different from established biomimetic processes in engineering disciplines. The paper first explains the fundamental difference between computer-aided and computational design in architecture, as the understanding of this distinction is of critical importance for the research presented. Thereafter, the conceptual relation and possible transfer of principles from natural morphogenesis to design computation are introduced and the related developments of generative, feature-based, constraint-based, process-based and feedback-based computational design methods are presented. This morphogenetic design research is then related to exploratory evolutionary computation, followed by the presentation of two case studies focusing on the exemplary development of spatial envelope morphologies and urban block morphologies. (paper)

  17. Association between virulence and triazole tolerance in the phytopathogenic fungus Mycosphaerella graminicola.

    Directory of Open Access Journals (Sweden)

    Lina Yang

    Full Text Available Host resistance and synthetic antimicrobials such as fungicides are two of the main approaches used to control plant diseases in conventional agriculture. Although pathogens often evolve to overcome host resistance and antimicrobials, the majority of reports have involved qualitative host - pathogen interactions or antimicrobials targeting a single pathogen protein or metabolic pathway. Studies that consider jointly the evolution of virulence, defined as the degree of damage caused to a host by parasite infection, and antimicrobial resistance are rare. Here we compared virulence and fungicide tolerance in the fungal pathogen Mycosphaerella graminicola sampled from wheat fields across three continents and found a positive correlation between virulence and tolerance to a triazole fungicide. We also found that quantitative host resistance selected for higher pathogen virulence. The possible mechanisms responsible for these observations and their consequences for sustainable disease management are discussed.

  18. Invasive mold infections: virulence and pathogenesis of mucorales.

    Science.gov (United States)

    Morace, Giulia; Borghi, Elisa

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses.

  19. Invasive Mold Infections: Virulence and Pathogenesis of Mucorales

    Directory of Open Access Journals (Sweden)

    Giulia Morace

    2012-01-01

    Full Text Available Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses.

  20. Brucella, nitrogen and virulence.

    Science.gov (United States)

    Ronneau, Severin; Moussa, Simon; Barbier, Thibault; Conde-Álvarez, Raquel; Zuniga-Ripa, Amaia; Moriyon, Ignacio; Letesson, Jean-Jacques

    2016-08-01

    The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death, suggesting subtle but efficient use of host resources. Brucellae are amino-acid prototrophs able to grow with ammonium or use glutamate as the sole carbon-nitrogen source in vitro. They contain more than twice amino acid/peptide/polyamine uptake genes than the amino-acid auxotroph Legionella pneumophila, which multiplies in a similar vacuole, suggesting a different nutritional strategy. During these two last decades, many mutants of key actors in nitrogen metabolism (transporters, enzymes, regulators, etc.) have been described to be essential for full virulence of brucellae. Here, we review the genomic and experimental data on Brucella nitrogen metabolism and its connection with virulence. An analysis of various aspects of this metabolism (transport, assimilation, biosynthesis, catabolism, respiration and regulation) has highlighted differences and similarities in nitrogen metabolism with other α-Proteobacteria. Together, these data suggest that, during their intracellular life cycle, the brucellae use various nitrogen sources for biosynthesis, catabolism and respiration following a strategy that requires prototrophy and a tight regulation of nitrogen use.

  1. Natural variation in virulence of the entomopathogenic fungus Beauveria bassiana against malaria mosquitoes.

    Science.gov (United States)

    Valero-Jiménez, Claudio A; Debets, Alfons J M; van Kan, Jan A L; Schoustra, Sijmen E; Takken, Willem; Zwaan, Bas J; Koenraadt, Constantianus J M

    2014-12-06

    Insecticide resistance is greatly hampering current efforts to control malaria and therefore alternative methods are needed. Entomopathogenic fungi have been proposed as an alternative with a special focus on the cosmopolitan species Beauveria bassiana. However, few studies have analysed the effects of natural variation within fungal isolates on mosquito survival, and the implications and possible exploitation for malaria control. Laboratory bioassays were performed on adult female mosquitoes (Anopheles coluzzii) with spores from 29 isolates of B. bassiana, originating from different parts of the world. In addition, phenotypic characteristics of the fungal isolates such as sporulation, spore size and growth rate were studied to explore their relationship with virulence. All tested isolates of B. bassiana killed An. coluzzii mosquitoes, and the rate at which this happened differed significantly among the isolates. The risk of mosquitoes dying was around ten times higher when they were exposed to the most virulent as compared to the least virulent isolate. There was significant variation among isolates in spore size, growth rate and sporulation, but none of these morphological characteristics were correlated, and thus predictive, for the ability of the fungal isolate to kill malaria mosquitoes. This study shows that there is a wide natural variation in virulence of isolates of B. bassiana, and that selecting an appropriate fungal isolate is highly relevant in killing and thus controlling malaria mosquitoes, particularly if used as part of an integrated vector management strategy. Also, the wide variation observed in virulence offers the opportunity to better understand the molecular and genetic mechanisms that drive this variation and thus to address the potential development of resistance against entomopathogenic fungi.

  2. Fungal genomics beyond Saccharomyces cerevisiae?

    DEFF Research Database (Denmark)

    Hofmann, Gerald; Mcintyre, Mhairi; Nielsen, Jens

    2003-01-01

    Fungi are used extensively in both fundamental research and industrial applications. Saccharomyces cerevisiae has been the model organism for fungal research for many years, particularly in functional genomics. However, considering the diversity within the fungal kingdom, it is obvious...

  3. Fungal prostatitis: an update.

    Science.gov (United States)

    Mayayo, Emilio; Fernández-Silva, Fabiola

    2014-06-01

    Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

  4. Fungal Wound Infection

    Centers for Disease Control (CDC) Podcasts

    2016-01-28

    Dr. David Tribble, acting director of the infectious disease clinical research program at Uniformed Services University of the Health Sciences, discusses fungal wound infections after combat trauma.  Created: 1/28/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/28/2016.

  5. The Fungal Kingdom

    NARCIS (Netherlands)

    Heitman, Joseph; Howlett, B.J.; Crous, P.W.; Stukenbrock, E.H.; James, T.Y.; Gow, N.A.R.

    2017-01-01

    Fungi research and knowledge grew rapidly following recent advances in genetics and genomics. This book synthesizes new knowledge with existing information to stimulate new scientific questions and propel fungal scientists on to the next stages of research. This book is a comprehensive guide on

  6. Specific recognition of fungal pathogens by plants

    International Nuclear Information System (INIS)

    Knogge, W.; Gierlich, A.; Max-Planck-Institute for Plant Breeding,; Van't Slot, K.A.E.; Papavoine, T.

    2001-01-01

    Full text: Induction of plant defence reactions and, hence, genotype-specific disease resistance results from the interaction of highly specific plant resistance (R) genes with matching pathogen avirulence (Avr) genes (gene-for-gene interactions). More than thirty R genes acting against different types of pathogens (viruses, bacteria, fungi, oomycetes, nematodes) have been isolated from various plants species. However, with few exceptions it remains to be shown how their products recognise the complementary Avr gene products. To date, Avr genes and their products have been characterised from only three fungal species. These include the NIP1 gene from Rhynchosporium secalis, the causal agent of barley leaf scald. It encodes a small, secreted protein, NIP1, that triggers defence reactions exclusively in barley cultivars expressing the R gene Rrs1. NIP1 also non-specifically stimulates the H + -ATPase activity in barley plasma membranes, suggesting that the host recognition system targets a putative fungal virulence factor. Virulent fungal strains lack the gene or carry an allele encoding a non-functional product. Four NIP1 iso-forms have been characterised; NIP1-I and NIP1-II although both elicitor-active display different levels of activity, whereas the isoforms NIP1-III and NIP1-IV are inactive. After establishing a heterologous expression system, the single amino acids specifying NIP1-III and NIP1-IV were integrated into the NIP1-I sequence and yielded the inactive mutant proteins NIP1-III* and NIP1-IV*. The elicitor-inactive isoforms were also unable to stimulate the H + -ATPase, suggesting that both functions of NIP1 are mediated by a single plant receptor. The 3D structure of NIP1-I has been elucidated by 1 H- and 15 N-NMR spectroscopy. Binding studies using 125 I-NIP1-I revealed a single class of high-affinity binding sites on membranes from both Rrs1- and rrs1-cultivars, suggesting that NIP1-binding is not sufficient for defence triggering and that an

  7. Bone morphogenetic protein-2 and bone therapy: successes and pitfalls.

    Science.gov (United States)

    Poon, Bonnie; Kha, Tram; Tran, Sally; Dass, Crispin R

    2016-02-01

    Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy. The PubMed database was consulted to compile this review. With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects. Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery. © 2015 Royal Pharmaceutical Society.

  8. Role of bone morphogenetic protein-7 in renal fibrosis

    Directory of Open Access Journals (Sweden)

    Rui Xi eLi

    2015-04-01

    Full Text Available Renal fibrosis is final common pathway of end stage renal disease. Irrespective of the primary cause, renal fibrogenesis is a dynamic process which involves a large network of cellular and molecular interaction, including pro-inflammatory cell infiltration and activation, matrix-producing cell accumulation and activation, and secretion of profibrogenic factors that modulate extracellular matrix (ECM formation and cell-cell interaction. Bone morphogenetic protein-7 is a protein of the TGF-β super family and increasingly regarded as a counteracting molecule against TGF-β. A large variety of evidence shows an anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely mediated via counterbalancing the profibrotic effect of TGF-β. Besides, BMP-7 reduced ECM formation by inactivating matrix-producing cells and promoting mesenchymal-to-epithelial transition (MET. BMP-7 also increased ECM degradation. Despite these observations, the anti-fibrotic effect of BMP-7 is still controversial such that fine regulation of BMP-7 expression in vivo might be a great challenge for its ultimate clinical application.

  9. Simvastatin enhances bone morphogenetic protein receptor type II expression

    International Nuclear Information System (INIS)

    Hu Hong; Sung, Arthur; Zhao, Guohua; Shi, Lingfang; Qiu Daoming; Nishimura, Toshihiko; Kao, Peter N.

    2006-01-01

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function

  10. Role of bone morphogenetic protein-7 in renal fibrosis

    Science.gov (United States)

    Li, Rui Xi; Yiu, Wai Han; Tang, Sydney C. W.

    2015-01-01

    Renal fibrosis is final common pathway of end stage renal disease. Irrespective of the primary cause, renal fibrogenesis is a dynamic process which involves a large network of cellular and molecular interaction, including pro-inflammatory cell infiltration and activation, matrix-producing cell accumulation and activation, and secretion of profibrogenic factors that modulate extracellular matrix (ECM) formation and cell-cell interaction. Bone morphogenetic protein-7 is a protein of the TGF-β super family and increasingly regarded as a counteracting molecule against TGF-β. A large variety of evidence shows an anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely mediated via counterbalancing the profibrotic effect of TGF-β. Besides, BMP-7 reduced ECM formation by inactivating matrix-producing cells and promoting mesenchymal-to-epithelial transition (MET). BMP-7 also increased ECM degradation. Despite these observations, the anti-fibrotic effect of BMP-7 is still controversial such that fine regulation of BMP-7 expression in vivo might be a great challenge for its ultimate clinical application. PMID:25954203

  11. Virulence Factors of Streptococcus mutans.

    Science.gov (United States)

    1986-08-01

    763512/715242 Final Report U VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS U Samuel Rosen Department of Oral Biology For the Period April 1, 1983 - June 30...00 FINAL REPORT VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS Sam Rosen, Irving Shklair, E. X. Beck and F. M. Beck Ohio State University Columbus,Oh and...206-212. Johnson CP, Gorss S, Hillman JD (1978). Cariogenic properties of LDH deficient mutants of streptococcus mutans . J Dent Res 57, Special Issue

  12. Myco-fluidics: The fluid dynamics of fungal chimerism

    Science.gov (United States)

    Roper, Marcus; Hickey, Patrick; Dressaire, Emilie; Roch, Sebastien

    2012-11-01

    Chimeras-fantastical creatures formed as amalgams of many animals-have captured the human imagination since Ancient times. But they are also surprisingly common in Nature. The syncytial cells of filamentous fungi harbor large numbers of nuclei bathed in a single cytoplasm. As a fungus grows these nuclei become genetically diverse, either from mutation or from exchange of nuclei between different fungal individuals, a process that is known to increase the virulence of the fungus and its adaptability. By directly measuring nuclear movement in the model ascomycete fungus Neurospora crassa, we show that the fungus' tolerance for internal genetic diversity is enabled by hydrodynamic mixing of nuclei acting at all length scales within the fungal mycelium. Mathematical modeling and experiments in a mutant with altered mycelial morphology reveal some of the exquisite hydraulic engineering necessary to create these mixing flows from spatially coarse pressure gradients.

  13. [Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

    Science.gov (United States)

    Pemán, Javier; Salavert, Miguel

    2014-01-01

    The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. Copyright © 2014. Published by Elsevier Espana.

  14. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  15. Identification of O-mannosylated virulence factors in Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Alfonso Fernández-Álvarez

    Full Text Available The O-mannosyltransferase Pmt4 has emerged as crucial for fungal virulence in the animal pathogens Candida albicans or Cryptococcus neoformans as well as in the phytopathogenic fungus Ustilago maydis. Pmt4 O-mannosylates specific target proteins at the Endoplasmic Reticulum. Therefore a deficient O-mannosylation of these target proteins must be responsible for the loss of pathogenicity in pmt4 mutants. Taking advantage of the characteristics described for Pmt4 substrates in Saccharomyces cerevisiae, we performed a proteome-wide bioinformatic approach to identify putative Pmt4 targets in the corn smut fungus U. maydis and validated Pmt4-mediated glycosylation of candidate proteins by electrophoretic mobility shift assays. We found that the signalling mucin Msb2, which regulates appressorium differentiation upstream of the pathogenicity-related MAP kinase cascade, is O-mannosylated by Pmt4. The epistatic relationship of pmt4 and msb2 showed that both are likely to act in the same pathway. Furthermore, constitutive activation of the MAP kinase cascade restored appressorium development in pmt4 mutants, suggesting that during the initial phase of infection the failure to O-mannosylate Msb2 is responsible for the virulence defect of pmt4 mutants. On the other hand we demonstrate that during later stages of pathogenic development Pmt4 affects virulence independently of Msb2, probably by modifying secreted effector proteins. Pit1, a protein required for fungal spreading inside the infected leaf, was also identified as a Pmt4 target. Thus, O-mannosylation of different target proteins affects various stages of pathogenic development in U. maydis.

  16. Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

    Science.gov (United States)

    Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

    2017-01-01

    The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans’ replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal’s effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells

  17. Fungal dimorphism: the switch from hyphae to yeast is a specialized morphogenetic adaptation allowing colonization of a host.

    Science.gov (United States)

    Boyce, Kylie J; Andrianopoulos, Alex

    2015-11-01

    The ability of pathogenic fungi to switch between a multicellular hyphal and unicellular yeast growth form is a tightly regulated process known as dimorphic switching. Dimorphic switching requires the fungus to sense and respond to the host environment and is essential for pathogenicity. This review will focus on the role of dimorphism in fungi commonly called thermally dimorphic fungi, which switch to a yeast growth form during infection. This group of phylogenetically diverse ascomycetes includes Talaromyces marneffei (recently renamed from Penicillium marneffei), Blastomyces dermatitidis (teleomorph Ajellomyces dermatitidis), Coccidioides species (C. immitis and C. posadasii), Histoplasma capsulatum (teleomorph Ajellomyces capsulatum), Paracoccidioides species (P. brasiliensis and P. lutzii) and Sporothrix schenckii (teleomorph Ophiostoma schenckii). This review will explore both the signalling pathways regulating the morphological transition and the transcriptional responses necessary for intracellular growth. The physiological requirements of yeast cells during infection will also be discussed, highlighting recent advances in the understanding of the role of iron and calcium acquisition during infection. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. A Nitrogen Response Pathway Regulates Virulence Functions in Fusarium oxysporum via the Protein Kinase TOR and the bZIP Protein MeaB

    OpenAIRE

    López-Berges, Manuel S.; Rispail, Nicolas; Prados-Rosales, Rafael C.; Pietro, Antonio D.

    2010-01-01

    During infection, fungal pathogens activate virulence mechanisms, such as host adhesion, penetration and invasive growth. In the vascular wilt fungus Fusarium oxysporum, the mitogen-activated protein kinase Fmk1 is required for plant infection and controls processes such as cellophane penetration, vegetative hyphal fusion, or root adhesion. Here, we show that these virulence-related functions are repressed by the preferred nitrogen source ammonium and restored by treatment with l-methionine s...

  19. Strategies for delivering bone morphogenetic protein for bone healing

    Energy Technology Data Exchange (ETDEWEB)

    Begam, Howa [School of Bioscience and Engineering, Jadavpur University, Kolkata 700032 (India); Nandi, Samit Kumar, E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery, Radiology West Bengal University of Animal and Fishery Sciences, Kolkata 700037 (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata 700032 (India); Chanda, Abhijit [Department of Mechanical Engineering, Jadavpur University, Kolkata 700032 (India)

    2017-01-01

    Bone morphogenetic proteins (BMPs) are the most significant growth factors that belong to the Transforming Growth Factor Beta (TGF-β) super-family. Though more than twenty members of this family have been identified so far in humans, Food and Drug Administration (FDA) approved two growth factors: BMP-2 and BMP-7 for treatments of spinal fusion and long-bone fractures with collagen carriers. Currently BMPs are clinically used in spinal fusion, oral and maxillofacial surgery and also in the repair of long bone defects. The efficiency of BMPs depends a lot on the selection of suitable carriers. At present, different types of carrier materials are used: natural and synthetic polymers, calcium phosphate and ceramic-polymer composite materials. Number of research articles has been published on the minute intricacies of the loading process and release kinetics of BMPs. Despite the significant evidence of its potential for bone healing demonstrated in animal models, future clinical investigations are needed to define dose, scaffold and route of administration. The efficacy and application of BMPs in various levels with a proper carrier and dose is yet to be established. The present article collates various aspects of success and limitation and identifies the prospects and challenges associated with the use of BMPs in orthopaedic surgery. - Highlights: • Currently BMPs are clinically used in spinal fusion, oral and maxillofacial surgery and also in repair of long bone defects. • Different types of carrier materials are used: natural, synthetic polymers, calcium phosphate and ceramic-polymer composite • Efficacy and application of BMPs in various levels with proper carrier and dose is yet to be established • Number of research articles has been published on minute intricacies of loading process and release kinetics of BMPs • Present article collates success, limitation and identifies prospects, challenges for use of BMPs in orthopaedic surgery.

  20. Regulation of bone morphogenetic proteins in early embryonic development

    Science.gov (United States)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  1. Bone morphogenetic proteins: from structure to clinical use

    Directory of Open Access Journals (Sweden)

    Granjeiro J.M.

    2005-01-01

    Full Text Available Bone morphogenetic proteins (BMPs are multi-functional growth factors belonging to the transforming growth factor ß superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases.

  2. Promotion of bone morphogenetic protein signaling by tetraspanins and glycosphingolipids.

    Directory of Open Access Journals (Sweden)

    Zhiyu Liu

    2015-05-01

    Full Text Available Bone morphogenetic proteins (BMPs belong to the transforming growth factor β (TGFβ superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes in metazoans. Malfunction of the BMP pathway can cause a variety of diseases in humans, including cancer, skeletal disorders and cardiovascular diseases. Identification of factors that ensure proper spatiotemporal control of BMP signaling is critical for understanding how this pathway is regulated. We have used a unique and sensitive genetic screen to identify the plasma membrane-localized tetraspanin TSP-21 as a key new factor in the C. elegans BMP-like "Sma/Mab" signaling pathway that controls body size and postembryonic M lineage development. We showed that TSP-21 acts in the signal-receiving cells and genetically functions at the ligand-receptor level. We further showed that TSP-21 can associate with itself and with two additional tetraspanins, TSP-12 and TSP-14, which also promote Sma/Mab signaling. TSP-12 and TSP-14 can also associate with SMA-6, the type I receptor of the Sma/Mab pathway. Finally, we found that glycosphingolipids, major components of the tetraspanin-enriched microdomains, are required for Sma/Mab signaling. Our findings suggest that the tetraspanin-enriched membrane microdomains are important for proper BMP signaling. As tetraspanins have emerged as diagnostic and prognostic markers for tumor progression, and TSP-21, TSP-12 and TSP-14 are all conserved in humans, we speculate that abnormal BMP signaling due to altered expression or function of certain tetraspanins may be a contributing factor to cancer development.

  3. Induction of MAP Kinase Homologues during Growth and Morphogenetic Development of Karnal Bunt (Tilletia indica) under the Influence of Host Factor(s) from Wheat Spikes

    Science.gov (United States)

    Gupta, Atul K.; Seneviratne, J. M.; Joshi, G. K.; Kumar, Anil

    2012-01-01

    Signaling pathways that activate different mitogen-activated protein kinases (MAPKs) in response to certain environmental conditions, play important role in mating type switching (Fus3) and pathogenicity (Pmk1) in many fungi. In order to determine the roles of such regulatory genes in Tilletia indica, the causal pathogen of Karnal bunt (KB) of wheat, semi-quantitative and quantitative RT-PCR was carried out to isolate and determine the expression of MAP kinase homologues during fungal growth and development under in vitro culture. Maximum expression of TiFus3 and TiPmk1 genes were observed at 14th and 21st days of culture and decreased thereafter. To investigate whether the fungus alters the expression levels of same kinases upon interaction with plants, cultures were treated with 1% of host factors (extracted from S-2 stage of wheat spikes). Such treatment induced the expression of MAPks in time dependent manner compared to the absence of host factors. These results suggest that host factor(s) provide certain signal(s) which activate TiFus3 and TiPmk1 during morphogenetic development of T. indica. The results also provides a clue about the role of host factors in enhancing the disease potential due to induction of MAP kinases involved in fungal development and pathogenecity. PMID:22547988

  4. The rebirth of the morphogenetic field as an explanatory tool in biology

    Directory of Open Access Journals (Sweden)

    Perović Slobodan

    2013-01-01

    Full Text Available I discuss two uses of the concept of the morphogenetic field, a tool of the 19th century biology motivated by particular ontological views of the time, which has been re-emerging and increasingly relevant in explaining microbiological phenomena. I also consider the relation of these uses to the Central Dogma of modern biology as well as Modern Synthesis of Darwinism and genetics. An induced morphogenetic field is determined by a physical (e.g., gravitational field, or it acquires a physical (e.g., visco-elastic field’s characteristics. Such a morphogenetic field presents only a weak challenge to the Central Dogma of Modern Synthesis by indirectly, albeit severely, constraining variability at the molecular level. I discuss explanations that introduce structural inheritance in ciliate protozoa, as well as the experimental evidence on which these arguments are based. The global cellular morphogenetic field is a unit of such inheritance. I discuss relevant cases of structural inheritance in ciliates that bring about internal cellular as well as functional changes and point out that DNA is absent in the cortex and that RNA controls neither intermediary nor the global level of the field. I go on to argue that utilizing knowledge of known physical fields may advance explanations and understanding of the morphogenetic field in ciliates as the unit of both development and inheritance. [Projekat Ministarstva nauke Republike Srbije, br. 179041: Dynamic Systems in nature and society: Philosophical and empirical aspects

  5. Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence

    OpenAIRE

    Li, Cecilia; Lev, Sophie; Saiardi, Adolfo; Desmarini, Desmarini; Sorrell, Tania C.; Djordjevic, Julianne T.

    2016-01-01

    Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1?), and in combination with KCS1 (ipk1?kcs1?), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenua...

  6. Fungal biodiversity to biotechnology.

    Science.gov (United States)

    Chambergo, Felipe S; Valencia, Estela Y

    2016-03-01

    Fungal habitats include soil, water, and extreme environments. With around 100,000 fungus species already described, it is estimated that 5.1 million fungus species exist on our planet, making fungi one of the largest and most diverse kingdoms of eukaryotes. Fungi show remarkable metabolic features due to a sophisticated genomic network and are important for the production of biotechnological compounds that greatly impact our society in many ways. In this review, we present the current state of knowledge on fungal biodiversity, with special emphasis on filamentous fungi and the most recent discoveries in the field of identification and production of biotechnological compounds. More than 250 fungus species have been studied to produce these biotechnological compounds. This review focuses on three of the branches generally accepted in biotechnological applications, which have been identified by a color code: red, green, and white for pharmaceutical, agricultural, and industrial biotechnology, respectively. We also discuss future prospects for the use of filamentous fungi in biotechnology application.

  7. A plant pathology perspective of fungal genome sequencing.

    Science.gov (United States)

    Aylward, Janneke; Steenkamp, Emma T; Dreyer, Léanne L; Roets, Francois; Wingfield, Brenda D; Wingfield, Michael J

    2017-06-01

    The majority of plant pathogens are fungi and many of these adversely affect food security. This mini-review aims to provide an analysis of the plant pathogenic fungi for which genome sequences are publically available, to assess their general genome characteristics, and to consider how genomics has impacted plant pathology. A list of sequenced fungal species was assembled, the taxonomy of all species verified, and the potential reason for sequencing each of the species considered. The genomes of 1090 fungal species are currently (October 2016) in the public domain and this number is rapidly rising. Pathogenic species comprised the largest category (35.5 %) and, amongst these, plant pathogens are predominant. Of the 191 plant pathogenic fungal species with available genomes, 61.3 % cause diseases on food crops, more than half of which are staple crops. The genomes of plant pathogens are slightly larger than those of other fungal species sequenced to date and they contain fewer coding sequences in relation to their genome size. Both of these factors can be attributed to the expansion of repeat elements. Sequenced genomes of plant pathogens provide blueprints from which potential virulence factors were identified and from which genes associated with different pathogenic strategies could be predicted. Genome sequences have also made it possible to evaluate adaptability of pathogen genomes and genomic regions that experience selection pressures. Some genomic patterns, however, remain poorly understood and plant pathogen genomes alone are not sufficient to unravel complex pathogen-host interactions. Genomes, therefore, cannot replace experimental studies that can be complex and tedious. Ultimately, the most promising application lies in using fungal plant pathogen genomics to inform disease management and risk assessment strategies. This will ultimately minimize the risks of future disease outbreaks and assist in preparation for emerging pathogen outbreaks.

  8. Current management of fungal infections.

    NARCIS (Netherlands)

    Meis, J.F.G.M.; Verweij, P.E.

    2001-01-01

    The management of superficial fungal infections differs significantly from the management of systemic fungal infections. Most superficial infections are treated with topical antifungal agents, the choice of agent being determined by the site and extent of the infection and by the causative organism,

  9. The evolution of fungal epiphytes

    NARCIS (Netherlands)

    Hongsanan, S.; Sánchez-Ramírez, S.; Crous, P.W.; Ariyawansa, H.A.; Zhao, R.L.; Hyde, K.D.

    2016-01-01

    Fungal epiphytes are a polyphyletic group found on the surface of plants, particularly on leaves, with a worldwide distribution. They belong in the phylum Ascomycota, which contains the largest known number of fungal genera. There has been little research dating the origins of the common ancestors

  10. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. Fifty-four adult male Wistar rats were randomly

  11. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats

  12. Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation

    NARCIS (Netherlands)

    Croes, M.; Kruyt, M. C.; Groen, W. M.; Van Dorenmalen, K. M.A.; Dhert, W. J.A.; Öner, F. C.; Alblas, J.

    2018-01-01

    Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is

  13. Potential role of centrioles in determining the morphogenetic status of animal somatic cells.

    Science.gov (United States)

    Tkemaladze, J; Chichinadze, K

    2005-05-01

    Irreversible differentiation (change of morphogenetic status) and programmed death (apoptosis) are observed only in somatic cells. Cell division is the only way by which the morphogenetic status of the offspring cells may be modified. It is known that there is a fixed limit to the number of possible cell divisions, the so-called 'Hayflick limit'. Existing links between cell division, differentiation and apoptosis make it possible to conclude that all these processes could be controlled by a single self-reproducing structure. Potential candidates for this replicable structure in a somatic cell are chromosomes, mitochondria (both contain DNA), and centrioles. Centrioles (diplosome) are the most likely unit that can fully regulate the processes of irreversible differentiation, determination and modification of the morphogenetic status. It may contain differently encoded RNA molecules stacked in a definite order. During mitosis, these RNA molecules are released one by one into the cytoplasm. In the presence of reverse transcriptase and endonuclease, RNA can be embedded in nuclear DNA. This process presumably changes the status of repressed and potentially active genes and, subsequently, the morphogenetic status of a cell.

  14. Case Study: Organotypic human in vitro models of embryonic morphogenetic fusion

    Science.gov (United States)

    Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell...

  15. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); J.C. van den Beukel (Anneke); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

    2015-01-01

    textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

  16. Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine

    NARCIS (Netherlands)

    Brouns, M.R.; Afman, L.A.; VanHauten, B.A.M.; Hekking, J.W.M.; Kohler, E.S.; Straaten, van H.W.M.

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed.

  17. Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine.

    NARCIS (Netherlands)

    Brouns, M.R.; Afman, L.A.; Vanhauten, B.A.M.; Hekking, J.W.M.; Köhler, E.S.; Straaten, H.W.M. van

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed.

  18. A novel method for standardized application of fungal spore coatings for mosquito exposure bioassays.

    Science.gov (United States)

    Farenhorst, Marit; Knols, Bart G J

    2010-01-20

    was suitable for evaluating fungal infectivity and virulence, allowing optimizations of spore dose and exposure time. Use of this standardized application method will help achieve reliable results that are exchangeable between different laboratories.

  19. A novel method for standardized application of fungal spore coatings for mosquito exposure bioassays

    Directory of Open Access Journals (Sweden)

    Knols Bart GJ

    2010-01-01

    with accurate effective spore concentrations. The mosquito bioassay was suitable for evaluating fungal infectivity and virulence, allowing optimizations of spore dose and exposure time. Use of this standardized application method will help achieve reliable results that are exchangeable between different laboratories.

  20. Superficial fungal infections.

    Science.gov (United States)

    Schwartz, Robert A

    Superficial fungal infections arise from a pathogen that is restricted to the stratum corneum, with little or no tissue reaction. In this Seminar, three types of infection will be covered: tinea versicolor, piedra, and tinea nigra. Tinea versicolor is common worldwide and is caused by Malassezia spp, which are human saprophytes that sometimes switch from yeast to pathogenic mycelial form. Malassezia furfur, Malassezia globosa, and Malassezia sympodialis are most closely linked to tinea versicolor. White and black piedra are both common in tropical regions of the world; white piedra is also endemic in temperate climates. Black piedra is caused by Piedraia hortae; white piedra is due to pathogenic species of the Trichosporon genus. Tinea nigra is also common in tropical areas and has been confused with melanoma.

  1. Fungal keratitis: A review

    International Nuclear Information System (INIS)

    Jastaneiah, Sabah S.; Al-Rajhi, Ali A.

    2006-01-01

    Keratomycosis is a vision-threatening fungal corneal infection. The dramatic increase in the number of cases over the past three decades is attributable not only to better diagnostic recognition, improved laboratory techniques and greater awareness by the ophthalmic society as a whole, but is also due to a true increase in the incidence of keratitis related to the indiscriminate use of topical broad-spectrum antibiotics, corticosteroids and immunosuppressive drugs, as well as surgical trauma. Corneal trauma has remained the main predisposing factor over the years, though in recent years HIV-positive cases and AIDS are taking lead in certain areas. Aspergillus, Fusarium and Candida species remains the commonest 'organisms' isolated worldwide. Although the approach to this form of keratitis is similar to other types of microbial keratitis, it remains the most difficult in terms of diagnosis and management. Early recognition, prevention, prompt treatment and timely keratoplasty are crucial for a better outcome. (author)

  2. Fungal melanins and their interactions with metals.

    Science.gov (United States)

    Fogarty, R V; Tobin, J M

    1996-09-01

    Fungal melanins are dark brown or black pigments located in cell walls. They also exist as extracellular polymers. Melanized fungi possess increased virulence and resistance to microbial attack as well as enhanced survival while under environmental stress. Melanins contain various functional groups which provide an array of multiple nonequivalent binding sites for metal ions. Pigmented Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu, Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher rates. Metal desorption was significantly lower for extracellular melanin than from pigmented or albino biomass which indicated the strength of the melanin-metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM, pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7 mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an equilibrium concentration of only 0.4 mM. Addition of melanin to the growth medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding and sequestration.

  3. Aspergillus fumigatus mitochondrial electron transport chain mediates oxidative stress homeostasis, hypoxia responses and fungal pathogenesis.

    Science.gov (United States)

    Grahl, Nora; Dinamarco, Taisa Magnani; Willger, Sven D; Goldman, Gustavo H; Cramer, Robert A

    2012-04-01

    We previously observed that hypoxia is an important component of host microenvironments during pulmonary fungal infections. However, mechanisms of fungal growth in these in vivo hypoxic conditions are poorly understood. Here, we report that mitochondrial respiration is active in hypoxia (1% oxygen) and critical for fungal pathogenesis. We generated Aspergillus fumigatus alternative oxidase (aoxA) and cytochrome C (cycA) null mutants and assessed their ability to tolerate hypoxia, macrophage killing and virulence. In contrast to ΔaoxA, ΔcycA was found to be significantly impaired in conidia germination, growth in normoxia and hypoxia, and displayed attenuated virulence. Intriguingly, loss of cycA results in increased levels of AoxA activity, which results in increased resistance to oxidative stress, macrophage killing and long-term persistence in murine lungs. Thus, our results demonstrate a previously unidentified role for fungal mitochondrial respiration in the pathogenesis of aspergillosis, and lay the foundation for future research into its role in hypoxia signalling and adaptation. © 2012 Blackwell Publishing Ltd.

  4. Host-Pathogen Interactions: I. A Correlation Between α-Galactosidase Production and Virulence 1

    Science.gov (United States)

    English, Patricia D.; Albersheim, Peter

    1969-01-01

    Resistance or susceptibility of Red Kidney, Pinto and Small White beans (Phaseolus vulgaris) to the alpha, beta, and gamma strains of Colletotrichum lindemuthianum was either confirmed or established. These fungal strains secrete α-galactosidase, β-galactosidase and β-xylosidase when grown on cell walls isolated from the hypocotyls of any of the above bean varieties. These enzymes effectively degrade cell walls isolated from susceptible 5-day old hypocotyls but degrade only slightly the walls isolated from resistant 18-day old hypocotyls. The amounts of the β-galactosidase and β-xylosidase secreted by the 3 fungal strains are relatively low and are approximately equivalent. The secretion of these 2 enzymes is not dependent upon the bean variety from which the hypocotyl cell walls used as a carbon source were isolated. However, the fungal strains secrete greater amounts of α-galactosidase when grown on hypocotyl cell walls isolated from susceptible plants than when grown on walls from resistant plants. Virulent isolates of the fungus, when grown on hypocotyl cell walls isolated from a susceptible plant, secrete more α-galactosidase than do attenuated (avirulent) isolates of the same fungal strain grown under the same conditions. The α-galactosidase secreted by each of the fungal strains is capable of removing galactose from the hypocotyl cell walls of each bean variety tested. Galactose is removed from the cell walls of each variety at the same rate regardless of whether the cell walls were isolated from a susceptible or resistant plant. PMID:16657049

  5. Anaerobic fungal populations

    International Nuclear Information System (INIS)

    Brookman, J.L.; Nicholson, M.J.

    2005-01-01

    The development of molecular techniques has greatly broadened our view of microbial diversity and enabled a more complete detection and description of microbial communities. The application of these techniques provides a simple means of following community changes, for example, Ishii et al. described transient and more stable inhabitants in another dynamic microbial system, compost. Our present knowledge of anaerobic gut fungal population diversity within the gastrointestinal tract is based upon isolation, cultivation and observations in vivo. It is likely that there are many species yet to be described, some of which may be non-culturable. We have observed a distinct difference in the ease of cultivation between the different genera, for example, Caecomyes isolates are especially difficult to isolate and maintain in vitro, a feature that is likely to result in the under representation of this genera in culture-based enumerations. The anaerobic gut fungi are the only known obligately anaerobic fungi. For the majority of their life cycles, they are found tightly associated with solid digesta in the rumen and/or hindgut. They produce potent fibrolytic enzymes and grow invasively on and into the plant material they are digesting making them important contributors to fibre digestion. This close association with intestinal digesta has made it difficult to accurately determine the amount of fungal biomass present in the rumen, with Orpin suggesting 8% contribution to the total microbial biomass, whereas Rezaeian et al. more recently gave a value of approximately 20%. It is clear that the rumen microbial complement is affected by dietary changes, and that the fungi are more important in digestion in the rumens of animals fed with high-fibre diets. It seems likely that the gut fungi play an important role within the rumen as primary colonizers of plant fibre, and so we are particularly interested in being able to measure the appearance and diversity of fungi on the plant

  6. Short Rotations in Forest Plantations Accelerate Virulence Evolution in Root-Rot Pathogenic Fungi

    Directory of Open Access Journals (Sweden)

    Jean-Paul Soularue

    2017-06-01

    Full Text Available As disease outbreaks in forest plantations are causing concern worldwide, a clear understanding of the influence of silvicultural practices on the development of epidemics is still lacking. Importantly, silvicultural practices are likely to simultaneously affect epidemiological and evolutionary dynamics of pathogen populations. We propose a genetically explicit and individual-based model of virulence evolution in a root-rot pathogenic fungus spreading across forest landscapes, taking the Armillaria ostoyae–Pinus pinaster pathosystem as reference. We used the model to study the effects of rotation length on the evolution of virulence and the propagation of the fungus within a forest landscape composed of even-aged stands regularly altered by clear-cutting and thinning operations. The life cycle of the fungus modeled combines asexual and sexual reproduction modes, and also includes parasitic and saprotrophic phases. Moreover, the tree susceptibility to the pathogen is primarily determined by the age of the stand. Our simulations indicated that the shortest rotation length accelerated both the evolution of virulence and the development of the epidemics, whatever the genetic variability in the initial fungal population and the asexuality rate of the fungal species

  7. Hospitalized Patients and Fungal Infections

    Science.gov (United States)

    ... are mild skin rashes, but others can be deadly, like fungal pneumonia. Because of this, it’s important ... the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on ...

  8. Cancer Patients and Fungal Infections

    Science.gov (United States)

    ... are mild skin rashes, but others can be deadly, like fungal pneumonia. Because of this, it’s important ... the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on ...

  9. Salmonella-secreted Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  10. The impact of the postharvest environment on the viability and virulence of decay fungi.

    Science.gov (United States)

    Liu, Jia; Sui, Yuan; Wisniewski, Michael; Xie, Zhigang; Liu, Yiqing; You, Yuming; Zhang, Xiaojing; Sun, Zhiqiang; Li, Wenhua; Li, Yan; Wang, Qi

    2018-07-03

    Postharvest decay of fruits, vegetables, and grains by fungal pathogens causes significant economic losses. Infected produce presents a potential health risk since some decay fungi produce mycotoxins that are hazardous to human health. Infections are the result of the interplay between host resistance and pathogen virulence. Both of these processes, however, are significantly impacted by environmental factors, such as temperature, UV, oxidative stress, and water activity. In the present review, the impact of various physical postharvest treatments (e.g., heat and UV) on the viability and virulence of postharvest pathogens is reviewed and discussed. Oxidative injury, protein impairment, and cell wall degradation have all been proposed as the mechanisms by which these abiotic stresses reduce fungal viability and pathogenicity. The response of decay fungi to pH and the ability of pathogens to modulate the pH of the host environment also affect pathogenicity. The effects of the manipulation of the postharvest environment by ethylene, natural edible coatings, and controlled atmosphere storage on fungal viability are also discussed. Lastly, avenues of future research are proposed.

  11. Structural Analysis of Fungal Cerebrosides

    Directory of Open Access Journals (Sweden)

    Eliana eBarreto-Bergter

    2011-12-01

    Full Text Available Of the ceramide monohexosides (CMHs, gluco- and galactosylceramides are the main neutral glycosphingolipids expressed in fungal cells. Their structural determination is greatly dependent on the use of mass spectrometric techniques, including fast atom bombardment-mass spectrometry (FAB-MS, electrospray ionization (ESI-MS, and energy collision-induced dissociation mass spectrometry (ESI-MS/CID-MS. Nuclear magnetic resonance (NMR has also been used successfully. Such a combination of techniques, combined with classical analytical separation, such as HPTLC and column chromatography, has led to the structural elucidation of a great number of fungal CMHs. The structure of fungal CMH is conserved among fungal species and consists of a glucose or galactose residue attached to a ceramide moiety containing 9-methyl-4,8-sphingadienine with an amidic linkage to hydroxylated fatty acids, most commonly having 16 or 18 carbon atoms and unsaturation between C-3 and C-4. Along with their unique structural characteristics, fungal CMHs have a peculiar subcellular distribution and striking biological properties. Fungal cerebrosides were also characterized as antigenic molecules directly or indirectly involved in cell growth or differentiation in Schizophyllum commune, Cryptococcus neoformans, Pseudallescheria boydii, Candida albicans, Aspergillus nidulans, A.fumigatus and Colletotrichum gloeosporioides. Besides classical techniques for cerebroside (CMH analysis, we now describe new approaches, combining conventional TLC and mass spectrometry, as well as emerging technologies for subcellular localization and distribution of glycosphingolipids by SIMS and imaging MALDI TOF .

  12. Serious fungal infections in Ecuador.

    Science.gov (United States)

    Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M

    2017-06-01

    There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (Ecuador is affected by serious fungal infection.

  13. Artemisia sieberi Besser essential oil and treatment of fungal infections.

    Science.gov (United States)

    Mahboubi, Mohaddese

    2017-05-01

    A. sieberi essential oil has been used for treatment of hardly curable infectious ulcers in Middle East Medicine and has been famous due to its wormicide effects. In this review, we evaluated the potency of A. sieberi essential oil in treatment of fungal infections. We searched in PubMed Central, Science direct, Wiley, Springer, SID, and accessible books, reports, thesis. There is a lot of mixed information on chemical compositions of A. sieberi essential oil, but most articles reported α, β-thujones as the main components of essential oils. In vitro studies confirmed the antifungal activity of A. sieberi essential oil against saprophytes fungi, dermatophytes, Malassezia sp. and Candida sp. and these results were confirmed in six clinical studies. The clinical studies confirmed the superiority of A. sieberi essential oil (5%) lotion in improvement of clinical signs of fungal superficial diseases, and mycological laboratory examinations of dermatophytosis and pityriasis versicolor diseases than clotrimazole (1%) topical treatment. The recurrence rate of superficial fungal infections with dermatophytosis and pityriasis versicolor was statistically lower in A. sieberi essential oil (5%) lotion than clotrimazole. There are no adverse effects due to the application of A. sieberi essential oil in clinical studies. Despite, the efficacy of A. sieberi essential oil against Candida sp., there is no clinical study about their related infections. Investigation about the effects of A. sieberi essential oil on fungal virulence factors in order to identifying the exact mechanism of antifungal activity and clinical trials on Candida related diseases are recommended. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Helicobacter pylori virulence and cancer pathogenesis.

    Science.gov (United States)

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  15. Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis

    DEFF Research Database (Denmark)

    Zhang, Hongbin; Schulz, Tim J; Espinoza, Daniel O

    2010-01-01

    Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin...... BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance....

  16. Morphogenetic movements during cranial neural tube closure in the chick embryo and the effect of homocysteine

    OpenAIRE

    Brouns, M.R.; Afman, L.A.; VanHauten, B.A.M.; Hekking, J.W.M.; Kohler, E.S.; Straaten, van, H.W.M.

    2005-01-01

    In order to unravel morphogenetic mechanisms involved in neural tube closure, critical cell movements that are fundamental to remodelling of the cranial neural tube in the chick embryo were studied in vitro by quantitative time-lapse video microscopy. Two main directions of movements were observed. The earliest was directed medially; these cells invaginated into a median groove and were the main contributors to the initial neural tube closure. Once the median groove was completed, cells chang...

  17. Genome structure and reproductive behaviour influence the evolutionary potential of a fungal phytopathogen.

    Directory of Open Access Journals (Sweden)

    Guillaume Daverdin

    Full Text Available Modern agriculture favours the selection and spread of novel plant diseases. Furthermore, crop genetic resistance against pathogens is often rendered ineffective within a few years of its commercial deployment. Leptosphaeria maculans, the cause of phoma stem canker of oilseed rape, develops gene-for-gene interactions with its host plant, and has a high evolutionary potential to render ineffective novel sources of resistance in crops. Here, we established a four-year field experiment to monitor the evolution of populations confronted with the newly released Rlm7 resistance and to investigate the nature of the mutations responsible for virulence against Rlm7. A total of 2551 fungal isolates were collected from experimental crops of a Rlm7 cultivar or a cultivar without Rlm7. All isolates were phenotyped for virulence and a subset was genotyped with neutral genetic markers. Virulent isolates were investigated for molecular events at the AvrLm4-7 locus. Whilst virulent isolates were not found in neighbouring crops, their frequency had reached 36% in the experimental field after four years. An extreme diversity of independent molecular events leading to virulence was identified in populations, with large-scale Repeat Induced Point mutations or complete deletion of AvrLm4-7 being the most frequent. Our data suggest that increased mutability of fungal genes involved in the interactions with plants is directly related to their genomic environment and reproductive system. Thus, rapid allelic diversification of avirulence genes can be generated in L. maculans populations in a single field provided that large population sizes and sexual reproduction are favoured by agricultural practices.

  18. Bone Morphogenetic Protein Coating on Titanium Implant Surface: a Systematic Review

    Directory of Open Access Journals (Sweden)

    Haim Haimov

    2017-06-01

    Full Text Available Objectives: The purpose of the study is to systematically review the osseointegration process improvement by bone morphogenetic protein coating on titanium implant surface. Material and Methods: An electronic literature search was conducted through the MEDLINE (PubMed and EMBASE databases. The search was restricted for articles published during the last 10 years from October 2006 to September 2016 and articles were limited to English language. Results: A total of 41 articles were reviewed, and 8 of the most relevant articles that are suitable to the criteria were selected. Articles were analysed regarding concentration of bone morphogenetic protein (BMP, delivery systems, adverse reactions and the influence of the BMP on the bone and peri-implant surface in vivo. Finally, the present data included 340 implants and 236 models. Conclusions: It’s clearly shown from most of the examined studies that bone morphogenetic protein increases bone regeneration. Further studies should be done in order to induce and sustain bone formation activity. Osteogenic agent should be gradually liberated and not rapidly released with priority to three-dimension reservoir (incorporated titanium implant surface in order to avoid following severe side effects: inflammation, bleeding, haematoma, oedema, erythema, and graft failure.

  19. Evaluation of pulmonary fungal diseases in patients with fungal rhino-sinusitis

    Directory of Open Access Journals (Sweden)

    M.Sh. Badawy

    2013-07-01

    Conclusion: Universal screening for pulmonary fungal infection especially in patients with fungal rhino sinusitis is highly recommended to treat it early, decrease morbidity and mortality of the diseases.

  20. Phenotypic Characteristics Associated with Virulence of Clinical Isolates from the Sporothrix Complex

    Science.gov (United States)

    Almeida-Paes, Rodrigo; de Oliveira, Luã Cardoso; Oliveira, Manoel Marques Evangelista; Gutierrez-Galhardo, Maria Clara; Nosanchuk, Joshua Daniel; Zancopé-Oliveira, Rosely Maria

    2015-01-01

    The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis. PMID:25961005

  1. Emerging fungal diseases: the importance of the host.

    Science.gov (United States)

    Procop, Gary W; Roberts, Glenn D

    2004-09-01

    More yeasts and molds are now recognized to cause more human disease than ever before. This development is not due to a change in the virulence of these fungi, but rather to changes in the human host. These changes include immunosuppression secondary to the pandemic of HIV, the use of life-saving advances in chemotherapy and organ transplantation, and the use of corticosteroids and other immunosuppressive agents to treat a variety of diseases. Fungi that were once considered common saprophytes are now recognized as potential pathogens in these patients. This situation necessitates better communication than ever between the clinician, pathologist, and clinical mycologist to ensure the prompt and accurate determination of the cause of fungal diseases.

  2. Microbiological diagnostics of fungal infections

    Directory of Open Access Journals (Sweden)

    Corrado Girmenia

    2013-07-01

    Full Text Available Laboratory tests for the detection of fungal infections are easy to perform. The main obstacle to a correct diagnosis is the correlation between the laboratory findings and the clinical diagnosis. Among pediatric patients, the most common fungal pathogen is Candida. The detection of fungal colonization may be performed through the use of chromogenic culture media, which allows also the identification of Candida subspecies, from which pathogenicity depends. In neonatology, thistest often drives the decision to begin a empiric therapy; in this regard, a close cooperation between microbiologists and clinicians is highly recommended. Blood culture, if positive, is a strong confirmation of fungal infection; however, its low sensitivity results in a high percentage of false negatives, thus decreasing its reliability. Molecular diagnostics is still under evaluation, whereas the detection of some fungal antigens, such as β-D-glucan, galactomannan, mannoprotein, and cryptococcal antigen in the serum is used for adults, but still under evaluations for pediatric patients.http://dx.doi.org/10.7175/rhc.v4i1S.862

  3. Prophenoloxidase-Mediated Ex Vivo Immunity to Delay Fungal Infection after Insect Ecdysis

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2017-11-01

    Full Text Available Skin immunity protects animals from airborne pathogen infection. Unlike mammals, arthropods, including insects, undergo periodic ecdysis to grow and develop. Newly molted insects emerge with unsclerotized thin cuticles but successfully escape pathogenic infections during the post-molt period. Here we show that prophenoloxidases (PPOs in molting fluids remain bioactive on the integument and impede fungal infection after ecdysis. We found that the purified plasma PPOs or recombinant PPOs could effectively bind to fungal spores (conidia by targeting the cell wall components chitin and β-1,3-glucan. Pretreatment of the spores of the fungal pathogen Beauveria bassiana with PPOs increased spore hydrophilicity and reduced spore adhesion activity, resulting in a significant decrease in virulence as compared with mock infection. We also identified a spore-secreted protease BPS8, a member of peptidase S8 family of protease that degrade PPOs at high levels to benefit fungal infection, but which at lower doses activate PPOs to inhibit spore germination after melanization. These data indicate that insects have evolved a distinct strategy of ex vivo immunity to survive pathogen infections after ecdysis using PPOs in molting fluids retained on the underdeveloped and tender integument of newly molted insects for protection against airborne fungal infection.

  4. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang, E-mail: louhongxiang@sdu.edu.cn

    2017-05-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  5. Niche-Specific Requirement for Hyphal Wall protein 1 in Virulence of Candida albicans

    Science.gov (United States)

    Staab, Janet F.; Datta, Kausik; Rhee, Peter

    2013-01-01

    Specialized Candida albicans cell surface proteins called adhesins mediate binding of the fungus to host cells. The mammalian transglutaminase (TG) substrate and adhesin, Hyphal wall protein 1 (Hwp1), is expressed on the hyphal form of C. albicans where it mediates fungal adhesion to epithelial cells. Hwp1 is also required for biofilm formation and mating thus the protein functions in both fungal-host and self-interactions. Hwp1 is required for full virulence of C. albicans in murine models of disseminated candidiasis and of esophageal candidiasis. Previous studies correlated TG activity on the surface of oral epithelial cells, produced by epithelial TG (TG1), with tight binding of C. albicans via Hwp1 to the host cell surfaces. However, the contribution of other Tgs, specifically tissue TG (TG2), to disseminated candidiasis mediated by Hwp1 was not known. A newly created hwp1 null strain in the wild type SC5314 background was as virulent as the parental strain in C57BL/6 mice, and virulence was retained in C57BL/6 mice deleted for Tgm2 (TG2). Further, the hwp1 null strains displayed modestly reduced virulence in BALB/c mice as did strain DD27-U1, an independently created hwp1Δ/Δ in CAI4 corrected for its ura3Δ defect at the URA3 locus. Hwp1 was still needed to produce wild type biofilms, and persist on murine tongues in an oral model of oropharyngeal candidiasis consistent with previous studies by us and others. Finally, lack of Hwp1 affected the translocation of C. albicans from the mouse intestine into the bloodstream of mice. Together, Hwp1 appears to have a minor role in disseminated candidiasis, independent of tissue TG, but a key function in host- and self-association to the surface of oral mucosa. PMID:24260489

  6. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    International Nuclear Information System (INIS)

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang

    2017-01-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  7. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

    OpenAIRE

    McCourt, Paula; Liu, Hsing-Yin; Parker, Josie E.; Gallo-Ebert, Christina; Donigan, Melissa; Bata, Adam; Giordano, Caroline; Kelly, Steven L.; Nickels, Joseph T.

    2016-01-01

    Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to...

  8. Virulence and antifungal therapy of murine disseminated infection by Rhodotorula mucilaginosa.

    Science.gov (United States)

    Thomson, Pamela; López-Fernández, Loida; Guarro, Josep; Capilla, Javier

    2017-09-01

    Rhodotorula infections have emerged in recent years causing mainly fungemia associated to high mortality. We have evaluated the in vitro activity of nine antifungal drugs against four clinical strains of Rhodotorula mucilaginosa, being amphotericin B, voriconazole and posaconazole the most active compounds. The experimental virulence of this fungus and the efficacy of the three mentioned drugs were evaluated in disseminated infections in neutropenic mice. Infection resulted in a high fungal load in all the organs studied without evident particular tropism. All treated animals showed reduced burden respect to the control in a strain dependent manner being voriconazole slightly superior to posaconazole and amphotericin B. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Isolate-dependent growth, virulence, and cell wall composition in the human pathogen Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    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.

  10. Experimental evolution to increase the efficacy of the entomopathogenic fungus Beauveria bassiana against malaria mosquitoes: Effects on mycelial growth and virulence.

    Science.gov (United States)

    Valero-Jiménez, Claudio A; van Kan, Jan A L; Koenraadt, Constantianus J M; Zwaan, Bas J; Schoustra, Sijmen E

    2017-06-01

    Entomopathogenic fungi such as Beauveria bassiana are currently considered as a potential control agent for malaria mosquitoes. The success of such strategies depends among others on the efficacy of the fungus to kill its hosts. As B. bassiana can use various resources for growth and reproduction, increasing the dependency on mosquitoes as a nutritional source may be instrumental for reaching this goal. Passage of entomopathogenic fungi through an insect host has been shown to increase its virulence. We evaluated the virulence, fungal outgrowth, mycelial growth rate, and sporulation rate of two B. bassiana isolates (Bb1520 and Bb8028) that underwent 10 consecutive selection cycles through malaria mosquitoes ( Anopheles coluzzii ) using an experimental evolution approach. This cycling resulted in an altered capacity of evolved B. Bassiana lineages to grow on different substrates while maintaining the ability to kill insects. Notably, however, there were no significant changes in virulence or speed of outgrowth when comparing the evolved lineages against their unevolved ancestors. These results suggest that fungal growth and sporulation evolved through successive and exclusive use of an insect host as a nutritional resource. We discuss the results in light of biocontrol and provide suggestions to increase fungal virulence.

  11. The Fungal Defensin Family Enlarged

    Directory of Open Access Journals (Sweden)

    Jiajia Wu

    2014-08-01

    Full Text Available Fungi are an emerging source of peptide antibiotics. With the availability of a large number of model fungal genome sequences, we can expect that more and more fungal defensin-like peptides (fDLPs will be discovered by sequence similarity search. Here, we report a total of 69 new fDLPs encoded by 63 genes, in which a group of fDLPs derived from dermatophytes are defined as a new family (fDEF8 according to sequence and phylogenetic analyses. In the oleaginous fungus Mortierella alpine, fDLPs have undergone extensive gene expansion. Our work further enlarges the fungal defensin family and will help characterize new peptide antibiotics with therapeutic potential.

  12. Fungal contamination in hospital environments.

    Science.gov (United States)

    Perdelli, F; Cristina, M L; Sartini, M; Spagnolo, A M; Dallera, M; Ottria, G; Lombardi, R; Grimaldi, M; Orlando, P

    2006-01-01

    To assess the degree of fungal contamination in hospital environments and to evaluate the ability of air conditioning systems to reduce such contamination. We monitored airborne microbial concentrations in various environments in 10 hospitals equipped with air conditioning. Sampling was performed with a portable Surface Air System impactor with replicate organism detection and counting plates containing a fungus-selective medium. The total fungal concentration was determined 72-120 hours after sampling. The genera most involved in infection were identified by macroscopic and microscopic observation. The mean concentration of airborne fungi in the set of environments examined was 19 +/- 19 colony-forming units (cfu) per cubic meter. Analysis of the fungal concentration in the different types of environments revealed different levels of contamination: the lowest mean values (12 +/- 14 cfu/m(3)) were recorded in operating theaters, and the highest (45 +/- 37 cfu/m(3)) were recorded in kitchens. Analyses revealed statistically significant differences between median values for the various environments. The fungal genus most commonly encountered was Penicillium, which, in kitchens, displayed the highest mean airborne concentration (8 +/- 2.4 cfu/m(3)). The percentage (35%) of Aspergillus documented in the wards was higher than that in any of the other environments monitored. The fungal concentrations recorded in the present study are comparable to those recorded in other studies conducted in hospital environments and are considerably lower than those seen in other indoor environments that are not air conditioned. These findings demonstrate the effectiveness of air-handling systems in reducing fungal contamination.

  13. Transcriptional control of drug resistance, virulence and immune system evasion in pathogenic fungi: a cross-species comparison.

    Directory of Open Access Journals (Sweden)

    Pedro Pais

    2016-10-01

    Full Text Available Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis. Current knowledge on the activity of the transcription factors characterized in each of these pathogenic fungal species will be addressed. Particular focus is given to their mechanisms of activation, regulatory targets and phenotypic outcome. The review further provides an evaluation on the conservation of transcriptional circuits among different fungal pathogens, highlighting the pathways that translate common or divergent traits among these species in what concerns their drug resistance, virulence and host immune evasion features. It becomes evident that the regulation of transcriptional networks is complex and presents significant variations among different fungal pathogens. Only the oxidative stress regulators Yap1 and Skn7 are conserved among all studied species; while some transcription factors, involved in nutrient homeostasis, pH adaptation, drug resistance and morphological switching are present in several, though not all species. Interestingly, in some cases not very homologous transcription factors display orthologous functions, whereas some homologous proteins have diverged in terms of their function in different species. A few cases of species specific transcription factors are also observed.

  14. Transcriptional Control of Drug Resistance, Virulence and Immune System Evasion in Pathogenic Fungi: A Cross-Species Comparison.

    Science.gov (United States)

    Pais, Pedro; Costa, Catarina; Cavalheiro, Mafalda; Romão, Daniela; Teixeira, Miguel C

    2016-01-01

    Transcription factors are key players in the control of the activation or repression of gene expression programs in response to environmental stimuli. The study of regulatory networks taking place in fungal pathogens is a promising research topic that can help in the fight against these pathogens by targeting specific fungal pathways as a whole, instead of targeting more specific effectors of virulence or drug resistance. This review is focused on the analysis of regulatory networks playing a central role in the referred mechanisms in the human fungal pathogens Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Candida glabrata, Candida parapsilosis , and Candida tropicalis . Current knowledge on the activity of the transcription factors characterized in each of these pathogenic fungal species will be addressed. Particular focus is given to their mechanisms of activation, regulatory targets and phenotypic outcome. The review further provides an evaluation on the conservation of transcriptional circuits among different fungal pathogens, highlighting the pathways that translate common or divergent traits among these species in what concerns their drug resistance, virulence and host immune evasion features. It becomes evident that the regulation of transcriptional networks is complex and presents significant variations among different fungal pathogens. Only the oxidative stress regulators Yap1 and Skn7 are conserved among all studied species; while some transcription factors, involved in nutrient homeostasis, pH adaptation, drug resistance and morphological switching are present in several, though not all species. Interestingly, in some cases not very homologous transcription factors display orthologous functions, whereas some homologous proteins have diverged in terms of their function in different species. A few cases of species specific transcription factors are also observed.

  15. Septins from the phytopathogenic fungus Ustilago maydis are required for proper morphogenesis but dispensable for virulence.

    Directory of Open Access Journals (Sweden)

    Isabel Alvarez-Tabarés

    Full Text Available BACKGROUND: Septins are a highly conserved family of GTP-binding proteins involved in multiple cellular functions, including cell division and morphogenesis. Studies of septins in fungal cells underpin a clear correlation between septin-based structures and fungal morphology, providing clues to understand the molecular frame behind the varied morphologies found in fungal world. METHODOLOGY/PRINCIPAL FINDINGS: Ustilago maydis genome has the ability to encode four septins. Here, using loss-of-function as well as GFP-tagged alleles of these septin genes, we investigated the roles of septins in the morphogenesis of this basidiomycete fungus. We described that septins in U. maydis could assemble into at least three different structures coexisting in the same cell: bud neck collars, band-like structures at the growing tip, and long septin fibers that run from pole to pole near the cell cortex. We also found that in the absence of septins, U. maydis cells lost their elongated shape, became wider at the central region and ended up losing their polarity, pointing to an important role of septins in the morphogenesis of this fungus. These morphological defects were alleviated in the presence of an osmotic stabilizer suggesting that absence of septins affected the proper formation of the cell wall, which was coherent with a higher sensitivity of septin defective cells to drugs that affect cell wall construction as well as exocytosis. As U. maydis is a phytopathogen, we analyzed the role of septins in virulence and found that in spite of the described morphological defects, septin mutants were virulent in corn plants. CONCLUSIONS/SIGNIFICANCE: Our results indicated a major role of septins in morphogenesis in U. maydis. However, in contrast to studies in other fungal pathogens, in which septins were reported to be necessary during the infection process, we found a minor role of septins during corn infection by U. maydis.

  16. Cuticle-degrading proteases and toxins as virulence markers of Beauveria bassiana (Balsamo) Vuillemin.

    Science.gov (United States)

    Cito, Annarita; Barzanti, Gian Paolo; Strangi, Agostino; Francardi, Valeria; Zanfini, Assunta; Dreassi, Elena

    2016-09-01

    Beauveria bassiana is one of the most known entomopathogenic fungal species and its entomopathogenic mechanism involves several bioactive metabolites, mainly cuticle-degrading enzymes and toxic molecules, which are predicted to play a key role as virulence factors. In this study six Beauveria bassiana strains (B 13/I03, B 13/I11, B 13/I49, B 13/I57, B 13/I63, and B 13/I64) were assayed against Tenebrio molitor larvae. Enzymatic activity of total proteases and specifically Pr 1 and Pr 2, as well as the production of toxic compounds were investigated in each fungal strain. Toxins were detected both in vitro-in medium filtrates and mycelia-and in vivo-in Tenebrio molitor larvae infected by the fungal strains tested. B 13/I11 and B 13/I63 strains showed the most significant entomopathogenic activity against Tenebrio molitor larvae (cumulative mortality rate 100 and 97%, respectively; average survival time 5.85 and 6.74 days, respectively). A widely variable and fungal strain-dependent enzymatic activity of total proteases, Pr 1 and Pr 2 was found. Beauvericin, beauvericin A and bassianolide resulted the most prevalent toxins detected in the substrates analyzed. It has been found that an increase of beauvericin content in vivo resulted significantly correlated to a decrease of Tenebrio molitor larvae average survival time in entomopathogenic bioassay (inverse correlation). The involvement of beauvericin in B. bassiana entomopathogenic process is confirmed; in vitro analysis of cuticle degrading proteases activity and toxins production in relation to the methods adopted resulted insufficient for a rapid screening to determine the virulence of B. bassiana strains against Tenebrio molitor larvae. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

    Directory of Open Access Journals (Sweden)

    Sara eAmorim-Vaz

    2015-05-01

    Full Text Available The aim of the present study was to identify C. albicans transcription factors (TF involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens quantified in kidneys. Mutants of unannotated genes which generated a kidney fungal burden significantly different from that of wild-type were selected and individually examined in G. mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25 % of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects, a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching fungal burden phenotypes were observed in 50 % of the cases, highlighting the bias due to host effects. In contrast, 33.4 % concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the pool effect. After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adaptation.

  18. Anaerobiosis induced virulence of Salmonella typhi

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Singh, R D; Sharma, P C

    2002-01-01

    , we examined the effect of anaerobiosis on the virulence of Salmonella Typhi, a Gram negative bacteria which invades through the gut mucosa and is responsible for typhoid fever. METHODS: Salmonella Typhi (ty2) was cultured in aerobic and anaerobic conditions to compare its virulence by rabbit ileal...

  19. Evolution of viral virulence: empirical studies

    Science.gov (United States)

    Kurath, Gael; Wargo, Andrew R.

    2016-01-01

    The concept of virulence as a pathogen trait that can evolve in response to selection has led to a large body of virulence evolution theory developed in the 1980-1990s. Various aspects of this theory predict increased or decreased virulence in response to a complex array of selection pressures including mode of transmission, changes in host, mixed infection, vector-borne transmission, environmental changes, host vaccination, host resistance, and co-evolution of virus and host. A fundamental concept is prediction of trade-offs between the costs and benefits associated with higher virulence, leading to selection of optimal virulence levels. Through a combination of observational and experimental studies, including experimental evolution of viruses during serial passage, many of these predictions have now been explored in systems ranging from bacteriophage to viruses of plants, invertebrates, and vertebrate hosts. This chapter summarizes empirical studies of viral virulence evolution in numerous diverse systems, including the classic models myxomavirus in rabbits, Marek's disease virus in chickens, and HIV in humans. Collectively these studies support some aspects of virulence evolution theory, suggest modifications for other aspects, and show that predictions may apply in some virus:host interactions but not in others. Finally, we consider how virulence evolution theory applies to disease management in the field.

  20. Virulence, serotype and phylogenetic groups of diarrhoeagenic ...

    African Journals Online (AJOL)

    Dr DADIE Thomas

    2014-02-17

    Feb 17, 2014 ... The virulence, serotype and phylogenetic traits of diarrhoeagenic Escherichia coli were detected in 502 strains isolated during digestive infections. Molecular detection of the target virulence genes, rfb gene of operon O and phylogenetic grouping genes Chua, yjaA and TSPE4.C2 was performed.

  1. Patterns of variation at Ustilago maydis virulence clusters 2A and 19A largely reflect the demographic history of its populations.

    Directory of Open Access Journals (Sweden)

    Ronny Kellner

    Full Text Available The maintenance of an intimate interaction between plant-biotrophic fungi and their hosts over evolutionary times involves strong selection and adaptative evolution of virulence-related genes. The highly specialised maize pathogen Ustilago maydis is assigned with a high evolutionary capability to overcome host resistances due to its high rates of sexual recombination, large population sizes and long distance dispersal. Unlike most studied fungus-plant interactions, the U. maydis - Zea mays pathosystem lacks a typical gene-for-gene interaction. It exerts a large set of secreted fungal virulence factors that are mostly organised in gene clusters. Their contribution to virulence has been experimentally demonstrated but their genetic diversity within U. maydis remains poorly understood. Here, we report on the intraspecific diversity of 34 potential virulence factor genes of U. maydis. We analysed their sequence polymorphisms in 17 isolates of U. maydis from Europe, North and Latin America. We focused on gene cluster 2A, associated with virulence attenuation, cluster 19A that is crucial for virulence, and the cluster-independent effector gene pep1. Although higher compared to four house-keeping genes, the overall levels of intraspecific genetic variation of virulence clusters 2A and 19A, and pep1 are remarkably low and commensurate to the levels of 14 studied non-virulence genes. In addition, each gene is present in all studied isolates and synteny in cluster 2A is conserved. Furthermore, 7 out of 34 virulence genes contain either no polymorphisms or only synonymous substitutions among all isolates. However, genetic variation of clusters 2A and 19A each resolve the large scale population structure of U. maydis indicating subpopulations with decreased gene flow. Hence, the genetic diversity of these virulence-related genes largely reflect the demographic history of U. maydis populations.

  2. Fungal Cytochrome P450s and the P450 Complement (CYPome of Fusarium graminearum

    Directory of Open Access Journals (Sweden)

    Jiyoung Shin

    2018-03-01

    Full Text Available Cytochrome P450s (CYPs, heme-containing monooxygenases, play important roles in a wide variety of metabolic processes important for development as well as biotic/trophic interactions in most living organisms. Functions of some CYP enzymes are similar across organisms, but some are organism-specific; they are involved in the biosynthesis of structural components, signaling networks, secondary metabolisms, and xenobiotic/drug detoxification. Fungi possess more diverse CYP families than plants, animals, or bacteria. Various fungal CYPs are involved in not only ergosterol synthesis and virulence but also in the production of a wide array of secondary metabolites, which exert toxic effects on humans and other animals. Although few studies have investigated the functions of fungal CYPs, a recent systematic functional analysis of CYP genes in the plant pathogen Fusarium graminearum identified several novel CYPs specifically involved in virulence, asexual and sexual development, and degradation of xenobiotics. This review provides fundamental information on fungal CYPs and a new platform for further metabolomic and biochemical studies of CYPs in toxigenic fungi.

  3. Production Of Some Virulence Factors Under Different Growth ...

    African Journals Online (AJOL)

    Production Of Some Virulence Factors Under Different Growth Conditions And Antibiotic Susceptibility Pattern Of ... Animal Research International ... Keywords: Virulence, Haemolytic activity, Susceptibility, Antibiotics, Aeromonas hydrophila

  4. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  5. Pyrokinin β-neuropeptide affects necrophoretic behavior in fire ants (S. invicta), and expression of β-NP in a mycoinsecticide increases its virulence.

    Science.gov (United States)

    Fan, Yanhua; Pereira, Roberto M; Kilic, Engin; Casella, George; Keyhani, Nemat O

    2012-01-01

    Fire ants are one of the world's most damaging invasive pests, with few means for their effective control. Although ecologically friendly alternatives to chemical pesticides such as the insecticidal fungus Beauveria bassiana have been suggested for the control of fire ant populations, their use has been limited due to the low virulence of the fungus and the length of time it takes to kill its target. We present a means of increasing the virulence of the fungal agent by expressing a fire ant neuropeptide. Expression of the fire ant (Solenopsis invicta) pyrokinin β-neuropeptide (β-NP) by B. bassiana increased fungal virulence six-fold towards fire ants, decreased the LT(50), but did not affect virulence towards the lepidopteran, Galleria mellonella. Intriguingly, ants killed by the β-NP expressing fungus were disrupted in the removal of dead colony members, i.e. necrophoretic behavior. Furthermore, synthetic C-terminal amidated β-NP but not the non-amidated peptide had a dramatic effect on necrophoretic behavior. These data link chemical sensing of a specific peptide to a complex social behavior. Our results also confirm a new approach to insect control in which expression of host molecules in an insect pathogen can by exploited for target specific augmentation of virulence. The minimization of the development of potential insect resistance by our approach is discussed.

  6. Fungal Endophytes: Beyond Herbivore Management

    Directory of Open Access Journals (Sweden)

    Bamisope S. Bamisile

    2018-03-01

    Full Text Available The incorporation of entomopathogenic fungi as biocontrol agents into Integrated Pest Management (IPM programs without doubt, has been highly effective. The ability of these fungal pathogens such as Beauveria bassiana and Metarhizium anisopliae to exist as endophytes in plants and protect their colonized host plants against the primary herbivore pests has widely been reported. Aside this sole role of pest management that has been traditionally ascribed to fungal endophytes, recent findings provided evidence of other possible functions as plant yield promoter, soil nutrient distributor, abiotic stress and drought tolerance enhancer in plants. However, reports on these additional important effects of fungal endophytes on the colonized plants remain scanty. In this review, we discussed the various beneficial effects of endophytic fungi on the host plants and their primary herbivore pests; as well as some negative effects that are relatively unknown. We also highlighted the prospects of our findings in further increasing the acceptance of fungal endophytes as an integral part of pest management programs for optimized crop production.

  7. DEMONSTRATION BULLETIN: FUNGAL TREATMENT BULLETIN

    Science.gov (United States)

    Fungal treatment technology uses white rot fungi (lignin degrading fungi) to treat organic contaminated soils in situ. Organic materials inoculated with the fungi are mechanically mixed into the contaminated soil. Using enzymes normally produced for wood degradation as well as ot...

  8. [Fungal infections of the gastrointestinal tract].

    Science.gov (United States)

    Maragkoudakis, Emmanouil; Realdi, Giuseppe; Dore, Maria Pina

    2005-06-01

    In immunocompetent subjects fungal infections of the gastrointestinal tract are uncommon. Candida esophagitis remains the single most common fungal infection in immunocompromised hosts or in H. pylori- infected patients who receive antibiotic therapy. Enteric fungal infections are uncommon even in HIV-infected patients. Antifungal agents such as amphotericin B, ketoconazole, fluconazole, and the various formulations of itraconazole are effective for most cases.

  9. Daphnia can protect diatoms from fungal parasitism

    NARCIS (Netherlands)

    Kagami, M.; Van Donk, E.; De Bruin, A.; Rijkeboer, M.; Ibelings, B.W.

    2004-01-01

    Many phytoplankton species are susceptible to chytrid fungal parasitism. Much attention has been paid to abiotic factors that determine whether fungal infections become epidemic. It is still unknown, however, how biotic factors, such as interactions with zooplankton, affect the fungal infection

  10. Subseafloor basalts as fungal habitats

    Directory of Open Access Journals (Sweden)

    M. Ivarsson

    2012-09-01

    Full Text Available The oceanic crust is believed to host the largest potential habitat for microbial life on Earth, yet, still we lack substantial information about the abundance, diversity, and consequence of its biosphere. The last two decades have involved major research accomplishments within this field and a change in view of the ocean crust and its potential to harbour life. Here fossilised fungal colonies in subseafloor basalts are reported from three different seamounts in the Pacific Ocean. The fungal colonies consist of various characteristic structures interpreted as fungal hyphae, fruit bodies and spores. The fungal hyphae are well preserved with morphological characteristics such as hyphal walls, septa, thallic conidiogenesis, and hyphal tips with hyphal vesicles within. The fruit bodies consist of large (∼50–200 µm in diameter body-like structures with a defined outer membrane and an interior filled with calcite. The fruit bodies have at some stage been emptied of their contents of spores and filled by carbonate-forming fluids. A few fruit bodies not filled by calcite and with spores still within support this interpretation. Spore-like structures (ranging from a few µm to ∼20 µm in diameter are also observed outside of the fruit bodies and in some cases concentrated to openings in the membrane of the fruit bodies. The hyphae, fruit bodies and spores are all closely associated with a crust lining the vein walls that probably represent a mineralized biofilm. The results support a fungal presence in deep subseafloor basalts and indicate that such habitats were vital between ∼81 and 48 Ma.

  11. Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2.

    Science.gov (United States)

    Forslund, Carina; Aspenberg, Per

    2003-01-01

    Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Controlled laboratory study. The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 micro g) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

  12. Global Insight into Lysine Acetylation Events and Their Links to Biological Aspects in Beauveria bassiana, a Fungal Insect Pathogen

    Science.gov (United States)

    Wang, Zhi-Kang; Cai, Qing; Liu, Jin; Ying, Sheng-Hua; Feng, Ming-Guang

    2017-01-01

    Lysine acetylation (Kac) events in filamentous fungi are poorly explored. Here we show a lysine acetylome generated by LC-MS/MS analysis of immunoaffinity-based Kac peptides from normal hyphal cells of Beauveria bassiana, a fungal entomopathogen. The acetylome comprised 283 Kac proteins and 464 Kac sites. These proteins were enriched to eight molecular functions, 20 cellular components, 27 biological processes, 20 KEGG pathways and 12 subcellular localizations. All Kac sites were characterized as six Kac motifs, including a novel motif (KacW) for 26 Kac sites of 17 unknown proteins. Many Kac sites were predicted to be multifunctional, largely expanding the fungal Kac events. Biological importance of identified Kac sites was confirmed through functional analysis of Kac sites on Pmt1 and Pmt4, two O-mannosyltransferases. Singular site mutations (K88R and K482R) of Pmt1 resulted in impaired conidiation, attenuated virulence and decreased tolerance to oxidation and cell wall perturbation. These defects were close to or more severe than those caused by the deletion of pmt1. The Pmt4 K360R mutation facilitated colony growth under normal and stressful conditions and enhanced the fungal virulence. Our findings provide the first insight into the Kac events of B. bassiana and their links to the fungal potential against insect pests. PMID:28295016

  13. DIAGNOSIS & MANAGEMENT OF ALLERGIC FUNGAL SINUSITIS

    Directory of Open Access Journals (Sweden)

    Syam Manohar Gadhamsetty

    2016-08-01

    Full Text Available BACKGROUND Chronic sinusitis is one of the common diagnosis in ENT practice. Allergic fungal sinusitis is a clinical entity with characteristic clinical, radiographic and histopathological findings. Allergic fungal sinusitis and eosinophilic mucin rhinosinusitis can easily be misdiagnosed. AIM OF STUDY A prospective clinical study of allergic Fungal Rhinosinusitis to use diagnostic criteria to confirm the disease with Radiological, Pathological & Microbiological investigations and their management. MATERIALS & METHODS A prospective study of allergic Fungal Rhinosinusitis in 2 years from November 2011 to October 2013. Among the patients who attended the ENT OPD during this period, 21 patients with symptoms and signs suggestive of Allergic Fungal Rhinosinusitis are selected.

  14. Maxillary anterior ridge augmentation with recombinant human bone morphogenetic protein 2.

    Science.gov (United States)

    Edmunds, Ryan K; Mealey, Brian L; Mills, Michael P; Thoma, Daniel S; Schoolfield, John; Cochran, David L; Mellonig, Jim

    2014-01-01

    No human studies exist on the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an absorbable collagen sponge (ACS) as a sole graft material for lateral ridge augmentation in large ridge defect sites. This series evaluates the treatment outcome of maxillary anterior lateral ridge augmentation with rhBMP-2/ACS. Twenty patients were treated with rhBMP-2/ACS and fixation screws for space maintenance. Cone beam volumetric tomography measurements were used to determine gain in ridge width, and a bone core biopsy was obtained. The mean horizontal ridge gain was 1.2 mm across sites, and every site gained width.

  15. Productive and morphogenetic responses of buffel grass at different air temperatures and CO2 concentrations

    OpenAIRE

    Santos, Roberta Machado; Voltolini, Tadeu Vinhas; Angelotti, Francislene; Aidar, Saulo de Tarso; Chaves, Agnaldo Rodrigues de Melo

    2014-01-01

    The objective of the present trial was to evaluate the productive and morphogenetic characteristics of buffel grass subjected to different air temperatures and CO2 concentrations. Three cultivars of buffel grass (Biloela, Aridus and West Australian) were compared. Cultivars were grown in growth chambers at three temperatures (day/night): 26/20, 29/23, and 32/26 °C, combined with two concentrations of CO2: 370 and 550 µmol mol-1. The experimental design was completely randomized, in a 3 × 3 × ...

  16. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

    DEFF Research Database (Denmark)

    Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi

    2014-01-01

    : Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2...... signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox...

  17. Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulation.

    Science.gov (United States)

    Pragman, Alexa A; Schlievert, Patrick M

    2004-10-01

    Staphylococcus aureus is a pathogenic microorganism that is responsible for a wide variety of clinical infections. These infections can be relatively mild, but serious, life-threatening infections may result from the expression of staphylococcal virulence factors that are coordinated by virulence regulators. Much work has been done to characterize the actions of staphylococcal virulence regulators in broth culture. Recently, several laboratories showed that transcriptional analyses of virulence regulators in in vivo animal models or in human infection did not correlate with transcriptional analyses accomplished in vitro. In describing the differences between in vitro and in vivo transcription of staphylococcal virulence regulators, we hope to encourage investigators to study virulence regulators using infection models whenever possible.

  18. Identification and functional characterization of proteases and protease inhibitors involved in virulence of fungal tomato pathogens

    NARCIS (Netherlands)

    Karimi Jashni, M.

    2015-01-01

    Pathogens cause disease on both animal and plant hosts. For successful infection and establishment of disease, pathogens need proper weaponry to protect themselves against host defenses and to promote host colonization to facilitate uptake of nutrients for growth and reproduction. Indeed, plant

  19. Polygalacturonase gene pgxB in Aspergillus niger is a virulence factor in apple fruit.

    Science.gov (United States)

    Liu, Cheng-Qian; Hu, Kang-Di; Li, Ting-Ting; Yang, Ying; Yang, Feng; Li, Yan-Hong; Liu, He-Ping; Chen, Xiao-Yan; Zhang, Hua

    2017-01-01

    Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type. Pectin medium induced significant higher expression of all pectinase genes in both wild type and ΔpgxB in comparison to potato dextrose agar medium. However, the ΔpgxB mutant was less virulent on apple fruits as the necrosis diameter caused by ΔpgxB mutant was significantly smaller than that of wild type. Results of quantitive-PCR showed that, in the process of infection in apple fruit, gene expressions of polygalacturonase genes pgaI, pgaII, pgaA, pgaC, pgaD and pgaE were enhanced in ΔpgxB mutant in comparison to wild type. These results prove that, despite the increased gene expression of other polygalacturonase genes in ΔpgxB mutant, the lack of pgxB gene significantly reduced the virulence of A. niger on apple fruit, suggesting that pgxB plays an important role in the infection process on the apple fruit.

  20. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

    Science.gov (United States)

    McCourt, Paula; Liu, Hsing-Yin; Parker, Josie E.; Gallo-Ebert, Christina; Donigan, Melissa; Bata, Adam; Giordano, Caroline; Kelly, Steven L.; Nickels, Joseph T.

    2016-01-01

    Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution. PMID:27587298

  1. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

    Directory of Open Access Journals (Sweden)

    Paula McCourt

    2016-11-01

    Full Text Available Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution.

  2. Fungal Endocarditis Due to Aspergillus oryzae: The First Case Reported in the Literature.

    Science.gov (United States)

    Mazza, Andrea; Luciani, Nicola; Luciani, Marco; Cammertoni, Federico; Giaquinto, Alessia; Pavone, Natalia; Bruno, Piergiorgio; Massetti, Massimo

    2017-03-01

    Infective endocarditis (IE) is a severe disease with high mortality and morbidity. Prosthetic valve endocarditis is a life-threatening complication which can occur in less than 10% of patients with valve prosthesis. A fungal etiology of IE is rare and accounts for only 2-4% of all case of endocarditis, but is associated with a higher mortality and morbidity. Herein is reported the first case of fungal endocarditis of aortic valve prosthesis due to Aspergillus oryzae in a 67-year-old caucasian man who nine years previously underwent mitral and aortic valve replacement with mechanical prostheses, and tricuspid annuloplasty for acute IE due to Enterococcus spp. Seven months previously, the patient also underwent a redo cardiac procedure to replace a mitral valve prosthesis with a new mechanical device due to a leakage. Aspergillus oryzae showed impressive growth with strong and unexpected virulence in both local and systemic settings.

  3. Amino Acid Permeases and Virulence in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Kevin Felipe Cruz Martho

    Full Text Available Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis, where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work

  4. Exploring potential virulence regulators in Paracoccidioides brasiliensis isolates of varying virulence through quantitative proteomics.

    Science.gov (United States)

    Castilho, Daniele G; Chaves, Alison F A; Xander, Patricia; Zelanis, André; Kitano, Eduardo S; Serrano, Solange M T; Tashima, Alexandre K; Batista, Wagner L

    2014-10-03

    Few virulence factors have been identified for Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. In this study, we quantitatively evaluated the protein composition of P. brasiliensis in the yeast phase using minimal and rich media to obtain a better understanding of its virulence and to gain new insights into pathogen adaptation strategies. This analysis was performed on two isolates of the Pb18 strain showing distinct infection profiles in B10.A mice. Using liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis, we identified and quantified 316 proteins in minimal medium, 29 of which were overexpressed in virulent Pb18. In rich medium, 29 out of 295 proteins were overexpressed in the virulent fungus. Three proteins were found to be up-regulated in both media, suggesting the potential roles of these proteins in virulence regulation in P. brasiliensis. Moreover, genes up-regulated in virulent Pb18 showed an increase in its expression after the recovery of virulence of attenuated Pb18. Proteins up-regulated in both isolates were grouped according to their functional categories. Virulent Pb18 undergoes metabolic reorganization and increased expression of proteins involved in fermentative respiration. This approach allowed us to identify potential virulence regulators and provided a foundation for achieving a molecular understanding of how Paracoccidioides modulates the host-pathogen interaction to its advantage.

  5. [Virulence and its relationship to antibiotic resistance].

    Science.gov (United States)

    Joly-Guillou, M L

    1998-12-01

    PATHOGENIC ISLANDS: Certain DNA blocks inserted into the chromosome of most Gram negative bacteria originated in pathogens found in plants. VIRULENCE-ANTIBIOTIC INTERACTIONS: During the invasive phase, the bacterial cell covers itself with adhesins which facilitate its adherence to tissues. The bacterial cell produces a fibronectin which protects its defense systems. Antibiotics favor bacterial resistance by increasing the expression of surface adhesins and fibronectin production. PENICILLIN RESISTANT PNEUMOCOCCI: Experimental models have demonstrated that mortality in mice and host resistance to pneumococcal infection are related to the type of capsule and not to antibiotic resistance. QUORUM SENSING: The bacterial inoculum regulates the production of virulence factors in vivo via quorum sensing. This regulation can play an important role in Pseudomonas aeruginosa infections. ACINETOBACTER BAUMANNI VIRULENCE: Long poorly understood, factors favoring A. baumanni virulence appear to result from bacterial production of IROMPs in the extracellular growth medium in response to iron depletion during the exponential growth phase.

  6. Subseafloor basalts as fungal habitats

    Science.gov (United States)

    Ivarsson, M.; Bengtson, S.

    2013-12-01

    The oceanic crust makes up the largest potential habitat for life on Earth, yet next to nothing is known about the abundance, diversity and ecology of its biosphere. Our understanding of the deep biosphere of subseafloor crust is, with a few exceptions, based on a fossil record. Surprisingly, a majority of the fossilized microorganisms have been interpreted or recently re-interpreted as remnants of fungi rather than prokaryotes. Even though this might be due to a bias in fossilization the presence of fungi in these settings can not be neglected. We have examined fossilized microorganisms in drilled basalt samples collected at the Emperor Seamounts in the Pacific Ocean. Synchrotron-radiation X-ray tomography microscopy (SRXTM) studies has revealed a complex morphology and internal structure that corresponds to characteristic fungal morphology. Chitin was detected in the fossilized hyphae, which is another strong argument in favour of a fungal interpretation. Chitin is absent in prokaryotes but a substantial constituent in fungal cell walls. The fungal colonies consist of both hyphae and yeast-like growth states as well as resting structures and possible fruit bodies, thus, the fungi exist in vital colonies in subseafloor basalts. The fungi have also been involved in extensive weathering of secondary mineralisations. In terrestrial environments fungi are known as an important geobiological agent that promotes mineral weathering and decomposition of organic matter, and they occur in vital symbiosis with other microorganisms. It is probable to assume that fungi would play a similar role in subseafloor basalts and have great impact on the ecology and on biogeochemical cycles in such environments.

  7. Systemic fungal infections in neonates

    Directory of Open Access Journals (Sweden)

    Rao S

    2005-01-01

    Full Text Available Advances in neonatal management have led to considerable improvement in newborn survival. However, early (72hours onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp -LRC-1 has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.

  8. Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

    Science.gov (United States)

    Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  9. When green and red mycology meet: Impressions from an interdisciplinary forum on virulence mechanisms of phyto- and human-pathogenic fungi.

    Science.gov (United States)

    Yu, Yidong; Hube, Bernhard; Kämper, Jörg; Meyer, Vera; Krappmann, Sven

    2017-10-03

    Fungal infections pose a constant threat to plants and humans, but detailed knowledge about pathogenesis, immunity, or virulence is rather scarce. Due to the fact that a certain overlap in the armoury of infection exists between plant- and human-pathogenic fungi, an interdisciplinary forum was held in October 2016 at the Institute for Clinical Microbiology, Immunology and Hygiene in Erlangen under the organisational umbrella from two special interest groups of German microbial societies. Scientific exchange and intense discussion of this timely topic was fostered by bringing together renowned experts in their respective fields to present their thoughts and recent findings in the course of a plenary lecture and six themed sessions, accompanied by oral and poster contributions of young researchers. By targeting the topic of fungal virulence mechanisms from various angles and in the context of plant and human hosts, some common grounds and exciting perspectives could be deduced during this vibrant scientific event.

  10. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  11. Fungal genome resources at NCBI

    Science.gov (United States)

    Robbertse, B.; Tatusova, T.

    2011-01-01

    The National Center for Biotechnology Information (NCBI) is well known for the nucleotide sequence archive, GenBank and sequence analysis tool BLAST. However, NCBI integrates many types of biomolecular data from variety of sources and makes it available to the scientific community as interactive web resources as well as organized releases of bulk data. These tools are available to explore and compare fungal genomes. Searching all databases with Fungi [organism] at http://www.ncbi.nlm.nih.gov/ is the quickest way to find resources of interest with fungal entries. Some tools though are resources specific and can be indirectly accessed from a particular database in the Entrez system. These include graphical viewers and comparative analysis tools such as TaxPlot, TaxMap and UniGene DDD (found via UniGene Homepage). Gene and BioProject pages also serve as portals to external data such as community annotation websites, BioGrid and UniProt. There are many different ways of accessing genomic data at NCBI. Depending on the focus and goal of research projects or the level of interest, a user would select a particular route for accessing genomic databases and resources. This review article describes methods of accessing fungal genome data and provides examples that illustrate the use of analysis tools. PMID:22737589

  12. Enhanced release of bone morphogenetic proteins from demineralized bone matrix by gamma irradiation

    International Nuclear Information System (INIS)

    Sung, Nak-Yun; Choi, Jong-il

    2015-01-01

    Gamma irradiation is a useful method for sterilizing demineralized bone matrix (DBM), but its effect on the osteoinductivity of DBM is still controversial. In this study, the osteoinductive activity of gamma-irradiated DBM was examined using a mouse myoblastic cell line (C2C12). DBM was extracted from adult bovine bone and was irradiated at a dose of 25 kGy using a 60 cobalt gamma-irradiator. Cell proliferation with DBM was not affected by gamma-irradiation, but alkaline phosphatase and osteocalcin productions were significantly increased in C2C12 cell groups treated with gamma-irradiated DBM. It was reasoned that bone morphogenetic proteins were more efficiently released from gamma-irradiated DBM than from the non-irradiated control. This result suggests the effectiveness of radiation sterilization of bone implants - Highlights: • Demineralized bone matrix (DBM) was gamma-irradiated for sterilization. • Irradiated DBM had higher alkaline phosphatase and osteocalcin production. • It was reasoned the more released bone morphogenetic proteins by irradiation. • This result supports the application of radiation sterilization for bone implants

  13. Bone morphogenetic protein-7 promotes chondrogenesis in human amniotic epithelial cells.

    Science.gov (United States)

    Zhou, Junjie; Yu, Guangrong; Cao, Chengfu; Pang, Jinhui; Chen, Xianqi

    2011-06-01

    Bone morphogenetic proteins (BMPs) play important roles at multiple stages of chondrogenesis. This study was undertaken to investigate the potential role of bone morphogenetic protein-7 (BMP-7) in the differentiation of chondrocytes using tissue engineering techniques. The impact of BMP-7 on human amniotic epithelial cells (hAECs) was tested. The hAECs were treated either with recombinant human BMP-7 cDNA or with transforming growth factor beta 1 (TGF-β1) as a positive control for three weeks in vitro. Cartilaginous differentiation and proliferation were assayed by quantitative RT-PCR, histology, and in situ hybridization. Our results were such that hAECs treated with either BMP-7 or TGF-β1 expressed cartilage markers (aggrecan, Sox9, CEP-68, and type II and X collagens) within three weeks. Compared with a control vector, BMP-7 induced a decrease in type I collagen expression, while the transcription of the cartilage-specific type II collagen remained stable. In induction experiments, BMP-7 transgenic hAECs exhibited the largest amount of matrix synthesis. In conclusion, these data indicate that BMP-7 plays an important role in inducing the production of cartilage by hAECs in vitro. Cartilage differentiation and matrix maturation can be promoted by BMPs in a cartilage engineering paradigm. These properties make BMPs promising tools in the engineering of cartilaginous joint bio-prostheses and as candidate biological agents or genes for cartilage stabilisation.

  14. Virulence Factors of Helicobacter pylori

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    Paul Sinclair

    1991-01-01

    environment with respect to pH. The spiral shape of the cells and their flagellar motility allow them to wind themselves into the mucous layer of the stomach. Some evidence exists for the production of strong proteolytic activity, hence degrading the mucous barrier and increasing permeability for the organism. Cyroroxin excreted by the bacteria may have some effect on the surrounding cells, with the possible lysis and release of bacterial growth factors. There is evidence that a chemotactic response is present due to these growth factors and their higher concentration in the intracellular spaces. The presence of specific and nonspecific adhesion has also been demonstrated, thus allowing the bacterium, once at the epithelial cell surface, to attach and avoid being washed off by movement within the stomach. Although treatment with antimicrobials eradicates the organism and improves symptoms of peptic ulcer patients, there is no indication that the same occurs in nonulcer dyspepsia patients. Further work is essential to describe the virulence mechanisms of H pylori and the possible pathogenic role of the organism.

  15. Molecular epidemiology and virulence assessment of Aspergillus fumigatus isolates from white stork chicks and their environment.

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    Olias, Philipp; Gruber, Achim D; Hafez, Hafez M; Lierz, Michael; Slesiona, Silvia; Brock, Matthias; Jacobsen, Ilse D

    2011-03-24

    Aspergillus fumigatus is a common pathogen in poultry and captive wild birds and an emerging opportunistic fungal pathogen in immunocompromised humans. Although invasive aspergillosis is frequently reported in free-ranging wild birds, the incidence and epidemiology of the disease in a natural setting is unknown. We recently reported endemic outbreaks of invasive aspergillosis at white stork nesting sites close to human habitation in Germany with significant subsequent breeding losses. Therefore, we hypothesized that A. fumigatus strains with higher virulence in birds may have evolved in this environment and performed the first epidemiological analysis of invasive aspergillosis in free-ranging wild birds. Sixty-one clinical and environmental A. fumigatus isolates from six affected nesting sites were genotyped by microsatellite analysis using the STRAf-assay. The isolates showed a remarkable high genomic diversity and, contrary to the initial hypothesis, clinical and environmental isolates did not cluster significantly. Interestingly, storks were infected with two to four different genotypes and in most cases both mating types MAT-1.1 and MAT-1.2 were present within the same specimen. The majority of selected clinical and environmental strains exhibited similar virulence in an in vivo infection model using embryonated chicken eggs. Noteworthy, virulence was not associated with one distinct fungal mating type. These results further support the assumption that the majority of A. fumigatus strains have the potential to cause disease in susceptible hosts. In white storks, immaturity of the immune system during the first three weeks of age may enhance susceptibility to invasive aspergillosis. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo

    Science.gov (United States)

    Falsetta, Megan L.; Klein, Marlise I.; Colonne, Punsiri M.; Scott-Anne, Kathleen; Gregoire, Stacy; Pai, Chia-Hua; Gonzalez-Begne, Mireya; Watson, Gene; Krysan, Damian J.; Bowen, William H.

    2014-01-01

    Streptococcus mutans is often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC). S. mutans may not act alone; Candida albicans cells are frequently detected along with heavy infection by S. mutans in plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viable S. mutans cells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeable S. mutans microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Our in vitro data also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence with C. albicans induces the expression of virulence genes in S. mutans (e.g., gtfB, fabM). We also found that Candida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease. PMID:24566629

  17. A novel high-affinity sucrose transporter is required for virulence of the plant pathogen Ustilago maydis.

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    Ramon Wahl

    2010-02-01

    Full Text Available Plant pathogenic fungi cause massive yield losses and affect both quality and safety of food and feed produced from infected plants. The main objective of plant pathogenic fungi is to get access to the organic carbon sources of their carbon-autotrophic hosts. However, the chemical nature of the carbon source(s and the mode of uptake are largely unknown. Here, we present a novel, plasma membrane-localized sucrose transporter (Srt1 from the corn smut fungus Ustilago maydis and its characterization as a fungal virulence factor. Srt1 has an unusually high substrate affinity, is absolutely sucrose specific, and allows the direct utilization of sucrose at the plant/fungal interface without extracellular hydrolysis and, thus, without the production of extracellular monosaccharides known to elicit plant immune responses. srt1 is expressed exclusively during infection, and its deletion strongly reduces fungal virulence. This emphasizes the central role of this protein both for efficient carbon supply and for avoidance of apoplastic signals potentially recognized by the host.

  18. Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis.

    Science.gov (United States)

    Stirnberg, Alexandra; Djamei, Armin

    2016-12-01

    The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar-specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize-infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. © 2016 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

  19. Significance of hyphae formation in virulence of Candida tropicalis and transcriptomic analysis of hyphal cells.

    Science.gov (United States)

    Jiang, Cen; Li, Zhen; Zhang, Lihua; Tian, Yuan; Dong, Danfeng; Peng, Yibing

    2016-11-01

    Recently, the proportion of Candida tropicalis in clinical isolates has significantly increased. Some C. tropicalis strains colonize the skin or mucosal surfaces as commensals; others trigger invasive infection. To date, the pathogenicity of C. tropicalis has not been thoroughly researched. This study reports several virulence factors, including biofilm and hyphae formation, proteinase, phospholipase, lipase and hemolytic activity, in 52 clinical isolates of C. tropicalis collected from five hospitals in four provinces of China. Some C. tropicalis tended to produce more hyphae than others in the same circumstance. Six C. tropicalis strains with different morphologies were injected into mice via the tail vein, and the survival proportions and fungal burdens of the strains were evaluated. Hyphal production by C. tropicalis was associated with stronger virulence. RNA sequencing revealed that C. tropicalis with more hyphae up-regulated several genes involved in morphological differentiation and oxidative response, including IF2, Atx1, and Sod2. It appears that hyphal formation plays a vital role in the pathogenicity of C. tropicalis, and interacts with the oxidative stress response to strengthen the organism's virulence. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Glycosylphosphatidylinositol-Anchored Proteins in Fusarium graminearum: Inventory, Variability, and Virulence

    Science.gov (United States)

    Rittenour, William R.; Harris, Steven D.

    2013-01-01

    The contribution of cell surface proteins to plant pathogenicity of fungi is not well understood. As such, the objective of this study was to investigate the functions and importance of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in the wheat pathogen F. graminearum. GPI-APs are surface proteins that are attached to either the membrane or cell wall. In order to simultaneously disrupt several GPI-APs, a phosphoethanolamine transferase-encoding gene gpi7 was deleted and the resultant mutant characterized in terms of growth, development, and virulence. The Δgpi7 mutants exhibited slower radial growth rates and aberrantly shaped macroconidia. Furthermore, virulence tests and microscopic analyses indicated that Gpi7 is required for ramification of the fungus throughout the rachis of wheat heads. In parallel, bioinformatics tools were utilized to predict and inventory GPI-APs within the proteome of F. graminearum. Two of the genes identified in this screen (FGSG_01588 and FGSG_08844) displayed isolate-specific length variability as observed for other fungal cell wall adhesion genes. Nevertheless, deletion of these genes failed to reveal obvious defects in growth, development, or virulence. This research demonstrates the global importance of GPI-APs to in planta proliferation in F. graminearum, and also highlights the potential of individual GPI-APs as diagnostic markers. PMID:24312325

  1. Phylogenetic distribution of fungal sterols.

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    John D Weete

    Full Text Available BACKGROUND: Ergosterol has been considered the "fungal sterol" for almost 125 years; however, additional sterol data superimposed on a recent molecular phylogeny of kingdom Fungi reveals a different and more complex situation. METHODOLOGY/PRINCIPAL FINDINGS: The interpretation of sterol distribution data in a modern phylogenetic context indicates that there is a clear trend from cholesterol and other Delta(5 sterols in the earliest diverging fungal species to ergosterol in later diverging fungi. There are, however, deviations from this pattern in certain clades. Sterols of the diverse zoosporic and zygosporic forms exhibit structural diversity with cholesterol and 24-ethyl -Delta(5 sterols in zoosporic taxa, and 24-methyl sterols in zygosporic fungi. For example, each of the three monophyletic lineages of zygosporic fungi has distinctive major sterols, ergosterol in Mucorales, 22-dihydroergosterol in Dimargaritales, Harpellales, and Kickxellales (DHK clade, and 24-methyl cholesterol in Entomophthorales. Other departures from ergosterol as the dominant sterol include: 24-ethyl cholesterol in Glomeromycota, 24-ethyl cholest-7-enol and 24-ethyl-cholesta-7,24(28-dienol in rust fungi, brassicasterol in Taphrinales and hypogeous pezizalean species, and cholesterol in Pneumocystis. CONCLUSIONS/SIGNIFICANCE: Five dominant end products of sterol biosynthesis (cholesterol, ergosterol, 24-methyl cholesterol, 24-ethyl cholesterol, brassicasterol, and intermediates in the formation of 24-ethyl cholesterol, are major sterols in 175 species of Fungi. Although most fungi in the most speciose clades have ergosterol as a major sterol, sterols are more varied than currently understood, and their distribution supports certain clades of Fungi in current fungal phylogenies. In addition to the intellectual importance of understanding evolution of sterol synthesis in fungi, there is practical importance because certain antifungal drugs (e.g., azoles target reactions in

  2. The ventralizing activity of Radar, a maternally expressed bone morphogenetic protein, reveals complex bone morphogenetic protein interactions controlling dorso-ventral patterning in zebrafish.

    Science.gov (United States)

    Goutel, C; Kishimoto, Y; Schulte-Merker, S; Rosa, F

    2000-12-01

    In Xenopus and zebrafish, BMP2, 4 and 7 have been implicated, after the onset of zygotic expression, in inducing and maintaining ventro-lateral cell fate during early development. We provide evidence here that a maternally expressed bone morphogenetic protein (BMP), Radar, may control early ventral specification in zebrafish. We show that Radar ventralizes zebrafish embryos and induces the early expression of bmp2b and bmp4. The analysis of Radar overexpression in both swirl/bmp2b mutants and embryos expressing truncated BMP receptors shows that Radar-induced ventralization is dependent on functional BMP2/4 pathways, and may initially rely on an Alk6-related signaling pathway. Finally, we show that while radar-injected swirl embryos still exhibit a strongly dorsalized phenotype, the overexpression of Radar into swirl/bmp2b mutant embryos restores ventral marker expression, including bmp4 expression. Our results suggest that a complex regulation of different BMP pathways controls dorso-ventral (DV) patterning from early cleavage stages until somitogenesis.

  3. Invasive fungal infections after natural disasters.

    Science.gov (United States)

    Benedict, Kaitlin; Park, Benjamin J

    2014-03-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed.

  4. Silencing of the Mitogen-Activated Protein Kinases (MAPK) Fus3 and Slt2 in Pseudocercospora fijiensis Reduces Growth and Virulence on Host Plants.

    Science.gov (United States)

    Onyilo, Francis; Tusiime, Geoffrey; Tripathi, Jaindra N; Chen, Li-Hung; Falk, Bryce; Stergiopoulos, Ioannis; Tushemereirwe, Wilberforce; Kubiriba, Jerome; Tripathi, Leena

    2018-01-01

    Pseudocercospora fijiensis , causal agent of the black Sigatoka disease (BSD) of Musa spp., has spread globally since its discovery in Fiji 1963 to all the banana and plantain growing areas across the globe. It is becoming the most damaging and economically important disease of this crop. The identification and characterization of genes that regulate infection processes and pathogenicity in P. fijiensis will provide important knowledge for the development of disease-resistant cultivars. In many fungal plant pathogens, the Fus3 and Slt2 are reported to be essential for pathogenicity. Fus3 regulates filamentous-invasion pathways including the formation of infection structures, sporulation, virulence, and invasive and filamentous growth, whereas Slt2 is involved in the cell-wall integrity pathway, virulence, invasive growth, and colonization in host tissues. Here, we used RNAi-mediated gene silencing to investigate the role of the Slt2 and Fus3 homologs in P. fijiensis in pathogen invasiveness, growth and pathogenicity. The PfSlt2 and PfFus3 silenced P. fijiensis transformants showed significantly lower gene expression and reduced virulence, invasive growth, and lower biomass in infected leaf tissues of East African Highland Banana (EAHB). This study suggests that Slt2 and Fus3 MAPK signaling pathways play important roles in plant infection and pathogenic growth of fungal pathogens. The silencing of these vital fungal genes through host-induced gene silencing (HIG) could be an alternative strategy for developing transgenic banana and plantain resistant to BSD.

  5. Silencing of the Mitogen-Activated Protein Kinases (MAPK Fus3 and Slt2 in Pseudocercospora fijiensis Reduces Growth and Virulence on Host Plants

    Directory of Open Access Journals (Sweden)

    Francis Onyilo

    2018-03-01

    Full Text Available Pseudocercospora fijiensis, causal agent of the black Sigatoka disease (BSD of Musa spp., has spread globally since its discovery in Fiji 1963 to all the banana and plantain growing areas across the globe. It is becoming the most damaging and economically important disease of this crop. The identification and characterization of genes that regulate infection processes and pathogenicity in P. fijiensis will provide important knowledge for the development of disease-resistant cultivars. In many fungal plant pathogens, the Fus3 and Slt2 are reported to be essential for pathogenicity. Fus3 regulates filamentous-invasion pathways including the formation of infection structures, sporulation, virulence, and invasive and filamentous growth, whereas Slt2 is involved in the cell-wall integrity pathway, virulence, invasive growth, and colonization in host tissues. Here, we used RNAi-mediated gene silencing to investigate the role of the Slt2 and Fus3 homologs in P. fijiensis in pathogen invasiveness, growth and pathogenicity. The PfSlt2 and PfFus3 silenced P. fijiensis transformants showed significantly lower gene expression and reduced virulence, invasive growth, and lower biomass in infected leaf tissues of East African Highland Banana (EAHB. This study suggests that Slt2 and Fus3 MAPK signaling pathways play important roles in plant infection and pathogenic growth of fungal pathogens. The silencing of these vital fungal genes through host-induced gene silencing (HIG could be an alternative strategy for developing transgenic banana and plantain resistant to BSD.

  6. Identification of virulence determinants of the human pathogenic fungi Aspergillus fumigatus and Candida albicans by proteomics.

    Science.gov (United States)

    Kniemeyer, Olaf; Schmidt, André D; Vödisch, Martin; Wartenberg, Dirk; Brakhage, Axel A

    2011-06-01

    Both fungi Candida albicans and Aspergillus fumigatus can cause a number of life-threatening systemic infections in humans. The commensal yeast C. albicans is one of the main causes of nosocomial fungal infectious diseases, whereas the filamentous fungus A. fumigatus has become one of the most prevalent airborne fungal pathogens. Early diagnosis of these fungal infections is challenging, only a limited number of antifungals for treatment are available, and the molecular details of pathogenicity are hardly understood. The completion of both the A. fumigatus and C. albicans genome sequence provides the opportunity to improve diagnosis, to define new drug targets, to understand the functions of many uncharacterised proteins, and to study protein regulation on a global scale. With the application of proteomic tools, particularly two-dimensional gel electrophoresis and LC/MS-based methods, a comprehensive overview about the proteins of A. fumigatus and C. albicans present or induced during environmental changes and stress conditions has been obtained in the past 5 years. However, for the discovery of further putative virulence determinants, more sensitive and targeted proteomic methods have to be applied. Here, we review the recent proteome data generated for A. fumigatus and C. albicans that are related to factors required for pathogenicity. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. The Life Cycle of L. pneumophila: Cellular Differentiation Is Linked to Virulence and Metabolism

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    Giulia Oliva

    2018-01-01

    Full Text Available Legionella pneumophila is a gram-negative bacterium that inhabits freshwater ecosystems, where it is present in biofilm or as planktonic form. L. pneumophila is mainly found associated with protozoa, which serve as protection from hostile environments and as replication niche. If inhaled within aerosols, L. pneumophila is also able to infect and replicate in human alveolar macrophages, eventually causing the Legionnaires' disease. The transition between intracellular and extracellular environments triggers a differentiation program in which metabolic as well as morphogenetic changes occur. We here describe the current knowledge on how the different developmental states of this bacterium are regulated, with a particular emphasis on the stringent response activated during the transition from the replicative phase to the infectious phase and the metabolic features going in hand. We propose that the cellular differentiation of this intracellular pathogen is closely associated to key metabolic changes in the bacterium and the host cell, which together have a crucial role in the regulation of L. pneumophila virulence.

  8. Characterization of T-DNA insertion mutants with decreased virulence in the entomopathogenic fungus Beauveria bassiana JEF-007.

    Science.gov (United States)

    Kim, Sihyeon; Lee, Se Jin; Nai, Yu-Shin; Yu, Jeong Seon; Lee, Mi Rong; Yang, Yi-Ting; Kim, Jae Su

    2016-10-01

    The bean bug, Riptortus pedestris, is a major agricultural pest that reduces crop quality and value. Chemical pesticides have contributed to pest management, but resistance to these chemicals has significantly limited their use. Alternative strategies with different modes of action, such as entomopathogenic fungi, are therefore of great interest. Herein, we explored how entomopathogenic fungi can potentially be used to control the bean bug and focused on identifying virulence-related genes. Beauveria bassiana (JEF isolates) were assayed against bean bugs under laboratory conditions. One isolate, JEF-007, showed >80 % virulence by both spray and contact exposure methods. Agrobacterium tumefaciens-mediated transformation (AtMT) of JEF-007 generated 249 random transformants, two of which (B1-06 and C1-49) showed significantly reduced virulence against Tenebrio molitor and R. pedestris immatures. Both species were used for rapid screening of virulence-reduced mutants. The two transformants had different morphologies, conidial production, and thermotolerance than the wild type. To determine the localization of the randomly inserted T-DNA, thermal asymmetric interlaced (TAIL) PCR was conducted and analysis of the two clones found multiple T-DNA insertions (two in B1-06 and three in C1-49). Genes encoding complex I intermediate-associated protein 30 (CIA30) and the autophagy protein (Atg22) were possibly disrupted by the T-DNA insertion and might be involved in the virulence. This work provides a strong platform for future functional genetic studies of bean bug-pathogenic B. bassiana. The genes putatively involved in fungal virulence should be experimentally validated by knockdown in future studies.

  9. LPS structure and PhoQ activity are important for Salmonella Typhimurium virulence in the Galleria mellonella infection model [corrected].

    Directory of Open Access Journals (Sweden)

    Jennifer K Bender

    Full Text Available The larvae of the wax moth, Galleria mellonella, have been used experimentally to host a range of bacterial and fungal pathogens. In this study we evaluated the suitability of G. mellonella as an alternative animal model of Salmonella infection. Using a range of inoculum doses we established that the LD₅₀ of SalmonellaTyphimurium strain NCTC 12023 was 3.6 × 10³ bacteria per larva. Further, a set of isogenic mutant strains depleted of known virulence factors was tested to identify determinants essential for S. Typhimurium pathogenesis. Mutants depleted of one or both of the type III secretion systems encoded by Salmonella Pathogenicity Islands 1 and 2 showed no virulence defect. In contrast, we observed reduced pathogenic potential of a phoQ mutant indicating an important role for the PhoPQ two-component signal transduction system. Lipopolysaccharide (LPS structure was also shown to influence Salmonella virulence in G. mellonella. A waaL(rfaL mutant, which lacks the entire O-antigen (OAg, was virtually avirulent, while a wzz(ST/wzz(fepE double mutant expressing only a very short OAg was highly attenuated for virulence. Furthermore, shortly after infection both LPS mutant strains showed decreased replication when compared to the wild type in a flow cytometry-based competitive index assay. In this study we successfully established a G. mellonella model of S. Typhimurium infection. By identifying PhoQ and LPS OAg length as key determinants of virulence in the wax moth larvae we proved that there is an overlap between this and other animal model systems, thus confirming that the G. mellonella infection model is suitable for assessing aspects of Salmonella virulence function.

  10. Increased virulence of Cunninghamella bertholletiae in experimental pulmonary mucormycosis: correlation with circulating molecular biomarkers, sporangiospore germination and hyphal metabolism.

    Science.gov (United States)

    Petraitis, Vidmantas; Petraitiene, Ruta; Antachopoulos, Charalampos; Hughes, Johanna E; Cotton, Margaret P; Kasai, Miki; Harrington, Susan; Gamaletsou, Maria N; Bacher, John D; Kontoyiannis, Dimitrios P; Roilides, Emmanuel; Walsh, Thomas J

    2013-01-01

    Members of the order Mucorales are emerging invasive molds that cause infections in immunocompromised patients. However, little is known about the relation between different species of Mucorales and their virulence in invasive pulmonary mucormycosis. Based upon our earlier epidemiological studies, we hypothesized that Cunninghamella bertholletiae would demonstrate increased virulence. Therefore, we studied the relative virulence of C. bertholletiae (CB), Rhizopus oryzae (RO), R. microsporus (RM), and Mucor circinelloides (MC) in experimental invasive pulmonary mucormycosis in persistently neutropenic rabbits in relation to the fungi in vitro sporangiospore germination rate and hyphal metabolic activity. Rabbits infected with CB demonstrated (1) higher lung weights in comparison to RM (P ≤ 0.05), RO and MC (P ≤ 0.001), (2) pulmonary infarcts in comparison to RO and MC (P ≤ 0.001), (3) tissue fungal burden (CFU/g) vs. MC (P ≤ 0.001), and (4) the lowest survival of 0% (0/18), in comparison to 16% (3/18, P ≤ 0.01) of RM, 81% (21/26) of RO, and 83% (15/18) of MC-infected rabbits (P ≤ 0.001). Serum PCR concentration-time-curve showed the greatest amplitude for CB. Virulence correlated directly with sporangiospore germination rate at 4 h among species, i.e., CB (67-85%) > RM (14-56%) > RO (4-30%) > MC (0%), and hyphal metabolic activity, i.e., CB (1.22-1.51) > MC (0.54-0.64) = RM (0.38-0.41) = RO (0.37-0.59). C. bertholletiae was significantly more virulent in experimental invasive pulmonary mucormycosis than R. microsporus, R. oryzae, and M. circinelloides. In vivo virulence correlated with species-dependent differences of in vitro germination rate and hyphal metabolic activity.

  11. Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

    Science.gov (United States)

    Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

    2017-09-01

    We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

  12. The Emergence of Cambodian Civil Society within Global Educational Governance: A Morphogenetic Approach to Agency and Structure

    Science.gov (United States)

    Edwards, D. Brent, Jr.; Brehm, William C.

    2015-01-01

    This paper uses Margaret Archer's morphogenetic approach to analyze the emergence of civil society within global educational governance. The purpose is to understand the intersection of historical structures with global actors and spaces that have accompanied the globalization of education. Based on findings from a study on the impact in Cambodia…

  13. Bone Morphogenetic Protein-2, but Not Mesenchymal Stromal Cells, Exert Regenerative Effects on Canine and Human Nucleus Pulposus Cells

    NARCIS (Netherlands)

    Bach, Frances C.; Miranda-Bedate, Alberto; Van Heel, Ferdi W M; Riemers, Frank M.; Müller, Margot C M E; Creemers, Laura B.; Ito, Keita; Benz, Karin; Meij, Björn P.; Tryfonidou, Marianna A.

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  14. Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on canine and human nucleus pulposus cells

    NARCIS (Netherlands)

    Bach, Frances; Miranda-Bedate, Alberto; van Heel, Ferdi; Riemers, Frank; Muller, Margot; Creemers, Laura; Ito, Keita; Benz, Karin; Meij, Björn; Tryfonidou, M

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  15. Bone morphogenetic protein-2, but not mesenchymal stromal cells, exert regenerative effects on Canine and human nucleus pulposus cells

    NARCIS (Netherlands)

    Bach, F.C.; Miranda-Bedate, A.; Van Heel, F.W.M.; Riemers, F.M.; Müller, M.C.M.E.; Creemers, L.B.; Ito, K.; Benz, K.; Meij, B.P.; Tryfonidou, M.A.

    2017-01-01

    Chronic back pain is related to intervertebral disc (IVD) degeneration and dogs are employed as animal models to develop growth factor- and cell-based regenerative treatments. In this respect, the differential effects of transforming growth factor beta-1 (TGF-β1) and bone morphogenetic protein-2

  16. Non-viral bone morphogenetic protein 2 transfection of rat dental pulp stem cells using calcium phosphate nanoparticles as carriers.

    NARCIS (Netherlands)

    Yang, X.; Walboomers, X.F.; Dolder, J. van den; Yang, F.; Bian, Z.; Fan, M.; Jansen, J.A.

    2008-01-01

    Calcium phosphate nanoparticles have shown potential as non-viral vectors for gene delivery. The aim of this study was to induce bone morphogenetic protein (Bmp)2 transfection in rat dental pulp stem cells using calcium phosphate nanoparticles as a gene vector and then to evaluate the efficiency and

  17. Fungal Endocarditis: Update on Diagnosis and Management.

    Science.gov (United States)

    Pasha, Ahmed Khurshid; Lee, Justin Z; Low, See-Wei; Desai, Hem; Lee, Kwan S; Al Mohajer, Mayar

    2016-10-01

    Fungal endocarditis is an extremely debilitating disease associated with high morbidity and mortality. Candida spp. are the most common isolated organisms in fungal endocarditis. It is most prevalent in patients who are immunosuppressed and intravenous drug users. Most patients present with constitutional symptoms, which are indistinguishable from bacterial endocarditis, hence a high index of suspicion is required for pursuing diagnosis. Diagnosis of fungal endocarditis can be very challenging: most of the time, blood cultures are negative or take a long time to yield growth. Fungal endocarditis mandates an aggressive treatment strategy. A medical and surgical combined approach is the cornerstone of therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Unfolded Protein Response (UPR Regulator Cib1 Controls Expression of Genes Encoding Secreted Virulence Factors in Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Martin Hampel

    Full Text Available The unfolded protein response (UPR, a conserved eukaryotic signaling pathway to ensure protein homeostasis in the endoplasmic reticulum (ER, coordinates biotrophic development in the corn smut fungus Ustilago maydis. Exact timing of UPR activation is required for virulence and presumably connected to the elevated expression of secreted effector proteins during infection of the host plant Zea mays. In the baker's yeast Saccharomyces cerevisiae, expression of UPR target genes is induced upon binding of the central regulator Hac1 to unfolded protein response elements (UPREs in their promoters. While a role of the UPR in effector secretion has been described previously, we investigated a potential UPR-dependent regulation of genes encoding secreted effector proteins. In silico prediction of UPREs in promoter regions identified the previously characterized effector genes pit2 and tin1-1, as bona fide UPR target genes. Furthermore, direct binding of the Hac1-homolog Cib1 to the UPRE containing promoter fragments of both genes was confirmed by quantitative chromatin immunoprecipitation (qChIP analysis. Targeted deletion of the UPRE abolished Cib1-dependent expression of pit2 and significantly affected virulence. Furthermore, ER stress strongly increased Pit2 expression and secretion. This study expands the role of the UPR as a signal hub in fungal virulence and illustrates, how biotrophic fungi can coordinate cellular physiology, development and regulation of secreted virulence factors.

  19. Three regulators of G protein signaling differentially affect mating, morphology and virulence in the smut fungus Ustilago maydis.

    Science.gov (United States)

    Moretti, Marino; Wang, Lei; Grognet, Pierre; Lanver, Daniel; Link, Hannes; Kahmann, Regine

    2017-09-01

    Regulators of G protein signaling (RGS) proteins modulate heterotrimeric G protein signaling negatively. To broaden an understanding of the roles of RGS proteins in fungal pathogens, we functionally characterized the three RGS protein-encoding genes (rgs1, rgs2 and rgs3) in the phytopathogenic fungus Ustilago maydis. It was found that RGS proteins played distinct roles in the regulation of development and virulence. rgs1 had a minor role in virulence when deleted in a solopathogenic strain. In crosses, rgs1 was dispensable for mating and filamentation, but was required for teliospore production. Haploid rgs2 mutants were affected in cell morphology, growth, mating and were unable to cause disease symptoms in crosses. However, virulence was unaffected when rgs2 was deleted in a solopathogenic strain, suggesting an exclusive involvement in pre-fusion events. These rgs2 phenotypes are likely connected to elevated intracellular cAMP levels. rgs3 mutants were severely attenuated in mating, in their response to pheromone, virulence and formation of mature teliospores. The mating defect could be traced back to reduced expression of the transcription factor rop1. It was speculated that the distinct roles of the three U. maydis RGS proteins were achieved by direct modulation of the Gα subunit-activated signaling pathways as well as through Gα-independent functions. © 2017 John Wiley & Sons Ltd.

  20. FvSTR1, a striatin orthologue in Fusarium virguliforme, is required for asexual development and virulence.

    Science.gov (United States)

    Islam, Kazi T; Bond, Jason P; Fakhoury, Ahmad M

    2017-08-01

    The soil-borne fungus Fusarium virguliforme causes sudden death syndrome (SDS), one of the most devastating diseases of soybean in North and South America. Despite the importance of SDS, a clear understanding of the fungal pathogenicity factors that affect the development of this disease is still lacking. We have identified FvSTR1, a F. virguliforme gene, which encodes a protein similar to a family of striatin proteins previously reported to regulate signalling pathways, cell differentiation, conidiation, sexual development, and virulence in filamentous fungi. Striatins are multi-domain proteins that serve as scaffolding units in the striatin-interacting phosphatase and kinase (STRIPAK) complex in fungi and animals. To address the function of a striatin homologue in F. virguliforme, FvSTR1 was disrupted and functionally characterized using a gene knock out strategy. The resulting Fvstr1 mutants were largely impaired in conidiation and pigmentation, and displayed defective conidia and conidiophore morphology compared to the wild-type and ectopic transformants. Greenhouse virulence assays revealed that the disruption of FvSTR1 resulted in complete loss of virulence in F. virguliforme. Microtome studies using fluorescence microscopy showed that the Fvstr1 mutants were defective in their ability to colonize the vascular system. The Fvstr1 mutants also showed a reduced transcript level of genes involved in asexual reproduction and in the production of secondary metabolites. These results suggest that FvSTR1 has a critical role in asexual development and virulence in F. virguliforme.

  1. Knocking out Bcsas1 in Botrytis cinerea impacts growth, development, and secretion of extracellular proteins, which decreases virulence.

    Science.gov (United States)

    Zhang, Zhanquan; Qin, Guozheng; Li, Boqiang; Tian, Shiping

    2014-06-01

    Pathogenic fungi usually secrete a series of virulence factors to the extracellular environment to facilitate infection. Rab GTPases play a central role in the secretory pathway. To explore the function of Rab/GTPase in filamentous fungi, we knocked out a Rab/GTPase family gene, Bcsas1, in Botrytis cinerea, an aggressive fungal pathogen that infects more than 200 plant species. A detailed analysis was conducted on the virulence and the secretory capability of the mutants. The results indicated that knockout of Bcsas1 inhibited hyphal development and reduced sporulation of B. cinerea on potato dextrose agar plates resulting in reduced virulence on various fruit hosts. Knocking out the Bcsas1 gene led to an accumulation of transport vesicles at the hyphal tip, significantly reduced extracellular protein content, and lowered the activity of polygalacturonase and xylanase in the extracellular medium. However, mutation of Bcsas1 did not affect the expression of genes encoding polygalacturonase and xylanase, suggesting the secretion of these two family enzymes was suppressed in the mutant. Moreover, a comparative analysis of the secretome provided further evidence that the disruption of Bcsas1 in mutant strains significantly depressed the secretion of polysaccharide hydrolases and proteases. The results indicate that Bcsas1, the Rab8/SEC4-like gene, plays a crucial role in development, protein secretion, and virulence of B. cinerea.

  2. Polyketide synthases of Diaporthe helianthi and involvement of DhPKS1 in virulence on sunflower.

    Science.gov (United States)

    Ruocco, Michelina; Baroncelli, Riccardo; Cacciola, Santa Olga; Pane, Catello; Monti, Maurilia Maria; Firrao, Giuseppe; Vergara, Mariarosaria; Magnano di San Lio, Gaetano; Vannacci, Giovanni; Scala, Felice

    2018-01-06

    The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D. helianthi population. In order to investigate the role of polyketide synthases in D. helianthi 7/96, a draft genome of this isolate was examined. We were able to find and phylogenetically analyse 40 genes putatively coding for polyketide synthases (PKSs). Analysis of their domains revealed that most PKS genes of D. helianthi are reducing PKSs, whereas only eight lacked reducing domains. Most of the identified PKSs have orthologs shown to be virulence factors or genetic determinants for toxin production in other pathogenic fungi. One of the genes (DhPKS1) corresponded to the previously cloned D. helianthi lovB gene fragment and clustered with a nonribosomal peptide synthetase (NRPS) -PKS hybrid/lovastatin nonaketide like A. nidulans LovB. We used DhPKS1 as a case study and carried out its disruption through Agrobacterium-mediated transformation in the isolate 7/96. D. helianthi DhPKS1 deleted mutants were less virulent to sunflower compared to the wild type, indicating a role for this gene in the pathogenesis of the fungus. The PKS sequences analysed and reported here constitute a new genomic resource that will be useful for further research on the biology, ecology and evolution of D. helianthi and generally of fungal plant pathogens.

  3. Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections.

    Science.gov (United States)

    de Souza, Patrícia Canteri; Morey, Alexandre Tadachi; Castanheira, Gabriel Marcondes; Bocate, Karla Paiva; Panagio, Luciano Aparecido; Ito, Fabio Augusto; Furlaneto, Márcia Cristina; Yamada-Ogatta, Sueli Fumie; Costa, Idessânia Nazareth; Mora-Montes, Hector Manuel; Almeida, Ricardo Sergio

    2015-11-01

    Models of host–pathogen interactions are crucial for the analysis of microbial pathogenesis. In this context, invertebrate hosts, including Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode) and Galleria mellonella (moth), have been used to study the pathogenesis of fungi and bacteria. Each of these organisms offers distinct benefits in elucidating host–pathogen interactions. In this study,we present a newinvertebrate infection model to study fungal infections: the Tenebrio molitor (beetle) larvae. Here we performed T. molitor larvae infection with one of two important fungal human pathogens, Candida albicans or Cryptococcus neoformans, and analyzed survival curves and larva infected tissues.We showed that increasing concentrations of inoculum of both fungi resulted in increased mortality rates, demonstrating the efficiency of the method to evaluate the virulence of pathogenic yeasts. Additionally, following 12 h post-infection, C. albicans formsmycelia, spreading its hyphae through the larva tissue,whilst GMS stain enabled the visualization of C. neoformans yeast and theirmelanin capsule. These larvae are easier to cultivate in the laboratory than G. mellonella larvae, and offer the same benefits. Therefore, this insect model could be a useful alternative tool to screen clinical pathogenic yeast strainswith distinct virulence traits or different mutant strains.

  4. FvSet2 regulates fungal growth, pathogenicity, and secondary metabolism in Fusarium verticillioides.

    Science.gov (United States)

    Gu, Qin; Wang, Zhenzhong; Sun, Xiao; Ji, Tiantian; Huang, Hai; Yang, Yang; Zhang, Hao; Tahir, Hafiz Abdul Samad; Wu, Liming; Wu, Huijun; Gao, Xuewen

    2017-10-01

    Histone H3 lysine 36 methylation (H3K36me) is generally associated with activation of gene expression in most eukaryotic cells. However, the function of H3K36me in filamentous fungi is largely unknown. Set2 is the sole lysine histone methyltransferase (KHMTase) enzyme responsible for the methylation of H3K36 in Saccharomyces cerevisiae. In the current study, we identified a single ortholog of S. cerevisiae Set2 in Fusarium verticillioides. We report that FvSet2 is responsible for the trimethylation of H3K36 (H3K36me3). The FvSET2 deletion mutant (ΔFvSet2) showed significant defects in vegetative growth, FB 1 biosynthesis, pigmentation, and fungal virulence. Furthermore, trimethylation of H3K36 was found to be important for active transcription of genes involved in FB 1 and bikaverin biosyntheses. These data indicate that FvSet2 plays an important role in the regulation of secondary metabolism, vegetative growth and fungal virulence in F. verticillioides. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Recombinant human bone morphogenetic protein 2 in augmentation procedures: case reports.

    Science.gov (United States)

    Luiz, Jaques; Padovan, Luis Eduardo Marques; Claudino, Marcela

    2014-01-01

    To successfully rehabilitate edentulous patients using endosseous implants, there must be enough available bone. Several techniques have been proposed for augmentation of sites with insufficient bone volume. Although autogenous bone has long been considered the gold standard for such procedures, the limited availability of graft material and a high morbidity rate are potential disadvantages of this type of graft. An alternative is to use recombinant human bone morphogenetic protein 2 (rhBMP-2), which is able to support bone regeneration in the oral environment. These cases demonstrate the applicability of rhBMP-2 in maxillary sinus elevation and augmentation procedures in the maxilla to enable dental implant placement. The use of rhBMP-2 in alveolar augmentation procedures had several clinical benefits for these patients.

  6. Morphogenetic Alterations in Melipona quadrifasciata anthidioides (Hymenoptera: Apidae) Associated with Pesticides.

    Science.gov (United States)

    Prado-Silva, Arlete; Nunes, Lorena Andrade; Dos Santos, Jádilla Mendes; Affonso, Paulo Roberto Antunes de Mello; Waldschmidt, Ana Maria

    2018-05-01

    Bees are major pollinators of both native flora and cultured crops. Nonetheless, despite their key functional role in ecosystems and agriculture, bee populations have been affected worldwide by deforestation and contamination by insecticides. Conversely, little is known about the effects of pesticides on morphogenetic development of neotropical stingless bees. We compared the fluctuating asymmetry (FA) in newly emerged bees and foragers of Melipona quadrifasciata anthidioides exposed to pesticides (experimental greenhouse and cultivated field). In addition, visitation behavior of foragers was inferred from pollen analyses and direct observation. A significant increase of FA (P < 0.001) was detected in bees from the greenhouse. Even though pesticides might affect their development, foragers seem to avoid contaminated plants whenever possible, as confirmed by pollen and visitation analyses. Consequently, the conservation of natural forests in agricultural landscapes is essential to ensure the health of colonies in stingless bees.

  7. Correlation between the morphogenetic types of litter and their properties in bog birch forests

    Science.gov (United States)

    Efremova, T. T.; Efremov, S. P.; Avrova, A. F.

    2010-08-01

    A formalized arrangement of morphogenetic types of litter according to the physicochemical parameters provided their significant grouping in three genetic associations. The litter group (highly decomposed + moderately decomposed) is confined to the tall-grass group of bog birch forests. The rhizomatous (roughly decomposed) litter is formed in the sedge-reed grass bog birch forests. The litter group (peaty + peatified + peat) is associated with the bog-herbaceous-moss group of forest types. The genetic associations of the litters (a) reliably characterize the edaphic conditions of bog birch forests and (b)correspond to formation of the peat of certain ecological groups. We found highly informative the acid-base parameters, the exchangeable cations (Ca2+ + Mg2+) and the total potential acidity, which differentiated the genetic associations of litter practically with 100% probability. The expediency of studying litters under groups of forest types rather than under separate types of bog birch forests was demonstrated.

  8. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Science.gov (United States)

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  9. Productive and morphogenetic responses of buffel grass at different air temperatures and CO2 concentrations

    Directory of Open Access Journals (Sweden)

    Roberta Machado Santos

    2014-08-01

    Full Text Available The objective of the present trial was to evaluate the productive and morphogenetic characteristics of buffel grass subjected to different air temperatures and CO2 concentrations. Three cultivars of buffel grass (Biloela, Aridus and West Australian were compared. Cultivars were grown in growth chambers at three temperatures (day/night: 26/20, 29/23, and 32/26 °C, combined with two concentrations of CO2: 370 and 550 µmol mol-1. The experimental design was completely randomized, in a 3 × 3 × 2 factorial arrangement with three replications. There were interactions between buffel grass cultivars and air temperatures on leaf elongation rate (LER, leaf appearance rate (LAR, leaf lifespan (LL and senescence rate (SR, whereas cultivars vs. carbon dioxide concentration affected forage mass (FM, root mass (RM, shoot/root ratio, LL and SR. Leaf elongation rate and SR were higher as the air temperature was raised. Increasing air temperature also promoted an increase in LAR, except for West Australian. High CO2 concentration provided greater SR of plants, except for Biloela. Cultivar West Australian had higher FM in relation to Biloela and Aridus when the CO2 concentration was increased to 550 µmol mol-1. West Australian was the only cultivar that responded with more forage mass when it was exposed to higher carbon dioxide concentrations, whereas Aridus had depression in forage mass. The increase in air temperatures affects morphogenetic responses of buffel grass, accelerating its vegetative development without increasing forage mass. Elevated carbon dioxide concentration changes productive responses of buffel grass.

  10. Survey of the Effectiveness of Internet Information on Patient Education for Bone Morphogenetic Protein.

    Science.gov (United States)

    Huang, Meng; Briceño, Valentina; Lam, Sandi K; Luerssen, Thomas G; Jea, Andrew

    2016-03-01

    In light of recent reports of potential short- and long-term complications of bone morphogenetic protein (BMP) and increasing "off-label" use among spine surgeons, we wished to analyze online information on BMP and its controversial uses, as patients frequently search the Internet for medical information, even though the quality and accuracy of available information are highly variable. Between December 2014 and January 2015, we conducted a Google search to identify the 50 most accessed websites providing BMP information using the search phrase "bone morphogenetic protein." Websites were classified based on authorship. Each website was examined for the provision of appropriate patient inclusion and exclusion criteria, surgical and nonsurgical treatment alternatives, purported benefits, disclosure of common and potential complications, peer-reviewed literature citations, and discussion of off-label use. Two percent of websites were authored by private medical groups, 2% by academic medical groups, 10% by insurance companies, 16% by biomedical industries, 4% by news sources, 0% by lawyers, and 66% by others. Sixty-two percent referenced peer-reviewed literature. Benefits and complications were reported in 44% and 26% of websites, respectively. Surgical and nonsurgical treatment alternatives were mentioned in 16% and 4% of websites, respectively. Discussion of off-label BMP use occurred in 18% of websites. Our study showed the ineffectiveness of the Internet in reporting quality information on BMP use. We found that websites authored by insurance companies provide an acceptable foundation for patient education. This, however, cannot replace the need for a thorough dialogue between doctor and patient about risks, benefits, and indications. Copyright © 2016. Published by Elsevier Inc.

  11. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

    Directory of Open Access Journals (Sweden)

    La WG

    2014-05-01

    Full Text Available Wan-Geun La,1 Min Jin,1 Saibom Park,1,2 Hee-Hun Yoon,1 Gun-Jae Jeong,1 Suk Ho Bhang,1 Hoyoung Park,1,2 Kookheon Char,1,2 Byung-Soo Kim1,31School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea; 2The National Creative Research Initiative Center for Intelligent Hybrids, Seoul National University, Seoul, Republic of Korea; 3Institute of Bioengineering, Institute of Chemical Processes, Engineering Research Institute, Seoul National University, Seoul, Republic of KoreaAbstract: In this study, we demonstrate that graphene oxide (GO can be used for the delivery of bone morphogenetic protein-2 (BMP-2 and substance P (SP, and that this delivery promotes bone formation on titanium (Ti implants that are coated with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2 delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit mesenchymal stem cells (MSCs, was co-delivered using Ti or GO-coated Ti to further promote bone formation. SP induced the migration of MSCs in vitro. The dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone formation on Ti implanted in the mouse calvaria compared with other groups. This approach may be useful to improve osteointegration of Ti in dental or orthopedic implants.Keywords: bone morphogenetic protein-2, bone regeneration, graphene oxides, stem cell recruitment, substance P

  12. Compatibility in the Ustilago maydis-maize interaction requires inhibition of host cysteine proteases by the fungal effector Pit2.

    Directory of Open Access Journals (Sweden)

    André N Mueller

    2013-02-01

    Full Text Available The basidiomycete Ustilago maydis causes smut disease in maize, with large plant tumors being formed as the most prominent disease symptoms. During all steps of infection, U. maydis depends on a biotrophic interaction, which requires an efficient suppression of plant immunity. In a previous study, we identified the secreted effector protein Pit2, which is essential for maintenance of biotrophy and induction of tumors. Deletion mutants for pit2 successfully penetrate host cells but elicit various defense responses, which stops further fungal proliferation. We now show that Pit2 functions as an inhibitor of a set of apoplastic maize cysteine proteases, whose activity is directly linked with salicylic-acid-associated plant defenses. Consequently, protease inhibition by Pit2 is required for U. maydis virulence. Sequence comparisons with Pit2 orthologs from related smut fungi identified a conserved sequence motif. Mutation of this sequence caused loss of Pit2 function. Consequently, expression of the mutated protein in U. maydis could not restore virulence of the pit2 deletion mutant, indicating that the protease inhibition by Pit2 is essential for fungal virulence. Moreover, synthetic peptides of the conserved sequence motif showed full activity as protease inhibitor, which identifies this domain as a new, minimal protease inhibitor domain in plant-pathogenic fungi.

  13. Fungal transmission of plant viruses.

    Science.gov (United States)

    Campbell, R N

    1996-01-01

    Thirty soilborne viruses or virus-like agents are transmitted by five species of fungal vectors. Ten polyhedral viruses, of which nine are in the family Tombusviridae, are acquired in the in vitro manner and do not occur within the resting spores of their vectors, Olpidium brassicae and O. bornovanus. Fungal vectors for other viruses in the family should be sought even though tombusviruses are reputed to be soil transmitted without a vector. Eighteen rod-shaped viruses belonging to the furo- and bymovirus groups and to an unclassified group are acquired in the in vivo manner and survive within the resting spores of their vector, O. brassicae, Polymyxa graminis, P. betae, and Spongospora subterranea. The viral coat protein has an essential role in in vitro transmission. With in vivo transmission a site in the coat protein-read through protein (CP-RT) of beet necrotic yellow vein furovirus determines vector transmissibility as does a site in a similar 98-kDa polyprotein of barley mild mosaic bymovirus. The mechanisms by which virions move (or are moved) into and out of the protoplasm of zoospores or of thalli needs study.

  14. Optimal Fungal Space Searching Algorithms.

    Science.gov (United States)

    Asenova, Elitsa; Lin, Hsin-Yu; Fu, Eileen; Nicolau, Dan V; Nicolau, Dan V

    2016-10-01

    Previous experiments have shown that fungi use an efficient natural algorithm for searching the space available for their growth in micro-confined networks, e.g., mazes. This natural "master" algorithm, which comprises two "slave" sub-algorithms, i.e., collision-induced branching and directional memory, has been shown to be more efficient than alternatives, with one, or the other, or both sub-algorithms turned off. In contrast, the present contribution compares the performance of the fungal natural algorithm against several standard artificial homologues. It was found that the space-searching fungal algorithm consistently outperforms uninformed algorithms, such as Depth-First-Search (DFS). Furthermore, while the natural algorithm is inferior to informed ones, such as A*, this under-performance does not importantly increase with the increase of the size of the maze. These findings suggest that a systematic effort of harvesting the natural space searching algorithms used by microorganisms is warranted and possibly overdue. These natural algorithms, if efficient, can be reverse-engineered for graph and tree search strategies.

  15. Potential drivers of virulence evolution in aquaculture

    Science.gov (United States)

    Kennedy, David A.; Kurath, Gael; Brito, Ilana L.; Purcell, Maureen K.; Read, Andrew F.; Winton, James R.; Wargo, Andrew R.

    2016-01-01

    Infectious diseases are economically detrimental to aquaculture, and with continued expansion and intensification of aquaculture, the importance of managing infectious diseases will likely increase in the future. Here, we use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence. We identify eight practices common in aquaculture that theory predicts may favor evolution toward higher pathogen virulence. Four are related to intensive aquaculture operations, and four others are related specifically to infectious disease control. Our intention is to make aquaculture managers aware of these risks, such that with increased vigilance, they might be able to detect and prevent the emergence and spread of increasingly troublesome pathogen strains in the future.

  16. Virulence factors of the Mycobacterium tuberculosis complex

    Science.gov (United States)

    Forrellad, Marina A.; Klepp, Laura I.; Gioffré, Andrea; Sabio y García, Julia; Morbidoni, Hector R.; Santangelo, María de la Paz; Cataldi, Angel A.; Bigi, Fabiana

    2013-01-01

    The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world. PMID:23076359

  17. Glucose starvation boosts Entamoeba histolytica virulence.

    Directory of Open Access Journals (Sweden)

    Ayala Tovy

    2011-08-01

    Full Text Available The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS. The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP, a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1 which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A and cysteine proteinase A5 (CP-A5, two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon.

  18. Fungal effector proteins: past, present and future

    NARCIS (Netherlands)

    Wit, de P.J.G.M.; Mehrabi, R.; Burg, van den H.A.; Stergiopoulos, I.

    2009-01-01

    The pioneering research of Harold Flor on flax and the flax rust fungus culminated in his gene-for-gene hypothesis. It took nearly 50 years before the first fungal avirulence (Avr) gene in support of his hypothesis was cloned. Initially, fungal Avr genes were identified by reverse genetics and

  19. A novel class of fungal lipoxygenases

    NARCIS (Netherlands)

    Heshof, R.; Jylhä, S.; Haarmann, T.; Jørgensen, A.L.W.; Dalsgaard, T.K.; Graaff, de L.H.

    2014-01-01

    Lipoxygenases (LOXs) are well-studied enzymes in plants and mammals. However, fungal LOXs are less studied. In this study, we have compared fungal LOX protein sequences to all known characterized LOXs. For this, a script was written using Shell commands to extract sequences from the NCBI database

  20. Fungal infection knowledge gap in Ethiopia

    African Journals Online (AJOL)

    EPHA USER33

    receiving immunosuppressive therapy, and patients with chronic obstructive lung disease (1). Fungi also play a role in allergic fungal disease such as allergic broncho- pulmonary Aspergilosis (ABPA) and chronic or deep tissue infections. The laboratory diagnosis of fungal infection starts with a simple potassium hydroxide.

  1. Clinical consideration of fungal paranasal sinusitis

    International Nuclear Information System (INIS)

    Okuni, Tsuyoshi; Asakura, Koji; Homma, Tomo; Kawaguchi, Ryuichi; Ishikawa, Tadataka; Yamazaki, Norikazu; Himi, Tetsuo

    2008-01-01

    Fungal paranasal sinusitis is included in the differential diagnosis of unilateral paranasal lesion. Recently the incidence of fungal paranasal sinusitis has been increasing. We reviewed 24 patients (9 males and 15 females) with fungal paranasal sinusitis treated at Muroran City Hospital between January 2001 and May 2006, and clinical presentation and CT findings with those of 56 patients (36 males and 20 females) with chronic unilateral sinusitis. Fungal sinusitis patients ranged in age from 45 to 87, and the average age was 65.9 years old. In contrast, the age of chronic sinusitis patients ranged from 24 to 83, and the average age was 54.4 years old. The chief complaint of both fungal sinusitis and chronic sinusitis included rhinorrhea, nasal obstruction and post nasal discharge. CT exam was performed in all patients. In 23 cases of paranasal fungal sinusitis and 54 cases of chronic sinusitis the findings involved the maxillary sinus. The most common observation (69.6%) was bone density within the affected sinus in fungal sinusitis. However, only 2 cases of chronic sinusitis (3.9%) showed calcification. All cases of fungal sinusitis were diagnosed by pathological examinations. Most cases were proved to be aspergillus, while only one case was mucor. We treated all cases surgically, 18 cases underwent Caldwell-Luc's procedure and 5 cases underwent endoscopic sinus surgery under local anesthesia. (author)

  2. Fungal cultivation on glass-beads

    DEFF Research Database (Denmark)

    Droce, Aida; Sørensen, Jens Laurids; Giese, Henriette

    Transcription of various bioactive compounds and enzymes are dependent on fungal cultivation method. In this study we cultivate Fusarium graminearum and Fusarium solani on glass-beads with liquid media in petri dishes as an easy and inexpensive cultivation method, that resembles in secondary...... metabolite production to agar-cultivation but with an easier and more pure RNA-extraction of total fungal mycelia....

  3. Histone Acetylation in Fungal Pathogens of Plants

    Directory of Open Access Journals (Sweden)

    Junhyun Jeon

    2014-03-01

    Full Text Available Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed.

  4. Soil fungal community responses to global changes

    DEFF Research Database (Denmark)

    Haugwitz, Merian Skouw

    Global change will affect the functioning and structure of terrestrial ecosystems and since soil fungi are key players in organic matter decomposition and nutrient turnover, shifts in fungal community composition might have a strong impact on soil functioning. The main focus of this thesis...... was therefore to investigate the impact of global environmental changes on soil fungal communities in a temperate and subartic heath ecosystem. The objective was further to determine global change effects on major functional groups of fungi and analyze the influence of fungal community changes on soil carbon...... and nutrient availability and storage. By combining molecular methods such as 454 pyrosequencing and quantitative PCR of fungal ITS amplicons with analyses of soil enzymes, nutrient pools of carbon, nitrogen and phosphorus we were able to characterize soil fungal communities as well as their impact on nutrient...

  5. Population dynamics of the critically endangered toad Atelopus cruciger and the fungal disease chytridiomycosis

    Science.gov (United States)

    Señaris, Celsa; García, Carmen Zulay

    2017-01-01

    Harlequin toads (Atelopus) are among the most severely impacted amphibians by the emergence of chytridiomycosis, a fungal disease caused by the pathogen Batrachochytrium dendrobatidis (Bd). Many species disappeared while others suffered drastic contractions of their geographic distribution to lower altitudes. A diminished virulence of Bd in warm habitats was proposed to explain the survival of lowland populations of harlequin toads (i.e. thermal refuge hypothesis). To understand the mechanisms that allow some populations to reach an endemic equilibrium with this pathogen, we estimated demographic and epidemiological parameters at one remnant population of Atelopus cruciger in Venezuela using mark-recapture data from 2007–2013. We demonstrated that Bd is highly virulent for A. cruciger, increasing the odds of dying of infected adults four times in relation to uninfected ones and reducing the life expectancy of reproductive toads to a few weeks. Despite an estimated annual loss of 18% of the reproductive population due to Bd-induced mortality, this population has persisted in an endemic equilibrium for the last decade through the large recruitment of healthy adults every year. Given the high vulnerability of harlequin toads to Bd in lowland populations, thermal refuges need to be redefined as habitats of reduced transmission rather than attenuated virulence. PMID:28570689

  6. Mp1p Is a Virulence Factor in Talaromyces (Penicillium marneffei.

    Directory of Open Access Journals (Sweden)

    Patrick C Y Woo

    2016-08-01

    Full Text Available Talaromyces marneffei is an opportunistic dimorphic fungus prevalent in Southeast Asia. We previously demonstrated that Mp1p is an immunogenic surface and secretory mannoprotein of T. marneffei. Since Mp1p is a surface protein that can generate protective immunity, we hypothesized that Mp1p and/or its homologs are virulence factors.We examined the pathogenic roles of Mp1p and its homologs in a mouse model. All mice died 21 and 30 days after challenge with wild-type T. marneffei PM1 and MP1 complemented mutant respectively. None of the mice died 60 days after challenge with MP1 knockout mutant (P<0.0001. Seventy percent of mice died 60 days after challenge with MP1 knockdown mutant (P<0.0001. All mice died after challenge with MPLP1 to MPLP13 knockdown mutants, suggesting that only Mp1p plays a significant role in virulence. The mean fungal loads of PM1 and MP1 complemented mutant in the liver, lung, kidney and spleen were significantly higher than those of the MP1 knockout mutant. Similarly, the mean load of PM1 in the liver, lung and spleen were significantly higher than that of the MP1 knockdown mutant. Histopathological studies showed an abundance of yeast in the kidney, spleen, liver and lung with more marked hepatic and splenic necrosis in mice challenged with PM1 compared to MP1 knockout and MP1 knockdown mutants. Likewise, a higher abundance of yeast was observed in the liver and spleen of mice challenged with MP1 complemented mutant compared to MP1 knockout mutant. PM1 and MP1 complemented mutant survived significantly better than MP1 knockout mutant in macrophages at 48 hours (P<0.01 post-infection. The mean fungal counts of Pichia pastoris GS115-MP1 in the liver (P<0.001 and spleen (P<0.05 of mice were significantly higher than those of GS115 at 24 hours post-challenge.Mp1p is a key virulence factor of T. marneffei. Mp1p mediates virulence by improving the survival of T. marneffei in macrophages.

  7. INCIDENCE OF FUNGAL ELEMENTS IN SINONASAL POLYPOSIS

    Directory of Open Access Journals (Sweden)

    Santhosh G. S

    2016-12-01

    Full Text Available BACKGROUND Nasal polyposis is a disease entity characterised by formation of pseudoedema of sinonasal mucus membrane progressing to form polyps. It presents clinically with nasal obstruction and fleshy masses in the nasal cavity. The nasal mucosa reacts to formation of polypi in allergic fungal sinusitis also. The present study is an attempt to demonstrate possible fungal elements from the polypi removed during surgery by KOH study and HPE study. The aim of the study is to find out the incidence of fungal elements in sinonasal polyposis. MATERIALS AND METHODS 50 patients attending the ENT OPD for nasal obstruction and showing polypi on anterior rhinoscopy were selected. All the patients were subjected to surgery and specimens collected were subjected to KOH study and histopathology to demonstrate fungal elements. RESULTS Among 50 patients, the age range was from 9-57 years; mean age- 36.46 years. The male-to-female ratio was 1.5:1. Deviated nasal septum was found in 38% of patients. Among the unilateral cases, 47% were antrochoanal polyps and 53% were ethmoid polyps. Out of 50 patients, only 3 specimens were positive for fungal elements with KOH study and only 2 cases with fungal culture. Thus, the incidence of fungal elements in sinonasal polyposis was 6%. CONCLUSION The incidence of fungal elements in sinonasal polyposis was 6%. Histopathological examination of polypectomy specimen was negative for invasive fungal disease and showed inflammatory changes only. There is no difference in the detection of the presence of fungal by two methods.

  8. Chapter 8: Invasive fungal rhinosinusitis.

    Science.gov (United States)

    Duggal, Praveen; Wise, Sarah K

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  9. The Toxin and Virulence Database: A Resource for Signature Development and Analysis of Virulence

    National Research Council Canada - National Science Library

    Wolinsky, Murray A

    2004-01-01

    In this joint effort with the University of Alabama at Birmingham, Walter Reed, MITRE and USAMRIID, we are developing a comprehensive database for microbial toxins and virulence factors (www.tvfac.lanl.gov...

  10. Mechanisms of disease: Helicobacter pylori virulence factors.

    Science.gov (United States)

    Yamaoka, Yoshio

    2010-11-01

    Helicobacter pylori plays an essential role in the development of various gastroduodenal diseases; however, only a small proportion of people infected with H. pylori develop these diseases. Some populations that have a high prevalence of H. pylori infection also have a high incidence of gastric cancer (for example, in East Asia), whereas others do not (for example, in Africa and South Asia). Even within East Asia, the incidence of gastric cancer varies (decreasing in the south). H. pylori is a highly heterogeneous bacterium and its virulence varies geographically. Geographic differences in the incidence of gastric cancer can be explained, at least in part, by the presence of different types of H. pylori virulence factor, especially CagA, VacA and OipA. However, it is still unclear why the pathogenicity of H. pylori increased as it migrated from Africa to East Asia during the course of evolution. H. pylori infection is also thought to be involved in the development of duodenal ulcer, which is at the opposite end of the disease spectrum to gastric cancer. This discrepancy can be explained in part by the presence of H. pylori virulence factor DupA. Despite advances in our understanding of the development of H. pylori-related diseases, further work is required to clarify the roles of H. pylori virulence factors.

  11. Efflux inhibitor suppresses Streptococcus mutans virulence properties.

    Science.gov (United States)

    Zeng, Huihui; Liu, Jia; Ling, Junqi

    2017-04-01

    It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Microbial virulence and interactions with metals

    DEFF Research Database (Denmark)

    German, N.; Lüthje, Freja Lea; Hao, X.

    2016-01-01

    Transition metals, such as iron, copper, zinc, and manganese play an important role in many bacterial biological processes that add to an overall evolutional fitness of bacteria. They are often involved in regulation of bacterial virulence as a mechanism of host invasion. However, the same transi...

  13. NEW VIRULENCE FACTORS OF STREPTOCOCCUS PNEUMONIAE

    NARCIS (Netherlands)

    Hermans, Peter Wilhelmus Maria; Bootsma, Jeanette Hester; Burghout, Pieter Jan; Kuipers, Oscar; Bijlsma, Johanna Jacoba Elisabeth; Kloosterman, Tomas Gerrit; Andersen, Christian O.

    2011-01-01

    The present invention provides proteins/genes, which are essential for survival, and consequently, for virulence of Streptococcus pneumoniae in vivo, and thus are ideal vaccine candidates for a vaccine preparation against pneumococcal infection. Further, also antibodies against said protein(s) are

  14. Global distribution of two fungal pathogens threatening endangered sea turtles.

    Science.gov (United States)

    Sarmiento-Ramírez, Jullie M; Abella-Pérez, Elena; Phillott, Andrea D; Sim, Jolene; van West, Pieter; Martín, María P; Marco, Adolfo; Diéguez-Uribeondo, Javier

    2014-01-01

    Nascent fungal infections are currently considered as one of the main threats for biodiversity and ecosystem health, and have driven several animal species into critical risk of extinction. Sea turtles are one of the most endangered groups of animals and only seven species have survived to date. Here, we described two pathogenic species, i.e., Fusarium falciforme and Fusarium keratoplasticum, that are globally distributed in major turtle nesting areas for six sea turtle species and that are implicated in low hatch success. These two fungi possess key biological features that are similar to emerging pathogens leading to host extinction, e.g., high virulence, and a broad host range style of life. Their optimal growth temperature overlap with the optimal incubation temperature for eggs, and they are able to kill up to 90% of the embryos. Environmental forcing, e.g., tidal inundation and clay/silt content of nests, were correlated to disease development. Thus, these Fusarium species constitute a major threat to sea turtle nests, especially to those experiencing environmental stressors. These findings have serious implications for the survival of endangered sea turtle populations and the success of conservation programs worldwide.

  15. Global distribution of two fungal pathogens threatening endangered sea turtles.

    Directory of Open Access Journals (Sweden)

    Jullie M Sarmiento-Ramírez

    Full Text Available Nascent fungal infections are currently considered as one of the main threats for biodiversity and ecosystem health, and have driven several animal species into critical risk of extinction. Sea turtles are one of the most endangered groups of animals and only seven species have survived to date. Here, we described two pathogenic species, i.e., Fusarium falciforme and Fusarium keratoplasticum, that are globally distributed in major turtle nesting areas for six sea turtle species and that are implicated in low hatch success. These two fungi possess key biological features that are similar to emerging pathogens leading to host extinction, e.g., high virulence, and a broad host range style of life. Their optimal growth temperature overlap with the optimal incubation temperature for eggs, and they are able to kill up to 90% of the embryos. Environmental forcing, e.g., tidal inundation and clay/silt content of nests, were correlated to disease development. Thus, these Fusarium species constitute a major threat to sea turtle nests, especially to those experiencing environmental stressors. These findings have serious implications for the survival of endangered sea turtle populations and the success of conservation programs worldwide.

  16. Nutrient Sensing at the Plasma Membrane of Fungal Cells.

    Science.gov (United States)

    Van Dijck, Patrick; Brown, Neil Andrew; Goldman, Gustavo H; Rutherford, Julian; Xue, Chaoyang; Van Zeebroeck, Griet

    2017-03-01

    To respond to the changing environment, cells must be able to sense external conditions. This is important for many processes including growth, mating, the expression of virulence factors, and several other regulatory effects. Nutrient sensing at the plasma membrane is mediated by different classes of membrane proteins that activate downstream signaling pathways: nontransporting receptors, transceptors, classical and nonclassical G-protein-coupled receptors, and the newly defined extracellular mucin receptors. Nontransporting receptors have the same structure as transport proteins, but have lost the capacity to transport while gaining a receptor function. Transceptors are transporters that also function as a receptor, because they can rapidly activate downstream signaling pathways. In this review, we focus on these four types of fungal membrane proteins. We mainly discuss the sensing mechanisms relating to sugars, ammonium, and amino acids. Mechanisms for other nutrients, such as phosphate and sulfate, are discussed briefly. Because the model yeast Saccharomyces cerevisiae has been the most studied, especially regarding these nutrient-sensing systems, each subsection will commence with what is known in this species.

  17. Unraveling incompatibility between wheat and the fungal pathogen Zymoseptoria tritici through apoplastic proteomics.

    Science.gov (United States)

    Yang, Fen; Li, Wanshun; Derbyshire, Mark; Larsen, Martin R; Rudd, Jason J; Palmisano, Giuseppe

    2015-05-08

    Hemibiotrophic fungal pathogen Zymoseptoria tritici causes severe foliar disease in wheat. However, current knowledge of molecular mechanisms involved in plant resistance to Z. tritici and Z. tritici virulence factors is far from being complete. The present work investigated the proteome of leaf apoplastic fluid with emphasis on both host wheat and Z. tritici during the compatible and incompatible interactions. The proteomics analysis revealed rapid host responses to the biotrophic growth, including enhanced carbohydrate metabolism, apoplastic defenses and stress, and cell wall reinforcement, might contribute to resistance. Compatibility between the host and the pathogen was associated with inactivated plant apoplastic responses as well as fungal defenses to oxidative stress and perturbation of plant cell wall during the initial biotrophic stage, followed by the strong induction of plant defenses during the necrotrophic stage. To study the role of anti-oxidative stress in Z. tritici pathogenicity in depth, a YAP1 transcription factor regulating antioxidant expression was deleted and showed the contribution to anti-oxidative stress in Z. tritici, but was not required for pathogenicity. This result suggests the functional redundancy of antioxidants in the fungus. The data demonstrate that incompatibility is probably resulted from the proteome-level activation of host apoplastic defenses as well as fungal incapability to adapt to stress and interfere with host cell at the biotrophic stage of the interaction.

  18. A nitrogen response pathway regulates virulence functions in Fusarium oxysporum via the protein kinase TOR and the bZIP protein MeaB.

    Science.gov (United States)

    López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

    2010-07-01

    During infection, fungal pathogens activate virulence mechanisms, such as host adhesion, penetration and invasive growth. In the vascular wilt fungus Fusarium oxysporum, the mitogen-activated protein kinase Fmk1 is required for plant infection and controls processes such as cellophane penetration, vegetative hyphal fusion, or root adhesion. Here, we show that these virulence-related functions are repressed by the preferred nitrogen source ammonium and restored by treatment with l-methionine sulfoximine or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR, respectively. Deletion of the bZIP protein MeaB also resulted in nitrogen source-independent activation of virulence mechanisms. Activation of these functions did not require the global nitrogen regulator AreA, suggesting that MeaB-mediated repression of virulence functions does not act through inhibition of AreA. Tomato plants (Solanum lycopersicum) supplied with ammonium rather than nitrate showed a significant reduction in vascular wilt symptoms when infected with the wild type but not with the DeltameaB strain. Nitrogen source also affected invasive growth in the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. We propose that a conserved nitrogen-responsive pathway might operate via TOR and MeaB to control virulence in plant pathogenic fungi.

  19. A Nitrogen Response Pathway Regulates Virulence Functions in Fusarium oxysporum via the Protein Kinase TOR and the bZIP Protein MeaB[C][W

    Science.gov (United States)

    López-Berges, Manuel S.; Rispail, Nicolas; Prados-Rosales, Rafael C.; Di Pietro, Antonio

    2010-01-01

    During infection, fungal pathogens activate virulence mechanisms, such as host adhesion, penetration and invasive growth. In the vascular wilt fungus Fusarium oxysporum, the mitogen-activated protein kinase Fmk1 is required for plant infection and controls processes such as cellophane penetration, vegetative hyphal fusion, or root adhesion. Here, we show that these virulence-related functions are repressed by the preferred nitrogen source ammonium and restored by treatment with l-methionine sulfoximine or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR, respectively. Deletion of the bZIP protein MeaB also resulted in nitrogen source–independent activation of virulence mechanisms. Activation of these functions did not require the global nitrogen regulator AreA, suggesting that MeaB-mediated repression of virulence functions does not act through inhibition of AreA. Tomato plants (Solanum lycopersicum) supplied with ammonium rather than nitrate showed a significant reduction in vascular wilt symptoms when infected with the wild type but not with the ΔmeaB strain. Nitrogen source also affected invasive growth in the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. We propose that a conserved nitrogen-responsive pathway might operate via TOR and MeaB to control virulence in plant pathogenic fungi. PMID:20639450

  20. Fungal infection in organ transplant patients.

    Science.gov (United States)

    Hong, Wei; Wen, Hai; Liao, Wanqing

    2003-09-01

    To review the characteristics and evolution of the fungal spectrum, and the risk factors causing fungal infection, and to make progress in diagnosing fungal infection after organ transplantation. An English-language literature search (MEDLINE 1990 - 2000) and bibliographic review of textbooks and review articles. Twenty-three articles were selected from the literature that specifically addressed the stated purpose. Fungal infections in organ transplant patients were generally divided into two types: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses; (2) opportunistic infection by fungal species that rarely cause invasive infection in normal hosts. The risk factors of fungal infection after a transplant can be evaluated and predicted according to the organ recipient's conditions before, during and after the transplant. Progress in early diagnostic methods during the past 10 years has mainly revolved around two aspects, culture and non-culture. It is important to undertake a systemic evaluation on the condition of the organ recipient before, during and after a transplant; should any risk factor for fungal infection be suspected, diagnosis should be made as early as possible by employing mycological techniques including culture and non-culture methods.

  1. Sample collection of virulent and non-virulent B. anthracis and Y. pestis for bioforensics analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hong-geller, Elizabeth [Los Alamos National Laboratory; Valdez, Yolanda E [Los Alamos National Laboratory; Shou, Yulin [Los Alamos National Laboratory; Yoshida, Thomas M [Los Alamos National Laboratory; Marrone, Babetta L [Los Alamos National Laboratory; Dunbar, John [Los Alamos National Laboratory

    2009-01-01

    Validated sample collection methods are needed for recovery of microbial evidence in the event of accidental or intentional release of biological agents into the environment. To address this need, we evaluated the sample recovery efficiencies of two collection methods -- swabs and wipes -- for both non-virulent and virulent strains of B. anthracis and Y. pestis from four types of non-porous surfaces: two hydrophilic surfaces, stainless steel and glass, and two hydrophobic surfaces, vinyl and plastic. Sample recovery was quantified using Real-time qPCR to assay for intact DNA signatures. We found no consistent difference in collection efficiency between swabs or wipes. Furthermore, collection efficiency was more surface-dependent for virulent strains than non-virulent strains. For the two non-virulent strains, B. anthracis Sterne and Y. pestis A1122, collection efficiency was approximately 100% and 1 %, respectively, from all four surfaces. In contrast, recovery of B. anthracis Ames spores and Y. pestis C092 from vinyl and plastic was generally lower compared to collection from glass or stainless steel, suggesting that surface hydrophobicity may playa role in the strength of pathogen adhesion. The surface-dependent collection efficiencies observed with the virulent strains may arise from strain-specific expression of capsular material or other cell surface receptors that alter cell adhesion to specific surfaces. These findings contribute to validation of standard bioforensics procedures and emphasize the importance of specific strain and surface interactions in pathogen detection.

  2. The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development.

    Science.gov (United States)

    Kumar, J P; Moses, K

    2001-07-01

    The onset of pattern formation in the developing Drosophila retina begins with the initiation of the morphogenetic furrow, the leading edge of a wave of retinal development that transforms a uniform epithelium, the eye imaginal disc into a near crystalline array of ommatidial elements. The initiation of this wave of morphogenesis is under the control of the secreted morphogens Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor Receptor and Notch signaling cascades are crucial components that are also required to initiate retinal development. We also show that the initiation of the morphogenetic furrow is the sum of two genetically separable processes: (1) the 'birth' of pattern formation at the posterior margin of the eye imaginal disc; and (2) the subsequent 'reincarnation' of retinal development across the epithelium.

  3. Differences in cell morphometry, cell wall topography and gp70 expression correlate with the virulence of Sporothrix brasiliensis clinical isolates.

    Directory of Open Access Journals (Sweden)

    Rafaela A Castro

    Full Text Available Sporotrichosis is a chronic infectious disease affecting both humans and animals. For many years, this subcutaneous mycosis had been attributed to a single etiological agent; however, it is now known that this taxon consists of a complex of at least four pathogenic species, including Sporothrix schenckii and Sporothrix brasiliensis. Gp70 was previously shown to be an important antigen and adhesin expressed on the fungal cell surface and may have a key role in immunomodulation and host response. The aim of this work was to study the virulence, morphometry, cell surface topology and gp70 expression of clinical isolates of S. brasiliensis compared with two reference strains of S. schenckii. Several clinical isolates related to severe human cases or associated with the Brazilian zoonotic outbreak of sporotrichosis were genotyped and clustered as S. brasiliensis. Interestingly, in a murine subcutaneous model of sporotrichosis, these isolates showed a higher virulence profile compared with S. schenckii. A single S. brasiliensis isolate from an HIV-positive patient not only showed lower virulence but also presented differences in cell morphometry, cell wall topography and abundant gp70 expression compared with the virulent isolates. In contrast, the highly virulent S. brasiliensis isolates showed reduced levels of cell wall gp70. These observations were confirmed by the topographical location of the gp70 antigen using immunoelectromicroscopy in both species. In addition, the gp70 molecule was sequenced and identified using mass spectrometry, and the sequenced peptides were aligned into predicted proteins using Blastp with the S. schenckii and S. brasiliensis genomes.

  4. Fungal colonization of air-conditioning systems

    Directory of Open Access Journals (Sweden)

    Ljaljević-Grbić Milica

    2008-01-01

    Full Text Available Fungi have been implicated as quantitatively the most important bioaerosol component of indoor air associated with contaminated air-conditioning systems. rarely, indoor fungi may cause human infections, but more commonly allergenic responses ranging from pneumonitis to asthma-like symptoms. From all air conditioner filters analyzed, 16 fungal taxa were isolated and identified. Aspergillus fumigatus causes more lethal infections worldwide than any other mold. Air-conditioning filters that adsorb moisture and volatile organics appear to provide suitable substrates for fungal colonization. It is important to stress that fungal colonization of air-conditioning systems should not be ignored, especially in hospital environments.

  5. Fungal infections in neutropenic cancer patients

    International Nuclear Information System (INIS)

    Parvez, T.

    2003-01-01

    Invasive fungal infections are important causes of morbidity and mortality in cancer patients with prolonged neutropenia following chemotherapy. Recent trends indicate a change toward infections by Aspergillus species, non-albicans species of Candida, and previously uncommon fungal pathogens. These have decreased susceptibility to current antifungal agents. In the last decade there has been much effort to find solutions for these changing trends. This article reviews current approaches to prevention and treatment of opportunistic fungal infections in postchemotherapy neutropenic patients and discussion future antifungal approaches and supportive methods. (author)

  6. Bone morphogenetic protein use in spine surgery-complications and outcomes: a systematic review.

    Science.gov (United States)

    Faundez, Antonio; Tournier, Clément; Garcia, Matthieu; Aunoble, Stéphane; Le Huec, Jean-Charles

    2016-06-01

    Because of significant complications related to the use of autologous bone grafts in spinal fusion surgery, bone substitutes and growth factors such as bone morphogenetic protein (BMP) have been developed. One of them, recombinant human (rh) BMP-2, has been approved by the Food and Drug Administration (FDA) for use under precise conditions. However, rhBMP-2-related side effects have been reported, used in FDA-approved procedures, but also in off-label use.A systematic review of clinical data was conducted to analyse the rhBMP-2-related adverse events (AEs), in order to assess their prevalence and the associated surgery practices. Medline search with keywords "bone morphogenetic protein 2", "lumbar spine", "anterolateral interbody fusion" (ALIF) and the filter "clinical trial". FDA published reports were also included. Study assessment was made by authors (experienced spine surgeons), based on quality of study designs and level of evidence. Extensive review of randomised controlled trials (RCTs) and controlled series published up to the present point, reveal no evidence of a significant increase of AEs related to rhBMP-2 use during ALIF surgeries, provided that it is used following FDA guidelines. Two additional RCTs performed with rhBMP-2 in combination with allogenic bone dowels reported increased bone remodelling in BMP-treated patients. This AE was transient and had no consequence on the clinical outcome of the patients. No other BMP-related AEs were reported in these studies. This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off

  7. Bone Morphogenetic Protein-Induced Msx1 and Msx2 Inhibit Myocardin-Dependent Smooth Muscle Gene Transcription▿

    OpenAIRE

    Hayashi, Ken'ichiro; Nakamura, Seiji; Nishida, Wataru; Sobue, Kenji

    2006-01-01

    During the onset and progression of atherosclerosis, the vascular smooth muscle cell (VSMC) phenotype changes from differentiated to dedifferentiated, and in some cases, this change is accompanied by osteogenic transition, resulting in vascular calcification. One characteristic of dedifferentiated VSMCs is the down-regulation of smooth muscle cell (SMC) marker gene expression. Bone morphogenetic proteins (BMPs), which are involved in the induction of osteogenic gene ex...

  8. The effect of mutation on Rhodococcus equi virulence plasmid gene expression and mouse virulence.

    Science.gov (United States)

    Ren, Jun; Prescott, John F

    2004-11-15

    An 81 kb virulence plasmid containing a pathogenicity island (PI) plays a crucial role in the pathogenesis of Rhodococcus equi pneumonia in foals but its specific function in virulence and regulation of plasmid-encoded virulence genes is unclear. Using a LacZ selection marker developed for R. equi in this study, in combination with an apramycin resistance gene, an efficient two-stage homologous recombination targeted gene mutation procedure was used to mutate three virulence plasmid genes, a LysR regulatory gene homologue (ORF4), a ResD-like two-component response regulator homologue (ORF8), and a gene (ORF10) of unknown function that is highly expressed by R. equi inside macrophages, as well as the chromosomal gene operon, phoPR. Virulence testing by liver clearance after intravenous injection in mice showed that the ORF4 and ORF8 mutants were fully attenuated, that the phoPR mutant was hypervirulent, and that virulence of the ORF10 mutant remained unchanged. A virulence plasmid DNA microarray was used to compare the plasmid gene expression profile of each of the four gene-targeted mutants against the parental R. equi strain. Changes were limited to PI genes and gene induction was observed for all mutants, suggesting that expression of virulence plasmid genes is dominated by a negative regulatory network. The finding of attenuation of ORF4 and ORF8 mutants despite enhanced transcription of vapA suggests that factors other than VapA are important for full expression of virulence. ORF1, a putative Lsr antigen gene, was strongly and similarly induced in all mutants, implying a common regulatory pathway affecting this gene for all four mutated genes. ORF8 is apparently the centre of this common pathway. Two distinct highly correlated gene induction patterns were observed, that of the ORF4 and ORF8 mutants, and that of the ORF10 and phoPR mutants. The gene induction pattern distinguishing these two groups paralleled their virulence in mice.

  9. Effects of Low Dose Chronic Radiation and Heavy Metals on Plants and Their Fungal and Virus Infections

    Directory of Open Access Journals (Sweden)

    A Dmitriev

    2009-06-01

    Full Text Available The effects of low dose chronic radiation on plant disease resistance and fungal and virus infections have been studied. The results obtained in the 10-km Chernobyl zone demonstrated a decrease in plant disease resistance and appearance of a "new" population of stem rust agents of cereal with a high frequency of more virulent clones. Radionuclide contamination and heavy metals lead to wider virus spread and a higher diversity of virus species. The Chernobyl zone is a territory of enhanced risk and potential threats for the environment. A special type of monitoring of microevolution processes in plant pathogens should provide better understanding of how serious these potential threats are.

  10. PNNL Fungal Biotechnology Core DOE-OBP Project

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Scott E.; Bruno, Kenneth S.; Butcher, Mark G.; Collett, James R.; Culley, David E.; Dai, Ziyu; Magnuson, Jon K.; Panisko, Ellen A.

    2009-11-30

    In 2009, we continued to address barriers to fungal fermentation in the primary areas of morphology control, genomics, proteomics, fungal hyperproductivity, biomass-to-products via fungal based consolidated bioprocesses, and filamentous fungal ethanol. “Alternative renewable fuels from fungi” was added as a new subtask. Plans were also made to launch a new advanced strain development subtask in FY2010.

  11. The Hos2 Histone Deacetylase Controls Ustilago maydis Virulence through Direct Regulation of Mating-Type Genes.

    Directory of Open Access Journals (Sweden)

    Alberto Elías-Villalobos

    2015-08-01

    Full Text Available Morphological changes are critical for host colonisation in plant pathogenic fungi. These changes occur at specific stages of their pathogenic cycle in response to environmental signals and are mediated by transcription factors, which act as master regulators. Histone deacetylases (HDACs play crucial roles in regulating gene expression, for example by locally modulating the accessibility of chromatin to transcriptional regulators. It has been reported that HDACs play important roles in the virulence of plant fungi. However, the specific environment-sensing pathways that control fungal virulence via HDACs remain poorly characterised. Here we address this question using the maize pathogen Ustilago maydis. We find that the HDAC Hos2 is required for the dimorphic switch and pathogenic development in U. maydis. The deletion of hos2 abolishes the cAMP-dependent expression of mating type genes. Moreover, ChIP experiments detect Hos2 binding to the gene bodies of mating-type genes, which increases in proportion to their expression level following cAMP addition. These observations suggest that Hos2 acts as a downstream component of the cAMP-PKA pathway to control the expression of mating-type genes. Interestingly, we found that Clr3, another HDAC present in U. maydis, also contributes to the cAMP-dependent regulation of mating-type gene expression, demonstrating that Hos2 is not the only HDAC involved in this control system. Overall, our results provide new insights into the role of HDACs in fungal phytopathogenesis.

  12. HIV/AIDS and Fungal Infections

    Science.gov (United States)

    ... Environmental Diseases Mycotic Diseases Branch People living with HIV/AIDS Recommend on Facebook Tweet Share Compartir As ... Page Preventing fungal infections in people living with HIV/AIDS Fungi are difficult to avoid because they ...

  13. Postharvest fungal deterioration of tomato ( Lycopersicum ...

    African Journals Online (AJOL)

    Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives ... tomatoes and pepper were sourced from Mile 12 Market in Lagos state. ... the ingestion of mycotoxins that are usually associated with fungal species), ...

  14. Fungal rhino sinusitisin in tehran, iran

    NARCIS (Netherlands)

    Nazeri, M.; Hashemi, S.J.; Ardehali, M.; Rezaei, S.; Seyedmousavi, S.; Zareei, M.; Hosseinjani, E.

    2015-01-01

    BACKGROUND: Fungal rhino sinusitis (FRS) is an important infection of para nasal sinuses, which encompasses two main categories; invasive and noninvasive forms according to histopathological findings. Aspergillus spp are the most common species isolated from noninvasive form, while Mucorales are

  15. Zoosporic fungal parasites of marine biota

    Digital Repository Service at National Institute of Oceanography (India)

    RaghuKumar, C.

    laboratory media. In such instances, a detailed and careful examination of the disease symptoms and the endobiotic fungal parasites is to be recorded. Maintaining dual culture of the healthy and infected host also helps to fulfill these postulates partially....

  16. Organ Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... are mild skin rashes, but others can be deadly, like fungal pneumonia. Because of this, it’s important ... the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on ...

  17. Air Contamination With Fungals In Museum

    Science.gov (United States)

    Scarlat, Iuliana; Haiducu, Maria; Stepa, Raluca

    2015-07-01

    The aim of the studies was to determine the level and kind of fungal contamination of air in museum, deposits patrimony, restoration and conservation laboratories and their effects on health of workers. Microbiological air purity was measured with a SAS-100 Surface Air System impactor. The fungal contamination was observed in all 54 rooms where we made determinations. The highest levels of fungal were recorded at rooms with hygroscopic patrimony objects, eg carpets, chairs, upholstered chairs, books etc. The most species identified included under common allergens: Aspergillus, Penicillium, and Mucor. There fungal species belonging to the genus identified in this study, can trigger serious diseases museum workers, such as for example Aspergillus fumigatus, known allergies and toxic effects that may occur. In some places of the museum, occupational exposure limit values to fungi present in the air in the work environment, recommended by the specialized literature, have been overcome.

  18. Fungal keratitis - improving diagnostics by confocal microscopy

    DEFF Research Database (Denmark)

    Nielsen, Esben; Heegaard, S; Prause, J U

    2013-01-01

    Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological...... analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience...... with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12...

  19. Effective Inhibition of Bone Morphogenetic Protein Function by Highly Specific Llama-Derived Antibodies.

    Science.gov (United States)

    Calpe, Silvia; Wagner, Koen; El Khattabi, Mohamed; Rutten, Lucy; Zimberlin, Cheryl; Dolk, Edward; Verrips, C Theo; Medema, Jan Paul; Spits, Hergen; Krishnadath, Kausilia K

    2015-11-01

    Bone morphogenetic proteins (BMP) have important but distinct roles in tissue homeostasis and disease, including carcinogenesis and tumor progression. A large number of BMP inhibitors are available to study BMP function; however, as most of these antagonists are promiscuous, evaluating specific effects of individual BMPs is not feasible. Because the oncogenic role of the different BMPs varies for each neoplasm, highly selective BMP inhibitors are required. Here, we describe the generation of three types of llama-derived heavy chain variable domains (VHH) that selectively bind to either BMP4, to BMP2 and 4, or to BMP2, 4, 5, and 6. These generated VHHs have high affinity to their targets and are able to inhibit BMP signaling. Epitope binning and docking modeling have shed light into the basis for their BMP specificity. As opposed to the wide structural reach of natural inhibitors, these small molecules target the grooves and pockets of BMPs involved in receptor binding. In organoid experiments, specific inhibition of BMP4 does not affect the activation of normal stem cells. Furthermore, in vitro inhibition of cancer-derived BMP4 noncanonical signals results in an increase of chemosensitivity in a colorectal cancer cell line. Therefore, because of their high specificity and low off-target effects, these VHHs could represent a therapeutic alternative for BMP4(+) malignancies. ©2015 American Association for Cancer Research.

  20. Expression of bone morphogenetic proteins and Msx genes during root formation.

    Science.gov (United States)

    Yamashiro, T; Tummers, M; Thesleff, I

    2003-03-01

    Like crown development, root formation is also regulated by interactions between epithelial and mesenchymml tissues. Bone morphogenetic proteins (BMPs), together with the transcription factors Msx1 and Msx2, play important roles in these interactions during early tooth morphogenesis. To investigate the involvement of this signaling pathway in root development, we analyzed the expression patterns of Bmp2, Bmp3, Bmp4, and Bmp7 as well as Msx1 and Msx2 in the roots of mouse molars. Bmp4 was expressed in the apical mesenchyme and Msx2 in the root sheath. However, Bmps were not detected in the root sheath epithelium, and Msx transcripts were absent from the underlying mesenchyme. These findings indicate that this Bmp signaling pathway, required for tooth initiation, does not regulate root development, but we suggest that root shape may be regulated by a mechanism similar to that regulating crown shape in cap-stage tooth germs. Msx2 expression continued in the epithelial cell rests of Malassez, and the nearby cementoblasts intensely expressed Bmp3, which may regulate some functions of the fragmented epithelium.

  1. Morphogenetic, structural and productive traits of buffel grass under different irrigation regimes

    Directory of Open Access Journals (Sweden)

    Maria Janiele Ferreira Coutinho

    2015-06-01

    Full Text Available The water restriction conditions in the Brazilian semiarid region are one of the most limiting factors to the establishment and yield of forage grasses. This study aimed to evaluate the effect of different irrigation regimes on morphogenetic, structural and productive traits of buffel grass. Arandomized blocks design, with five treatments and six replications, was used. Treatments consisted of five irrigation regimes, corresponding to the intervals of 2, 4, 6, 8 and 10 days. The traits analyzed were: leaf emergence rate, phyllochron, leaf and stem elongation rate, leaf senescence rate, final leaf length, number of green leaves per tiller, number of tillers, stem height, leaf/stem ratio, leaf area index, dry mass of green leaf and stem, dry mass of green, dead and total forage, root dry mass, dry mass and green dry mass/dead dry mass ratio. The final leaf length and dead forage dry mass were not affected by the irrigation regimes. The leaf/stem ratio followed a quadratic model, maintaining the value of 0.51 up to the irrigation regime of four days. The other morphological, structural and productive traits decreased linearly with increasing irrigation frequencies. The irrigation intervals promoted reductions in the morphological, structural and productive parameters of buffel grass, when grown under greenhouse conditions. The irrigation regime of 2 days stands out as the least restrictive to the development of buffel grass.

  2. Purification of bone morphogenetic protein-2 from refolding mixtures using mixed-mode membrane chromatography.

    Science.gov (United States)

    Gieseler, Gesa; Pepelanova, Iliyana; Stuckenberg, Lena; Villain, Louis; Nölle, Volker; Odenthal, Uwe; Beutel, Sascha; Rinas, Ursula; Scheper, Thomas

    2017-01-01

    In this study, we present the development of a process for the purification of recombinant human bone morphogenetic protein-2 (rhBMP-2) using mixed-mode membrane chromatography. RhBMP-2 was produced as inclusion bodies in Escherichia coli. In vitro refolding using rapid dilution was carried out according to a previously established protocol. Different membrane chromatography phases were analyzed for their ability to purify BMP-2. A membrane phase with salt-tolerant properties resulting from mixed-mode ligand chemistry was able to selectively purify BMP-2 dimer from refolding mixtures. No further purification or polishing steps were necessary and high product purity was obtained. The produced BMP-2 exhibited a biological activity of 7.4 × 10 5  U/mg, comparable to commercial preparations. Mixed-mode membrane chromatography can be a valuable tool for the direct purification of proteins from solutions with high-conductivity, for example refolding buffers. In addition, in this particular case, it allowed us to circumvent the use of heparin-affinity chromatography, thus allowing the design of an animal-component-free process.

  3. Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition.

    Science.gov (United States)

    Meyers, Emily A; Gobeske, Kevin T; Bond, Allison M; Jarrett, Jennifer C; Peng, Chian-Yu; Kessler, John A

    2016-02-01

    Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors

    International Nuclear Information System (INIS)

    Kalen, Anders; Wahlstroem, Ola; Linder, Cecilia Halling; Magnusson, Per

    2008-01-01

    Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation

  5. A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

    Directory of Open Access Journals (Sweden)

    Thanyaphoo Suphannee

    2016-09-01

    Full Text Available Silicon-substituted calcium phosphate (Si-CaP was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2 was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

  6. Polyhedral microcrystals encapsulating bone morphogenetic protein 2 improve healing in the alveolar ridge.

    Science.gov (United States)

    Matsumoto, Goichi; Ueda, Takayo; Sugita, Yoshihiko; Kubo, Katsutoshi; Mizoguchi, Megumi; Kotani, Eiji; Oda, Naoki; Kawamata, Shin; Segami, Natsuki; Mori, Hajime

    2015-08-01

    Atelocollagen sponges incorporating polyhedra encapsulating bone morphogenetic protein 2 (BMP-2) were implanted into lateral bone defects in the mandible. Half of the bone defects on the left side were treated with atelocollagen sponges containing 1.8 × 10(7) BMP-2 polyhedra, and half were treated with sponges containing 3.6 × 10(6) BMP-2 polyhedra. As controls, we treated the right-side bone defects in each animal with an atelocollagen sponge containing 5 µg of recombinant human BMP-2 (rhBMP-2) or 1.8 × 10(7) empty polyhedral. After a healing period of six months, whole mandibles were removed for micro-computed tomography (CT) and histological analyses. Micro-CT images showed that more bone had formed at all experimental sites than at control sites. However, the density of the new bone was not significantly higher at sites with an atelocollagen sponge containing BMP-2 polyhedra than at sites with an atelocollagen sponge containing rhBMP-2 or empty polyhedra. Histological examination confirmed that the BMP-2 polyhedra almost entirely replaced the atelocollagen sponges and connected the original bone with the regenerated bone. These results show that the BMP-2 delivery system facilitates the regeneration of new bone in the mandibular alveolar bone ridge and has an advance in the technology of bone regeneration for implant site development. © The Author(s) 2015.

  7. Morphogenetic mechanisms of coelom formation in the direct-developing sea urchin Heliocidaris erythrogramma.

    Science.gov (United States)

    Smith, Margaret S; Collins, Steve; Raff, Rudolf A

    2009-01-01

    Indirect development via a feeding pluteus larva represents the ancestral mode of sea urchin development. However, some sea urchin species exhibit a derived form of development, called direct development, in which features of the feeding larva are replaced by accelerated development of the adult. A major difference between these two developmental modes is the timing of the formation of the left coelom and initiation of adult development. These processes occur much earlier in developmental and absolute time in direct developers and may be underlain by changes in morphogenetic processes. In this study, we explore whether differences in the cellular mechanisms responsible for the development of the left coelom and adult structures are associated with the change in the timing of their formation in the direct-developing sea urchin Heliocidaris erythrogramma. We present evidence that left coelom formation in H. erythrogramma, which differs in major aspects of coelom formation in indirect developers, is not a result of cell division. Further, we demonstrate that subsequent development of adult structures requires cell division.

  8. Exaggerated inflammatory response after use of recombinant bone morphogenetic protein in recurrent unicameral bone cysts.

    Science.gov (United States)

    MacDonald, Kevin M; Swanstrom, Morgan M; McCarthy, James J; Nemeth, Blaise A; Guliani, Teresa A; Noonan, Kenneth J

    2010-03-01

    Recurrent unicameral bone cysts (UBCs) can result in significant morbidity during a child's physical and emotional development. Multiple treatment options are available and a review of the literature fails to clearly define the optimal treatment for UBCs. Recombinant bone morphogenetic protein (BMP) has been used with success in other disorders of poor bone formation. This manuscript is the first to report on the use of recombinant BMP in the treatment of UBCs. Three patients with recurrent UBCs underwent revision surgery with recombinant BMP. Radiographic and medical review was performed and is reported here. In these patients, the use of BMP failed to fully resolve their UBC; 2 patients had complete recurrence that required further surgery. In addition to poor radiographic results, all patients developed exaggerated inflammatory responses in the acute postoperative period. Each child developed clinically significant limb swelling and pain that mimicked infection. On the basis of our poor radiographic results and a paradoxical clinical result, we no longer recommend the use of recombinant BMP in the manner reported here for the treatment of recurrent UBCs. Level IV, case series.

  9. Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation of Integrin and Bone Morphogenetic Protein Pathways.

    Science.gov (United States)

    Lee, Yoo-Mi; Yun, Hyung-Mun; Lee, Hye-Young; Lim, Hyun-Chang; Lee, Hae-Hyoung; Kim, Hae-Won; Kim, Eun-Cheol

    2017-02-01

    A xerogel was interfaced onto biopolymer nanofibers though a core–shell electrospinning design for bone regeneration. The xerogel-interfaced biopolymer nanofibrous matrix was bioactive and highly hydrophilic, with a significant decrease in the water contact angle. The matrix showed excellent in vitro responses of primary osteoblasts in terms of adhesion, proliferation, and migration. Furthermore, the osteoblastic differentiation of cells, including alkaline phosphatase activity, mineralization, and gene expression, was significantly upregulated by the xerogel interface. In vivo animal tests in a critical-sized calvarial defect confirmed the new bone formation ability of the xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the stimulation were implied to be integrin and bone morphogenetic protein (BMP) pathways, as demonstrated by the activation of integrin (α2β1) and downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-κB), as well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be a promising scaffold candidate for bone regeneration.

  10. Regulation of Oligodendrocyte Progenitor Cell Maturation by PPARδ: Effects on Bone Morphogenetic Proteins

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Simonini

    2009-12-01

    Full Text Available In EAE (experimental autoimmune encephalomyelitis, agonists of PPARs (peroxisome proliferator-activated receptors provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells, and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins. We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ-null mice. In OPCs derived from E13 mice (where E is embryonic day, GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ-null compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

  11. Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma

    International Nuclear Information System (INIS)

    Cui, Ximao; Yang, Yili; Jia, Deshui; Jing, Ying; Zhang, Shouhua; Zheng, Shan; Cui, Long; Dong, Rui; Dong, Kuiran

    2017-01-01

    Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB. - Highlights: • BMPR2 expression was downregulated in primary NB and was more signifcant in high grade NB. • BMPR2 expression was accompanied by the decrease of NB markers ferritin and enolase. • Enforced expression of BMPR2 decreased proliferation and colony formation ability of cultured NB cells. • Knockdown of BMPR2 led to increased cell growth, clonality and tumorigenicity in mice. • Patients with NB expressing higher level of BMPR2 had significant better overall survival than those with low level.

  12. Morphogenetic and structural characteristics of guinea grass tillers at different ages under intermittent stocking

    Directory of Open Access Journals (Sweden)

    Rodrigo Amorim Barbosa

    2012-07-01

    Full Text Available The objective of this research was to assess morphogenetic and structural characteristics of tillers of guinea grass cv. Tanzania at different ages. The pastures of guinea grass were managed in six pasture conditions related to the combination of three frequencies (90, 95, and 99% light interception and two post-grazing heights (25 and 50 cm. In these six pastures conditions, three tiller ages were evaluated (young, mature, and old. The design was of completely randomized block with three replications. Young tillers exhibited higher leaf appearance rate and leaf elongation rate and, consequently, higher final leaf length and number of live leaves than mature and old tillers, regardless of the pasture condition. On pastures managed with 90 or 95% light interception associated with a post-grazing height of 25 cm, old tillers presented longer leaf lifespan than young and mature ones. There is a progressive reduction in the vigor of growth of pastures of guinea grass cv. Tanzania with advancing tiller age.

  13. Label-Free Quantitative Proteomic Analysis of Puccinia psidii Uredospores Reveals Differences of Fungal Populations Infecting Eucalyptus and Guava.

    Science.gov (United States)

    Quecine, Maria Carolina; Leite, Thiago Falda; Bini, Andressa Peres; Regiani, Thais; Franceschini, Lívia Maria; Budzinski, Ilara Gabriela Frasson; Marques, Felipe Garbelini; Labate, Mônica Teresa Veneziano; Guidetti-Gonzalez, Simone; Moon, David Henry; Labate, Carlos Alberto

    2016-01-01

    Puccinia psidii sensu lato (s.l.) is the causal agent of eucalyptus and guava rust, but it also attacks a wide range of plant species from the myrtle family, resulting in a significant genetic and physiological variability among populations accessed from different hosts. The uredospores are crucial to P. psidii dissemination in the field. Although they are important for the fungal pathogenesis, their molecular characterization has been poorly studied. In this work, we report the first in-depth proteomic analysis of P. psidii s.l. uredospores from two contrasting populations: guava fruits (PpGuava) and eucalyptus leaves (PpEucalyptus). NanoUPLC-MSE was used to generate peptide spectra that were matched to the UniProt Puccinia genera sequences (UniProt database) resulting in the first proteomic analysis of the phytopathogenic fungus P. psidii. Three hundred and fourty proteins were detected and quantified using Label free proteomics. A significant number of unique proteins were found for each sample, others were significantly more or less abundant, according to the fungal populations. In PpGuava population, many proteins correlated with fungal virulence, such as malate dehydrogenase, proteossomes subunits, enolases and others were increased. On the other hand, PpEucalyptus proteins involved in biogenesis, protein folding and translocation were increased, supporting the physiological variability of the fungal populations according to their protein reservoirs and specific host interaction strategies.

  14. Phylogenetic analysis of fungal heterotrimeric G protein-encoding genes and their expression during dimorphism in Mucor circinelloides.

    Science.gov (United States)

    Valle-Maldonado, Marco Iván; Jácome-Galarza, Irvin Eduardo; Díaz-Pérez, Alma Laura; Martínez-Cadena, Guadalupe; Campos-García, Jesús; Ramírez-Díaz, Martha Isela; Reyes-De la Cruz, Homero; Riveros-Rosas, Héctor; Díaz-Pérez, César; Meza-Carmen, Víctor

    2015-12-01

    In fungi, heterotrimeric G proteins are key regulators of biological processes such as mating, virulence, morphology, among others. Mucor circinelloides is a model organism for many biological processes, and its genome contains the largest known repertoire of genes that encode putative heterotrimeric G protein subunits in the fungal kingdom: twelve Gα (McGpa1-12), three Gβ (McGpb1-3), and three Gγ (McGpg1-3). Phylogenetic analysis of fungal Gα showed that they are divided into four distinct groups as reported previously. Fungal Gβ and Gγ are also divided into four phylogenetic groups, and to our understanding this is the first report of a phylogenetic classification for fungal Gβ and Gγ subunits. Almost all genes that encode putative heterotrimeric G subunits in M. circinelloides are differentially expressed during dimorphic growth, except for McGpg1 (Gγ) that showed very low mRNA levels at all developmental stages. Moreover, several of the subunits are expressed in a similar pattern and at the same level, suggesting that they constitute discrete complexes. For example, McGpb3 (Gβ), and McGpg2 (Gγ), are co-expressed during mycelium growth, and McGpa1, McGpb2, and McGpg2, are co-expressed during yeast development. These findings provide the conceptual framework to study the biological role of these genes during M. circinelloides morphogenesis. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  15. Label-Free Quantitative Proteomic Analysis of Puccinia psidii Uredospores Reveals Differences of Fungal Populations Infecting Eucalyptus and Guava.

    Directory of Open Access Journals (Sweden)

    Maria Carolina Quecine

    Full Text Available Puccinia psidii sensu lato (s.l. is the causal agent of eucalyptus and guava rust, but it also attacks a wide range of plant species from the myrtle family, resulting in a significant genetic and physiological variability among populations accessed from different hosts. The uredospores are crucial to P. psidii dissemination in the field. Although they are important for the fungal pathogenesis, their molecular characterization has been poorly studied. In this work, we report the first in-depth proteomic analysis of P. psidii s.l. uredospores from two contrasting populations: guava fruits (PpGuava and eucalyptus leaves (PpEucalyptus. NanoUPLC-MSE was used to generate peptide spectra that were matched to the UniProt Puccinia genera sequences (UniProt database resulting in the first proteomic analysis of the phytopathogenic fungus P. psidii. Three hundred and fourty proteins were detected and quantified using Label free proteomics. A significant number of unique proteins were found for each sample, others were significantly more or less abundant, according to the fungal populations. In PpGuava population, many proteins correlated with fungal virulence, such as malate dehydrogenase, proteossomes subunits, enolases and others were increased. On the other hand, PpEucalyptus proteins involved in biogenesis, protein folding and translocation were increased, supporting the physiological variability of the fungal populations according to their protein reservoirs and specific host interaction strategies.

  16. Human Fungal Pathogens of Mucorales and Entomophthorales.

    Science.gov (United States)

    Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S; Voigt, Kerstin; Lee, Soo Chan

    2014-11-06

    In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term "zygomycosis" is often used as a synonym for "mucormycosis." In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are monophyletic. Thus, the term "zygomycosis" needed to be further specified, resulting in the terms "mucormycosis" and "entomophthoramycosis." This review covers these two different types of fungal infections. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Botrytis cinerea protein O-mannosyltransferases play critical roles in morphogenesis, growth, and virulence.

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    Mario González

    Full Text Available Protein O-glycosylation is crucial in determining the structure and function of numerous secreted and membrane-bound proteins. In fungi, this process begins with the addition of a mannose residue by protein O-mannosyltransferases (PMTs in the lumen side of the ER membrane. We have generated mutants of the three Botrytis cinerea pmt genes to study their role in the virulence of this wide-range plant pathogen. B. cinerea PMTs, especially PMT2, are critical for the stability of the cell wall and are necessary for sporulation and for the generation of the extracellular matrix. PMTs are also individually required for full virulence in a variety of hosts, with a special role in the penetration of intact plant leaves. The most significant case is that of grapevine leaves, whose penetration requires the three functional PMTs. Furthermore, PMT2 also contributes significantly to fungal adherence on grapevine and tobacco leaves. Analysis of extracellular and membrane proteins showed significant changes in the pattern of protein secretion and glycosylation by the pmt mutants, and allowed the identification of new protein substrates putatively glycosylated by specific PMTs. Since plants do no possess these enzymes, PMTs constitute a promising target in the development of novel control strategies against B. cinerea.

  18. Entomopathogenic fungi as biological controllers: New insights into their virulence and pathogenicity

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    Shahid Ali Ahmad

    2012-01-01

    Full Text Available Entomopathogenic fungi vary considerably in their mode of action and virulence. Successful infection depends primarily on the adherence and penetration ability of a fungus to the host integuments. A variety of extracellular enzymes is produced during the degradation of insect integument. The attempts to control insects have changed over time from chemicals to natural control methods. This is why the development of natural methods of insect control or biopesticides, is preferred. By the use of fungal entomopathogens, insect pests can be controlled. There is no doubt that insects have been used for many years, but their effective use in the field remains elusive. However, their additional role in nature has also been discovered. Comparison of entomopathogens with conventional chemical pesticides depends on their efficiency and cost. In addition to efficiency, there are advantages in using microbial control agents, such as human safety and other non-target organisms; pesticide residues are minimized in food and biodiversity increased in managed ecosystems. In the present review the pathogenicity and virulence of entomopathogenic fungi and their role as biological control agents using biotechnology will be discussed.

  19. Biological roles of fungal carotenoids.

    Science.gov (United States)

    Avalos, Javier; Carmen Limón, M

    2015-08-01

    Carotenoids are terpenoid pigments widespread in nature, produced by bacteria, fungi, algae and plants. They are also found in animals, which usually obtain them through the diet. Carotenoids in plants provide striking yellow, orange or red colors to fruits and flowers, and play important metabolic and physiological functions, especially relevant in photosynthesis. Their functions are less clear in non-photosynthetic microorganisms. Different fungi produce diverse carotenoids, but the mutants unable to produce them do not exhibit phenotypic alterations in the laboratory, apart of lack of pigmentation. This review summarizes the current knowledge on the functional basis for carotenoid production in fungi. Different lines of evidence support a protective role of carotenoids against oxidative stress and exposure to visible light or UV irradiation. In addition, the carotenoids are intermediary products in the biosynthesis of physiologically active apocarotenoids or derived compounds. This is the case of retinal, obtained from the symmetrical oxidative cleavage of β-carotene. Retinal is the light-absorbing prosthetic group of the rhodopsins, membrane-bound photoreceptors present also in many fungal species. In Mucorales, β-carotene is an intermediary in the synthesis of trisporoids, apocarotenoid derivatives that include the sexual hormones the trisporic acids, and they are also presumably used in the synthesis of sporopollenin polymers. In conclusion, fungi have adapted their ability to produce carotenoids for different non-essential functions, related with stress tolerance or with the synthesis of physiologically active by-products.

  20. Burden of fungal infections in Senegal.

    Science.gov (United States)

    Badiane, Aida S; Ndiaye, Daouda; Denning, David W

    2015-10-01

    Senegal has a high rate of tuberculosis and a low HIV seropositivity rate and aspergilloma, life-threatening fungal infections, dermatophytosis and mycetoma have been reported in this study. All published epidemiology papers reporting fungal infection rates from Senegal were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in each to estimate national incidence or prevalence. The results show that tinea capitis is common being found in 25% of children, ~1.5 million. About 191,000 Senegalese women get recurrent vaginal thrush, ≥4 times annually. We estimate 685 incident cases of chronic pulmonary aspergillosis (CPA) following TB and prevalence of 2160 cases. Asthma prevalence in adults varies from 3.2% to 8.2% (mean 5%); 9976 adults have allergic bronchopulmonary aspergillosis (ABPA) and 13,168 have severe asthma with fungal sensitisation (SAFS). Of the 59,000 estimated HIV-positive patients, 366 develop cryptococcal meningitis; 1149 develop Pneumocystis pneumonia and 1946 develop oesophageal candidiasis, in which oral candidiasis (53%) and dermatophytosis (16%) are common. Since 2008-2010, 113 cases of mycetoma were diagnosed. In conclusion, we estimate that 1,743,507 (12.5%) people in Senegal suffer from a fungal infection, excluding oral candidiasis, fungal keratitis, invasive candidiasis or aspergillosis. Diagnostic and treatment deficiencies should be rectified to allow epidemiological studies. © 2015 Blackwell Verlag GmbH.

  1. Copper tolerance and virulence in bacteria

    Science.gov (United States)

    Ladomersky, Erik; Petris, Michael J.

    2015-01-01

    Copper (Cu) is an essential trace element for all aerobic organisms. It functions as a cofactor in enzymes that catalyze a wide variety of redox reactions due to its ability to cycle between two oxidation states, Cu(I) and Cu(II). This same redox property of copper has the potential to cause toxicity if copper homeostasis is not maintained. Studies suggest that the toxic properties of copper are harnessed by the innate immune system of the host to kill bacteria. To counter such defenses, bacteria rely on copper tolerance genes for virulence within the host. These discoveries suggest bacterial copper intoxication is a component of host nutritional immunity, thus expanding our knowledge of the roles of copper in biology. This review summarizes our current understanding of copper tolerance in bacteria, and the extent to which these pathways contribute to bacterial virulence within the host. PMID:25652326

  2. Riboregulators: Fine-Tuning Virulence in Shigella.

    Science.gov (United States)

    Fris, Megan E; Murphy, Erin R

    2016-01-01

    Within the past several years, RNA-mediated regulation (ribo-regulation) has become increasingly recognized for its importance in controlling critical bacterial processes. Regulatory RNA molecules, or riboregulators, are perpetually responsive to changes within the micro-environment of a bacterium. Notably, several characterized riboregulators control virulence in pathogenic bacteria, as is the case for each riboregulator characterized to date in Shigella. The timing of virulence gene expression and the ability of the pathogen to adapt to rapidly changing environmental conditions is critical to the establishment and progression of infection by Shigella species; ribo-regulators mediate each of these important processes. This mini review will present the current state of knowledge regarding RNA-mediated regulation in Shigella by detailing the characterization and function of each identified riboregulator in these pathogens.

  3. Transposable elements as stress adaptive capacitors induce genomic instability in fungal pathogen Magnaporthe oryzae.

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    Sonia Chadha

    Full Text Available A fundamental problem in fungal pathogenesis is to elucidate the evolutionary forces responsible for genomic rearrangements leading to races with fitter genotypes. Understanding the adaptive evolutionary mechanisms requires identification of genomic components and environmental factors reshaping the genome of fungal pathogens to adapt. Herein, Magnaporthe oryzae, a model fungal plant pathogen is used to demonstrate the impact of environmental cues on transposable elements (TE based genome dynamics. For heat shock and copper stress exposed samples, eight TEs belonging to class I and II family were employed to obtain DNA profiles. Stress induced mutant bands showed a positive correlation with dose/duration of stress and provided evidences of TEs role in stress adaptiveness. Further, we demonstrate that genome dynamics differ for the type/family of TEs upon stress exposition and previous reports of stress induced MAGGY transposition has underestimated the role of TEs in M. oryzae. Here, we identified Pyret, MAGGY, Pot3, MINE, Mg-SINE, Grasshopper and MGLR3 as contributors of high genomic instability in M. oryzae in respective order. Sequencing of mutated bands led to the identification of LTR-retrotransposon sequences within regulatory regions of psuedogenes. DNA transposon Pot3 was identified in the coding regions of chromatin remodelling protein containing tyrosinase copper-binding and PWWP domains. LTR-retrotransposons Pyret and MAGGY are identified as key components responsible for the high genomic instability and perhaps these TEs are utilized by M. oryzae for its acclimatization to adverse environmental conditions. Our results demonstrate how common field stresses change genome dynamics of pathogen and provide perspective to explore the role of TEs in genome adaptability, signalling network and its impact on the virulence of fungal pathogens.

  4. Virulence Factors of Erwinia amylovora: A Review

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    Núria Piqué

    2015-06-01

    Full Text Available Erwinia amylovora, a Gram negative bacteria of the Enterobacteriaceae family, is the causal agent of fire blight, a devastating plant disease affecting a wide range of host species within Rosaceae and a major global threat to commercial apple and pear production. Among the limited number of control options currently available, prophylactic application of antibiotics during the bloom period appears the most effective. Pathogen cells enter plants through the nectarthodes of flowers and other natural openings, such as wounds, and are capable of rapid movement within plants and the establishment of systemic infections. Many virulence determinants of E. amylovora have been characterized, including the Type III secretion system (T3SS, the exopolysaccharide (EPS amylovoran, biofilm formation, and motility. To successfully establish an infection, E. amylovora uses a complex regulatory network to sense the relevant environmental signals and coordinate the expression of early and late stage virulence factors involving two component signal transduction systems, bis-(3′-5′-cyclic di-GMP (c-di-GMP and quorum sensing. The LPS biosynthetic gene cluster is one of the relatively few genetic differences observed between Rubus- and Spiraeoideae-infecting genotypes of E. amylovora. Other differential factors, such as the presence and composition of an integrative conjugative element associated with the Hrp T3SS (hrp genes encoding the T3SS apparatus, have been recently described. In the present review, we present the recent findings on virulence factors research, focusing on their role in bacterial pathogenesis and indicating other virulence factors that deserve future research to characterize them.

  5. The C-terminal MIR-containing region in the Pmt1 O-mannosyltransferase restrains sporulation and is dispensable for virulence in Beauveria bassiana.

    Science.gov (United States)

    He, Zhangjiang; Luo, Linli; Keyhani, Nemat O; Yu, Xiaodong; Ying, Shenghua; Zhang, Yongjun

    2017-02-01

    Protein O-mannosyltransferases (Pmts) belong to a highly conserved protein family responsible for the initiation of O-glycosylation of many proteins. Pmts contain one dolichyl-phosphate-mannose-protein mannosyltransferases (PMT) domain and three MIR motifs (mannosyltransferase, inositol triphosphate, and ryanodine receptor) that are essential for activity in yeast. We report that in the insect fungal pathogen, Beauveria bassiana, deletion of the C-terminal Pmt1 MIR-containing region (Pmt1∆ 311-902 ) does not alter O-mannosyltransferase activity, but does increase total cell wall protein O-mannosylation levels and results in phenotypic changes in fungal development and cell wall stability. B. bassiana mutants harboring the Pmt1 ∆ 311-902 mutation displayed a significant increase in conidiation with up-regulation of conidiation-associated genes and an increase in biomass accumulation as compared to the wild-type parent. However, decreased vegetative growth and blastospore production was noted, and Pmt1 ∆ 311-902 mutants were altered in cell wall composition and cell surface features. Insect bioassays revealed little effect on virulence for the Pmt1 ∆ 311-902 strain via cuticle infection or intrahemocoel injection assays, although differences in hyphal body differentiation in the host hemolymph and up-regulation of virulence-associated genes were noted. These data suggest novel roles for Pmt1 in negatively regulating conidiation and demonstrate that the C-terminal Pmt1 MIR-containing region is dispensable for enzymatic activity and organismal virulence.

  6. The Aspergillus fumigatus Sialidase (Kdnase Contributes to Cell Wall Integrity and Virulence in Amphotericin B-Treated Mice

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    Jason R. Nesbitt

    2018-01-01

    Full Text Available Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening invasive pulmonary aspergillosis (IPA in immunocompromised individuals. We previously characterized an exo-sialidase from A. fumigatus that prefers the sialic acid substrate, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (Kdn; hence it is a Kdnase. Sialidases are known virulence factors in other pathogens; therefore, the goal of our study was to evaluate the importance of Kdnase in A. fumigatus. A kdnase knockout strain (Δkdnase was unable to grow on medium containing Kdn and displayed reduced growth and abnormal morphology. Δkdnase was more sensitive than wild type to hyperosmotic conditions and the antifungal agent, amphotericin B. In contrast, Δkdnase had increased resistance to nikkomycin, Congo Red and Calcofluor White indicating activation of compensatory cell wall chitin deposition. Increased cell wall thickness and chitin content in Δkdnase were confirmed by electron and immunofluorescence microscopy. In a neutropenic mouse model of invasive aspergillosis, the Δkdnase strain had attenuated virulence and a significantly lower lung fungal burden but only in animals that received liposomal amphotericin B after spore exposure. Macrophage numbers were almost twofold higher in lung sections from mice that received the Δkdnase strain, possibly related to higher survival of macrophages that internalized the Δkdnase conidia. Thus, A. fumigatus Kdnase is important for fungal cell wall integrity and virulence, and because Kdnase is not present in the host, it may represent a potential target for the development of novel antifungal agents.

  7. Differential contributions of five ABC transporters to mutidrug resistance, antioxidion and virulence of Beauveria bassiana, an entomopathogenic fungus.

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    Ting-Ting Song

    Full Text Available Multidrug resistance (MDR confers agrochemical compatibility to fungal cells-based mycoinsecticdes but mechanisms involved in MDR remain poorly understood for entomopathogenic fungi, which have been widely applied as biocontrol agents against arthropod pests. Here we characterized the functions of five ATP-binding cassette (ABC transporters, which were classified to the subfamilies ABC-B (Mdr1, ABC-C (Mrp1 and ABC-G (Pdr1, Pdr2 and Pdr5 and selected from 54 full-size ABC proteins of Beauveria bassiana based on their main domain architecture, membrane topology and transcriptional responses to three antifungal inducers. Disruption of each transporter gene resulted in significant reduction in resistance to four to six of eight fungicides or antifungal drugs tested due to their differences in structure and function. Compared with wild-type and complemented (control strains, disruption mutants of all the five transporter genes became significantly less tolerant to the oxidants menadione and H₂O₂ based on 22-41% and 10-31% reductions of their effective concentrations required for the suppression of 50% colony growth at 25°C. Under a standardized spray, the killing actions of ΔPdr5 and ΔMrp1 mutants against Spodoptera litura second-instar larvae were delayed by 59% and 33% respectively. However, no significant virulence change was observed in three other delta mutants. Taken together, the examined five ABC transporters contribute differentially to not only the fungal MDR but antioxidant capability, a phenotype rarely associated with ABC efflux pumps in previous reports; at least some of them are required for the full virulence of B. bassiana, thereby affecting the fungal biocontrol potential. Our results indicate that ABC pump-dependent MDR mechanisms exist in entomopathogenic fungi as do in yeasts and human and plant pathogenic fungi.

  8. Fungal-host diversity among mycoheterotrophic plants increases proportionally to their fungal-host overlap.

    Science.gov (United States)

    Gomes, Sofia I F; Merckx, Vincent S F T; Saavedra, Serguei

    2017-05-01

    The vast majority of plants obtain an important proportion of vital resources from soil through mycorrhizal fungi. Generally, this happens in exchange of photosynthetically fixed carbon, but occasionally the interaction is mycoheterotrophic, and plants obtain carbon from mycorrhizal fungi. This process results in an antagonistic interaction between mycoheterotrophic plants and their fungal hosts. Importantly, the fungal-host diversity available for plants is restricted as mycoheterotrophic interactions often involve narrow lineages of fungal hosts. Unfortunately, little is known whether fungal-host diversity may be additionally modulated by plant-plant interactions through shared hosts. Yet, this may have important implications for plant competition and coexistence. Here, we use DNA sequencing data to investigate the interaction patterns between mycoheterotrophic plants and arbuscular mycorrhizal fungi. We find no phylogenetic signal on the number of fungal hosts nor on the fungal hosts shared among mycoheterotrophic plants. However, we observe a potential trend toward increased phylogenetic diversity of fungal hosts among mycoheterotrophic plants with increasing overlap in their fungal hosts. While these patterns remain for groups of plants regardless of location, we do find higher levels of overlap and diversity among plants from the same location. These findings suggest that species coexistence cannot be fully understood without attention to the two sides of ecological interactions.

  9. Protection by fungal starters against growth and secondary metabolite production of fungal spoilers of cheese.

    Science.gov (United States)

    Nielsen, M S; Frisvad, J C; Nielsen, P V

    1998-06-30

    The influence of fungal starter cultures on growth and secondary metabolite production of fungal contaminants associated with cheese was studied on laboratory media and Camembert cheese. Isolates of the species Penicillium nalgiovense, P. camemberti, P. roqueforti and Geotrichum candidum were used as fungal starters. The species P. commune, P. caseifulvum, P. verrucosum, P. discolor, P. solitum, P. coprophilum and Aspergillus versicolor were selected as contaminants. The fungal starters showed different competitive ability on laboratory media and Camembert cheese. The presence of the Penicillium species, especially P. nalgiovense, showed an inhibitory effect on the growth of the fungal contaminants on laboratory media. G. candidum caused a significant inhibition of the fungal contaminants on Camembert cheese. The results indicate that G. candidum plays an important role in competition with undesirable microorganisms in mould fermented cheeses. Among the starters, P. nalgiovense caused the largest reduction in secondary metabolite production of the fungal contaminants on the laboratory medium. On Camembert cheese no significant changes in metabolite production of the fungal contaminants was observed in the presence of the starters.

  10. Burden of serious fungal infections in Guatemala.

    Science.gov (United States)

    Medina, N; Samayoa, B; Lau-Bonilla, D; Denning, D W; Herrera, R; Mercado, D; Guzmán, B; Pérez, J C; Arathoon, E

    2017-06-01

    Guatemala is a developing country in Central America with a high burden of HIV and endemic fungal infections; we attempted to estimate the burden of serious fungal infections for the country. A full literature search was done to identify epidemiology papers reporting fungal infections from Guatemala. We used specific populations at risk and fungal infection frequencies in the population to estimate national rates. The population of Guatemala in 2013 was 15.4 million; 40% were younger than 15 and 6.2% older than 60. There are an estimated 53,000 adults with HIV infection, in 2015, most presenting late. The estimated cases of opportunistic fungal infections were: 705 cases of disseminated histoplasmosis, 408 cases of cryptococcal meningitis, 816 cases of Pneumocystis pneumonia, 16,695 cases of oral candidiasis, and 4,505 cases of esophageal candidiasis. In the general population, an estimated 5,568 adult asthmatics have allergic bronchopulmonary aspergillosis (ABPA) based on a 2.42% prevalence of asthma and a 2.5% ABPA proportion. Amongst 2,452 pulmonary tuberculosis patients, we estimated a prevalence of 495 for chronic pulmonary aspergillosis in this group, and 1,484 for all conditions. An estimated 232,357 cases of recurrent vulvovaginal candidiasis is likely. Overall, 1.7% of the population are affected by these conditions. The true fungal infection burden in Guatemala is unknown. Tools and training for improved diagnosis are needed. Additional research on prevalence is needed to employ public health measures towards treatment and improving the reported data of fungal diseases.

  11. Leiomyoma-derived transforming growth factor-β impairs bone morphogenetic protein-2-mediated endometrial receptivity.

    Science.gov (United States)

    Doherty, Leo F; Taylor, Hugh S

    2015-03-01

    To determine whether transforming growth factor (TGF)-β3 is a paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein (BMP)-mediated endometrial receptivity and decidualization. Experimental. Laboratory. Women with symptomatic leiomyomas. Endometrial stromal cells (ESCs) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. The TGF-β was blocked by two approaches: TGF-β pan-specific antibody or transfection with a mutant TGF-β receptor type II. Cells were then treated with recombinant human BMP-2 to assess BMP responsiveness. Expression of BMP receptor types 1A, 1B, 2, as well as endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF). Enzyme-linked immunosorbent assay showed elevated TGF-β levels in LCM. LCM treatment of ESC reduced expression of BMP receptor types 1B and 2 to approximately 60% of pretreatment levels. Preincubation of LCM with TGF-β neutralizing antibody or mutant TGF receptor, but not respective controls, prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in recombinant human BMP-2 treated, LCM exposed ESC. Pretreatment of LCM with TGF-β antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Leiomyoma-derived TGF-β was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-β prevents repression of BMP-2 receptors and restores BMP-2-stimulated expression of HOXA10 and LIF. Blockade of TGF signaling is a potential strategy to improve infertility and pregnancy loss associated with uterine leiomyoma. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products.

    Science.gov (United States)

    Bae, Hyun W; Zhao, Li; Kanim, Linda E A; Wong, Pamela; Delamarter, Rick B; Dawson, Edgar G

    2006-05-20

    Enzyme-linked immunosorbent assay was used to detect bone morphogenetic proteins (BMPs) 2, 4, and 7 in 9 commercially available ("off the shelf") demineralized bone matrix (DBM) product formulations using 3 different manufacturer's production lots of each DBM formulation. To evaluate and compare the quantity of BMPs among several different DBM formulations (inter-product variability), as well as examine the variability of these proteins in different production lots within the same DBM formulation (intra-product variability). DBMs are commonly used to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human DBMs from which to choose. Yet, there is limited information on a specific DBM product's osteoinductive efficacy, potency, and constancy. There were protein extracts from each DBM sample separately dialyzed 4 times against distilled water at 4 degrees C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using enzyme-linked immunosorbent assay. RESULTS.: The concentrations of detected BMP-2 and BMP-7 were low for all DBM formulations, only nanograms of BMP were extracted from each gram of DBM (20.2-120.6 ng BMP-2/g DBM product; 54.2-226.8 ng BMP-7/g DBM). The variability of BMP concentrations among different lots of the same DBM formulation, intra-product variability, was higher than the variability of concentrations among different DBM formulations, inter-product variability (coefficient of variation range BMP-2 [16.34% to 76.01%], P DBMs are low, in the order of 1 x 10(-9) g of BMP/g of DBM. There is higher variability in concentration of BMPs among 3 different lots of the same DBM formulation than among different DBM formulations. This variability questions DBM products' reliability and, possibly, efficacy in providing consistent osteoinduction.

  13. Effects of Recombinant Human Bone Morphogenetic Protein-2 on Vertical Bone Augmentation in a Canine Model.

    Science.gov (United States)

    Hsu, Yung-Ting; Al-Hezaimi, Khalid; Galindo-Moreno, Pablo; O'Valle, Francisco; Al-Rasheed, Abdulaziz; Wang, Hom-Lay

    2017-09-01

    Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)-2, under space-making titanium mesh in a canine model. Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP-2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4-month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro-CT) assessment and histologic analysis. Membrane exposure was found on five of 11 (45.5%) rhBMP-2-treated sites, whereas it was found on nine of 11 (81.8%) non-rhBMP-2-treated sites. Within 4 months of healing, rhBMP-2-treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P 0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP-2 sites. With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP-2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non-rhBMP-2 sites.

  14. Heterologous Secretory Expression and Characterization of Dimerized Bone Morphogenetic Protein 2 in Bacillus subtilis

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    Muhammad Umair Hanif

    2017-01-01

    Full Text Available Recombinant human Bone Morphogenetic Protein 2 (rhBMP2 has important applications in the spine fusion and ortho/maxillofacial surgeries. Here we first report the secretory expression of biological active dimerized rhBMP2 from Bacillus subtilis system. The mature domain of BMP2 gene was amplified from pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2-M (single BMP2 gene and pHT43-BMP2-D (two BMP2 genes coupled with a linker to produce a dimer, were designed. After primary cloning (DH5α strain and sequence analysis, constructs were transformed into Bacillus subtilis for secretory expression. Expression conditions like media (2xYT and temperature (30°C were optimized. Maximum 35% and 25% secretory expression of monomer (~13 kDa and dimer (~25 kDa, respectively, were observed on SDS-PAGE in SCK6 strain. The expression and dimeric nature of rhBMP2 were confirmed by western blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5 and Fast Protein Liquid Chromatography (6 ml, Resource Q column was performed. The rhBMP2 monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml was analyzed on C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

  15. Bone Morphogenetic Protein 15 (BMP15) Acts as a BMP and Wnt Inhibitor during Early Embryogenesis*

    Science.gov (United States)

    Di Pasquale, Elisa; Brivanlou, Ali H.

    2009-01-01

    Bone morphogenetic protein 15 (BMP15) belongs to an unusual subgroup of the transforming growth factor β (TGFβ) superfamily of signaling ligands as it lacks a key cysteine residue in the mature region required for proper intermolecular dimerization. Naturally occurring BMP15 mutation leads to early ovarian failure in humans, and BMP15 has been shown to activate the Smad1/5/8 pathway in that context. Despite its important role in germ cell specification, the embryological function of BMP15 remains unknown. Surprisingly, we find that during early Xenopus embryogenesis BMP15 acts solely as an inhibitor of the Smad1/5/8 pathway and the Wnt pathway. BMP15 gain-of-function leads to embryos with secondary ectopic heads and to direct neural induction in intact explants. BMP15 inhibits BMP4-mediated epidermal induction in dissociated explants. BMP15 strongly inhibits BRE response induced by BMP4 and blocks phosphorylation and activation of Smad1/5/8 MH2-domain. Mechanistically, BMP15 protein specifically interacts with BMP4 protein, suggesting inhibition upstream of receptor binding. Loss-of-function experiments using morpholinos or a naturally occurring human BMP15 dominant-negative mutant (BMP15-Y235C) leads to embryos lacking head. BMP15-Y235C also eliminates the inhibitory activity of BMP15 on BRE (BMP-responsive element). Finally, we show that BMP15 inhibits the canonical branch of the Wnt pathway, upstream of β-catenin. We, thus, demonstrate that BMP15 is necessary and sufficient for the specification of dorso-anterior structures and highlight novel mechanisms of BMP15 function that strongly suggest a reinterpretation of its function in ovaries specially for ovarian failure. PMID:19553676

  16. The evaluation of lyophilized polymer matrices for administering recombinant human bone morphogenetic protein-2.

    Science.gov (United States)

    Duggirala, S S; Rodgers, J B; DeLuca, P P

    1996-07-01

    Novel unitary devices, prepared by lyophilization of viscous solutions of sodium carboxymethylcellulose (CMC) and methylcellulose (MC), were evaluated as sustained-release delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). In vitro characterization of the unitary devices, which contained rhBMP-2-loaded poly (d,l lactide-co-glycolide) (PLGA) bioerodible particles (BEPs), was conducted over a 2-month period. Determinations included buffer uptake, mass and molecular weight loss and rhBMP-2 release from the unitary devices. CMC devices imbibed approximately 16 times their weight of buffer, while with MC, equilibrium uptake was approximately 6 times the dry weight of the devices. Overall mass loss percentages were approximately 55 and 35%, respectively, for CMC and MC devices. rhBMP-2 release from the devices was essentially a triphasic process: an initial phase during which "free" protein (rhBMP-2 present on the surface and within the pores of the PLGA BEPs) was released, a lag period during which no release was discerned, and then release of "bound" rhBMP-2 (protein adsorbed to the BEPs). The release of bound protein correlated with the mass loss of the polymer which began after 3 weeks. Release from the unitary devices was lower than that from the BEPs alone, due to a retardation effect of the gelled CMC/MC polymers. In rabbits in which full-thickness cranial bone defects were created, the implants were well tolerated and induced significant new bone growth during an 8-week evaluation period. The CMC devices appear to have induced bone earlier (at 2 weeks), but this did not affect eventual 8-week results. CMC devices without rhBMP-2 appeared to provide some bone conduction, in contrast to the blank MC devices.

  17. Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry.

    Science.gov (United States)

    Siverino, Claudia; Tabisz, Barbara; Lühmann, Tessa; Meinel, Lorenz; Müller, Thomas; Walles, Heike; Nickel, Joachim

    2018-03-29

    Different therapeutic strategies for the treatment of non-healing long bone defects have been intensively investigated. Currently used treatments present several limitations that have led to the use of biomaterials in combination with osteogenic growth factors, such as bone morphogenetic proteins (BMPs). Commonly used absorption or encapsulation methods require supra-physiological amounts of BMP2, typically resulting in a so-called initial burst release effect that provokes several severe adverse side effects. A possible strategy to overcome these problems would be to covalently couple the protein to the scaffold. Moreover, coupling should be performed in a site-specific manner in order to guarantee a reproducible product outcome. Therefore, we created a BMP2 variant, in which an artificial amino acid (propargyl-L-lysine) was introduced into the mature part of the BMP2 protein by codon usage expansion (BMP2-K3Plk). BMP2-K3Plk was coupled to functionalized beads through copper catalyzed azide-alkyne cycloaddition (CuAAC). The biological activity of the coupled BMP2-K3Plk was proven in vitro and the osteogenic activity of the BMP2-K3Plk-functionalized beads was proven in cell based assays. The functionalized beads in contact with C2C12 cells were able to induce alkaline phosphatase (ALP) expression in locally restricted proximity of the bead. Thus, by this technique, functionalized scaffolds can be produced that can trigger cell differentiation towards an osteogenic lineage. Additionally, lower BMP2 doses are sufficient due to the controlled orientation of site-directed coupled BMP2. With this method, BMPs are always exposed to their receptors on the cell surface in the appropriate orientation, which is not the case if the factors are coupled via non-site-directed coupling techniques. The product outcome is highly controllable and, thus, results in materials with homogeneous properties, improving their applicability for the repair of critical size bone defects.

  18. Thumbs down: a molecular-morphogenetic approach to avian digit homology.

    Science.gov (United States)

    Capek, Daniel; Metscher, Brian D; Müller, Gerd B

    2014-01-01

    Avian forelimb digit homology remains one of the standard themes in comparative biology and EvoDevo research. In order to resolve the apparent contradictions between embryological and paleontological evidence a variety of hypotheses have been presented in recent years. The proposals range from excluding birds from the dinosaur clade, to assignments of homology by different criteria, or even assuming a hexadactyl tetrapod limb ground state. At present two approaches prevail: the frame shift hypothesis and the pyramid reduction hypothesis. While the former postulates a homeotic shift of digit identities, the latter argues for a gradual bilateral reduction of phalanges and digits. Here we present a new model that integrates elements from both hypotheses with the existing experimental and fossil evidence. We start from the main feature common to both earlier concepts, the initiating ontogenetic event: reduction and loss of the anterior-most digit. It is proposed that a concerted mechanism of molecular regulation and developmental mechanics is capable of shifting the boundaries of hoxD expression in embryonic forelimb buds as well as changing the digit phenotypes. Based on a distinction between positional (topological) and compositional (phenotypic) homology criteria, we argue that the identity of the avian digits is II, III, IV, despite a partially altered phenotype. Finally, we introduce an alternative digit reduction scheme that reconciles the current fossil evidence with the presented molecular-morphogenetic model. Our approach identifies specific experiments that allow to test whether gene expression can be shifted and digit phenotypes can be altered by induced digit loss or digit gain. © 2013 Wiley Periodicals, Inc.

  19. Morphogenetic events in the perinodal connective tissue in a metastatic cancer model.

    Science.gov (United States)

    Conti, G; Minicozzi, A; Merigo, F; Marzola, P; Osculati, F; Cordiano, C; Sbarbati, A

    2013-02-01

    The modifications of connective tissue surrounding metastatic lymph nodes in a murine model of rectal cancer are described. Athymic nude mice (n=36) were inoculated with 10×10(5) ht-29 cancer cells into the submucosal layer of the rectum. Control mice (n=5) were treated with a sterile buffer. Tumor and the involved lymph nodes were visualized in vivo by magnetic resonance imaging at 1 to 4 weeks after cell injection. After the sacrifice, the excised samples were processed for histology. After one week from cell injection all treated animals developed rectal cancer. Since the first week, neoplastic cells were visible in the nodes. In the surrounding connective tissue, the diameter of the adipocytes was reduced and a mesenchymal-like pattern with stellate cells embedded in an oedematous environment was visible. Since the second week, in the perinodal connective an enlargement of the stroma was present. The tissue was organized in cords and areas with extracellular accumulation of lipids were found. At the fourth week, we observed an enlargement of multilocular areas and lobules of elongated elements almost devoid of lipid droplets. In control animals, in absence of neoplastic masses, pelvic nodes were surrounded by a typical connective tissue characterized by unilocular adipocytes with groups of multilocular adipocytes. We have developed a model of rectal cancer with nodal metastases. Using this model, the work demonstrates that around secondary lesions, the morphogenetic events follow a standard evolution characterized by an early phase with lipolysis and mesenchymalization and later phases with a brown-like phenotype acquisition. Copyright © 2012. Published by Elsevier SAS.

  20. Bone morphogenetic protein 2 and decorin expression in old fracture fragments and surrounding tissues.

    Science.gov (United States)

    Han, X G; Wang, D K; Gao, F; Liu, R H; Bi, Z G

    2015-09-21

    Bone morphogenetic protein 2 (BMP-2) can promote fracture healing. Although the complex role BMP-2 in bone formation is increasingly understood, the role of endogenous BMP-2 in nonunion remains unclear. Decorin (DCN) can promote the formation of bone matrix and calcium deposition to control bone morphogenesis. In this study, tissue composition and expression of BMP-2 and DCN were detected in different parts of old fracture zones to explore inherent anti-fibrotic ability and osteogenesis. Twenty-three patients were selected, including eight cases of delayed union and 15 cases of nonunion. Average duration of delayed union or nonunion was 15 months. Fracture fragments and surrounding tissues, including bone grafts, marrow cavity contents, and sticking scars, were categorically sampled during surgery. Through observation and histological testing, component comparisons were made between fracture fragments and surrounding tissue. The expression levels of DCN and BMP-2 in different tissues were detected by immunohistochemical staining and real-time polymerase chain reaction. The expression of DCN and BMP- 2 in different parts of the nonunion area showed that, compared with bone graft and marrow cavity contents, sticking scars had the highest expression of BMP-2. Compared with the marrow cavity contents and sticking scars, bone grafts had the highest expression of DCN. The low antifibrotic and osteogenic activity of the nonunion area was associated with non-co-expression of BMP-2 and DCN. Therefore, the co-injection of osteogenic factor BMP and DCN into the nonunion area can improve the induction of bone formation and enhance the conversion of the old scar, thereby achieving better nonunion treatment.

  1. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    Science.gov (United States)

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may

  2. Genetic variation in bone morphogenetic protein (BMP) and colon and rectal cancer

    Science.gov (United States)

    Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

    2011-01-01

    Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs), and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n=1574 cases, 1970 controls; rectal cancer n=791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2, and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR 2.49 95% CI 1.95, 3.18). BMPR2, BMPR1B, BMP2, and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-β-signaling pathway, including TGFβ1, TGFβR1, Smad 3, Smad 4, and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-β-signaling pathway. PMID:21387313

  3. Cathepsin H indirectly regulates morphogenetic protein-4 (BMP-4) in various human cell lines

    Science.gov (United States)

    Rojnik, Matija; Jevnikar, Zala; Mirkovic, Bojana; Janes, Damjan; Zidar, Nace; Kikelj, Danijel; Kos, Janko

    2011-01-01

    Background Cathepsin H is a cysteine protease considered to play a major role in tumor progression, however, its precise function in tumorigenesis is unclear. Cathepsin H was recently proposed to be involved in processing of bone morphogenetic protein 4 (BMP-4) in mice. In order to clarify whether cathepsin H also regulates BMP-4 in humans, its impact on BMP-4 expression, processing and degradation was investigated in prostate cancer (PC-3), osteosarcoma (HOS) and pro-monocytic (U937) human cell lines. Materials and methods BMP-4 expression was founded to be regulated by cathepsin H using PCR array technology and confirmed by real time PCR. Immunoassays including Western blot and confocal microscopy were used to evaluate the influence of cathepsin H on BMP-4 processing. Results In contrast to HOS, the expression of BMP-4 mRNA in U937 and PC3 cells was significantly decreased by cathepsin H. The different regulation of BMP-4 synthesis could be associated with the absence of the mature 28 kDa cathepsin H form in HOS cells, where only the intermediate 30 kDa form was observed. No co-localization of BMP-4 and cathepsin H was observed in human cell lines and the multistep processing of BMP-4 was not altered in the presence of specific cathepsin H inhibitor. Isolated cathepsin H does not cleave mature recombinant BMP-4, neither with its amino- nor its endopeptidase activity. Conclusions Our results exclude direct proteolytic processing of BMP-4 by cathepsin H, however, they provide support for its involvement in the regulation of BMP-4 expression. PMID:22933963

  4. Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.

    Science.gov (United States)

    Takata, Munetomo; Sugimoto, Naotoshi; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Nishida, Hideji; Tanzawa, Yoshikazu; Kimura, Hiroaki; Miwa, Shinji; Takeuchi, Akihiko; Tsuchiya, Hiroyuki

    2011-12-01

    Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

    Science.gov (United States)

    Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

    2011-05-01

    The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

  6. Information transmission in microbial and fungal communication: from classical to quantum.

    Science.gov (United States)

    Majumdar, Sarangam; Pal, Sukla

    2018-06-01

    Microbes have their own communication systems. Secretion and reception of chemical signaling molecules and ion-channels mediated electrical signaling mechanism are yet observed two special ways of information transmission in microbial community. In this article, we address the aspects of various crucial machineries which set the backbone of microbial cell-to-cell communication process such as quorum sensing mechanism (bacterial and fungal), quorum sensing regulated biofilm formation, gene expression, virulence, swarming, quorum quenching, role of noise in quorum sensing, mathematical models (therapy model, evolutionary model, molecular mechanism model and many more), synthetic bacterial communication, bacterial ion-channels, bacterial nanowires and electrical communication. In particular, we highlight bacterial collective behavior with classical and quantum mechanical approaches (including quantum information). Moreover, we shed a new light to introduce the concept of quantum synthetic biology and possible cellular quantum Turing test.

  7. Virulence of Rhodococcus equi Isolated from Cats and Dogs

    OpenAIRE

    Takai, Shinji; Martens, Ronald J.; Julian, Alan; Garcia Ribeiro, Márcio; Rodrigues de Farias, Marconi; Sasaki, Yukako; Inuzuka, Kazuho; Kakuda, Tsutomu; Tsubaki, Shiro; Prescott, John F.

    2003-01-01

    Nine cat isolates and nine dog isolates of Rhodococcus equi from clinical material were investigated for the presence of the virulence-associated antigens (VapA and VapB) and virulence plasmids. Five of the cat isolates and one dog isolate were VapA positive and contained an 85-kb type I or an 87-kb type I plasmid. The remaining 12 isolates were avirulent R. equi strains and contained no virulence plasmids.

  8. Fungal Genomics for Energy and Environment

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2013-03-11

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Sequencing Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 200 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  9. Fungal endophytes: modifiers of plant disease.

    Science.gov (United States)

    Busby, Posy E; Ridout, Mary; Newcombe, George

    2016-04-01

    Many recent studies have demonstrated that non-pathogenic fungi within plant microbiomes, i.e., endophytes ("endo" = within, "phyte" = plant), can significantly modify the expression of host plant disease. The rapid pace of advancement in endophyte ecology warrants a pause to synthesize our understanding of endophyte disease modification and to discuss future research directions. We reviewed recent literature on fungal endophyte disease modification, and here report on several emergent themes: (1) Fungal endophyte effects on plant disease span the full spectrum from pathogen antagonism to pathogen facilitation, with pathogen antagonism most commonly reported. (2) Agricultural plant pathosystems are the focus of research on endophyte disease modification. (3) A taxonomically diverse group of fungal endophytes can influence plant disease severity. And (4) Fungal endophyte effects on plant disease severity are context-dependent. Our review highlights the importance of fungal endophytes for plant disease across a broad range of plant pathosystems, yet simultaneously reveals that complexity within plant microbiomes presents a significant challenge to disentangling the biotic environmental factors affecting plant disease severity. Manipulative studies integrating eco-evolutionary approaches with emerging molecular tools will be poised to elucidate the functional importance of endophytes in natural plant pathosystems that are fundamental to biodiversity and conservation.

  10. Phylogenetic analysis of fungal ABC transporters.

    Science.gov (United States)

    Kovalchuk, Andriy; Driessen, Arnold J M

    2010-03-16

    The superfamily of ABC proteins is among the largest known in nature. Its members are mainly, but not exclusively, involved in the transport of a broad range of substrates across biological membranes. Many contribute to multidrug resistance in microbial pathogens and cancer cells. The diversity of ABC proteins in fungi is comparable with those in multicellular animals, but so far fungal ABC proteins have barely been studied. We performed a phylogenetic analysis of the ABC proteins extracted from the genomes of 27 fungal species from 18 orders representing 5 fungal phyla thereby covering the most important groups. Our analysis demonstrated that some of the subfamilies of ABC proteins remained highly conserved in fungi, while others have undergone a remarkable group-specific diversification. Members of the various fungal phyla also differed significantly in the number of ABC proteins found in their genomes, which is especially reduced in the yeast S. cerevisiae and S. pombe. Data obtained during our analysis should contribute to a better understanding of the diversity of the fungal ABC proteins and provide important clues about their possible biological functions.

  11. Fungal endophytes for sustainable crop production.

    Science.gov (United States)

    Lugtenberg, Ben J J; Caradus, John R; Johnson, Linda J

    2016-12-01

    This minireview highlights the importance of endophytic fungi for sustainable agriculture and horticulture production. Fungal endophytes play a key role in habitat adaptation of plants resulting in improved plant performance and plant protection against biotic and abiotic stresses. They encode a vast variety of novel secondary metabolites including volatile organic compounds. In addition to protecting plants against pathogens and pests, selected fungal endophytes have been used to remove animal toxicities associated with fungal endophytes in temperate grasses, to create corn and rice plants that are tolerant to a range of biotic and abiotic stresses, and for improved management of post-harvest control. We argue that practices used in plant breeding, seed treatments and agriculture, often caused by poor knowledge of the importance of fungal endophytes, are among the reasons for the loss of fungal endophyte diversity in domesticated plants and also accounts for the reduced effectiveness of some endophyte strains to confer plant benefits. We provide recommendations on how to mitigate against these negative impacts in modern agriculture. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Fueling the Future with Fungal Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2014-10-27

    Genomes of fungi relevant to energy and environment are in focus of the JGI Fungal Genomic Program. One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts and pathogens) and biorefinery processes (cellulose degradation and sugar fermentation) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Science Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 400 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics will lead to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such ‘parts’ suggested by comparative genomics and functional analysis in these areas are presented here.

  13. Mutations induced by ultraviolet radiation affecting virulence in Puccinia striiformis

    International Nuclear Information System (INIS)

    Shang Hongsheng; Jing Jinxue; Li Zhenqi

    1994-01-01

    Uredospores of parent culture, cy 29-1, were treated by ultraviolet radiation and mutations to virulent were tested on resistant wheat cultivars inoculated with treated spores. 7 mutant cultures virulent to the test cultivars were developed with estimated mutation rate 10~6~10~4. The virulence of mutant cultures was different from the all known races of stripe rust. Resistance segregation to mutant cultures was detected in two test cultivars. The results suggested that mutation was important mechanism of virulence variation operative in asexual population of rust fungi

  14. Limiting opportunities for cheating stabilizes virulence in insect parasitic nematodes.

    Science.gov (United States)

    Shapiro-Ilan, David; Raymond, Ben

    2016-03-01

    Cooperative secretion of virulence factors by pathogens can lead to social conflict when cheating mutants exploit collective secretion, but do not contribute to it. If cheats outcompete cooperators within hosts, this can cause loss of virulence. Insect parasitic nematodes are important biocontrol tools that secrete a range of significant virulence factors. Critically, effective nematodes are hard to maintain without live passage, which can lead to virulence attenuation. Using experimental evolution, we tested whether social cheating might explain unstable virulence in the nematode Heterorhabditis floridensis by manipulating relatedness via multiplicity of infection (MOI), and the scale of competition. Passage at high MOI, which should reduce relatedness, led to loss of fitness: virulence and reproductive rate declined together and all eight independent lines suffered premature extinction. As theory predicts, relatedness treatments had more impact under stronger global competition. In contrast, low MOI passage led to more stable virulence and increased reproduction. Moreover, low MOI lineages showed a trade-off between virulence and reproduction, particularly for lines under stronger between-host competition. Overall, this study indicates that evolution of virulence theory is valuable for the culture of biocontrol agents: effective nematodes can be improved and maintained if passage methods mitigate possible social conflicts.

  15. Convergent evolution of morphogenetic processes in fungi: Role of tetraspanins and NADPH oxidases 2 in plant pathogens and saprobes.

    Science.gov (United States)

    Malagnac, Fabienne; Bidard, Frédérique; Lalucque, Hervé; Brun, Sylvain; Lambou, Karine; Lebrun, Marc-Henri; Silar, Philippe

    2008-01-01

    Convergent evolution of trophic life style and morphological characters are very common in the fungal kingdom. Recently, we have shown that the same molecular machinery containing a tetraspanin and a NADPH oxidase has been recruited in two different fungal species for the same purpose (exiting from a melanized re-enforced cell at a focal weakened point), but at different stages of their development (ascospore germination and appressorium mediated penetration). Although this molecular machinery is required at these key developmental steps, it is also likely involved in specialized cellular functions at other stages of fungal development, as shown here for nutrient acquisition by Podospora anserina.

  16. Molecular Diagnostics for Soilborne Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    E.J. Paplomatas

    2004-08-01

    Full Text Available Several classical approaches have been developed to detect and identify soil fungal inhabitants through the years. Selective media have been devised to exclude the large number of soil organisms and allow growth of target fungi. However the advent of molecular biology has offered a number of revolutionary insights into the detection and enumeration of soilborne fungal pathogens and also has started to provide information on the identification of unknown species from DNA sequences. This review paper focuses on the application of various molecular techniques in the detection, identification, characterization and quantification of soilborne fungal plant pathogens. This is based on information from the literature and is combined with personal research findings of the author.

  17. Fungal endophytes of sorghum in Burkina Faso

    DEFF Research Database (Denmark)

    Zida, E P; Thio, I G; Néya, B J

    2014-01-01

    A survey was conducted to assess the natural occurrence and distribution of fungal endophytes in sorghum in relation to plant performance in two distinct agro-ecological zones in Burkina Faso. Sorghum farm-saved seeds were sown in 48 farmers’ fields in Sahelian and North Sudanian zones to produce...... sorghum plants. In each field, leaf samples were collected from five well-developed (performing) and five less-developed (non-performing) plants at 3-5 leaf stage, while at plant maturity leaf, stem and root samples were collected from the same plants and fungal endophytes were isolated. A total of 39...... fungal species belonging to 25 genera were isolated. The most represented genera included Fusarium, Leptosphaeria, Curvularia, Nigrospora and Penicillium. The genera Fusarium and Penicillium occurred significantly higher in performing plants as compared to non-performing plants while the genera...

  18. The autophagy-related genes BbATG1 and BbATG8 have different functions in differentiation, stress resistance and virulence of mycopathogen Beauveria bassiana

    Science.gov (United States)

    Ying, Sheng-Hua; Liu, Jing; Chu, Xin-Ling; Xie, Xue-Qin; Feng, Ming-Guang

    2016-01-01

    Autophagy-related proteins play significantly different roles in eukaryotes. In the entomopathogenic fungus Beauveria bassiana, autophagy is associated with fungal growth and development. BbATG1 (a serine/threonine protein kinase) and BbATG8 (a ubiquitin-like protein) have similar roles in autophagy, but different roles in other processes. Disruption mutants of BbATG1 and BbATG8 had impaired conidial germination under starvation stress. The mutant ΔBbATG8 exhibited enhanced sensitivity to oxidative stress, while a ΔBbATG1 mutant did not. BbATG1 and BbATG8 showed different roles in spore differentiation. The blastospore yield was reduced by 70% and 92% in ΔBbATG1 and ΔBbATG8 mutants, respectively, and the double mutant had a reduction of 95%. Conidial yield was reduced by approximately 90% and 50% in ΔBbATG1 and ΔBbATG8 mutants, respectively. A double mutant had a reduction similar to ΔBbATG1. Additionally, both BbATG1 and BbATG8 affected the levels of conidial protein BbCP15p required for conidiation. The virulence of each autophagy-deficient mutant was considerably weakened as indicated in topical and intrahemocoel injection assays, and showed a greater reduction in topical infection. However, BbATG1 and BbATG8 had different effects on fungal virulence. Our data indicate that these autophagy-related proteins have different functions in fungal stress response, asexual development and virulence. PMID:27197558

  19. Omics strategies for revealing Yersinia pestis virulence

    Science.gov (United States)

    Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

    2012-01-01

    Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

  20. Virulence determinants of pandemic influenza viruses

    Science.gov (United States)

    Tscherne, Donna M.; García-Sastre, Adolfo

    2011-01-01

    Influenza A viruses cause recurrent, seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. The ability of influenza A viruses to adapt to various hosts and undergo reassortment events ensures constant generation of new strains with unpredictable degrees of pathogenicity, transmissibility, and pandemic potential. Currently, the combination of factors that drives the emergence of pandemic influenza is unclear, making it impossible to foresee the details of a future outbreak. Identification and characterization of influenza A virus virulence determinants may provide insight into genotypic signatures of pathogenicity as well as a more thorough understanding of the factors that give rise to pandemics. PMID:21206092

  1. Metal acquisition and virulence in Brucella

    Science.gov (United States)

    Roop, R. Martin

    2013-01-01

    Similar to other bacteria, Brucella strains require several biologically essential metals for their survival in vitro and in vivo. Acquiring sufficient levels of some of these metals, particularly iron, manganese and zinc, is especially challenging in the mammalian host, where sequestration of these micronutrients is a well-documented component of both the innate and acquired immune responses. This review describes the Brucella metal transporters that have been shown to play critical roles in the virulence of these bacteria in experimental and natural hosts. PMID:22632611

  2. Landforms and morphogenetic processes in the locality of Geodetic Observatory Pecný, Ondřejovská vrchovina Highland

    Directory of Open Access Journals (Sweden)

    Tereza Steklá

    2017-03-01

    In the rugged terrain of the GOPE locality, there are visible marks of regelation and frost processes, gully and fluvial erosion, slow slope movements and anthropogenic activities. Intensity of recent morphogenetic processes with its maximum in spring corresponds to combination of seasonal changes of air and soil temperature and at the same time to increased water content in the rock massif and in the weathered mantle. The suitable geodynamic location of scientific observatories on the Pecný ridge, stable from engineering-geological and geomorphological point of view, and in its near neighbourhood is menaced by increasing intensity of anthropogenic activities in the landscape.

  3. [Morphogenetic processes and seasonal changes in the anatomic and histological organization of the Barents Sea sponge Halichondria panicea (Pallas)].

    Science.gov (United States)

    Ivanova, L V

    1978-10-01

    As a result of histological investigations of seasonal dynamics in the anatomical-tissue organization of the litoral sponge Halichondria panicea (Pallas), morphogenetical processes during different periods of its life cycle are described in detail. Correlations between different phases of sexual reproduction and conditions of anatomical and tissue organization in the maternal organism are stated. It is noted that tissue reduction of the definitive sponge Halichondria panicea during autumn--winter season is a natural phenomenon, regularly repeating in the life of the litoral sponge investigated, as a result of the maternal organism's "exhaustion" in the period of sexual embryogenesis.

  4. Identification & Characterization of Fungal Ice Nucleation Proteins

    Science.gov (United States)

    Scheel, Jan Frederik; Kunert, Anna Theresa; Kampf, Christopher Johannes; Mauri, Sergio; Weidner, Tobias; Pöschl, Ulrich; Fröhlich-Nowoisky, Janine

    2016-04-01

    Freezing of water at relatively warm subfreezing temperatures is dependent on ice nucleation catalysis facilitated by ice nuclei (IN). These IN can be of various origins and although extensive research was done and progress was achieved, the nature and mechanisms leading to an effective IN are to date still poorly understood. Some of the most important processes of our geosphere like the water cycle are highly dependent on effective ice nucleation at temperatures between -2°C - -8°C, a temperature range which is almost exclusively covered by biological IN (BioIN). BioIN are usually macromolecular structures of biological polymers. Sugars as well as proteins have been reported to serve as IN and the best characterized BioIN are ice nucleation proteins (IN-P) from gram negative bacteria. Fungal strains from Fusarium spp. were described to be effective IN at subfreezing temperatures up to -2°C already 25 years ago and more and more fungal species are described to serve as efficient IN. Fungal IN are also thought to be proteins or at least contain a proteinaceous compound, but to date the fungal IN-P primary structure as well as their coding genetic elements of all IN active fungi are unknown. The aim of this study is a.) to identify the proteins and their coding genetic elements from IN active fungi (F. acuminatum, F. avenaceum, M. alpina) and b.) to characterize the mechanisms by which fungal IN serve as effective IN. We designed an interdisciplinary approach using biological, analytical and physical methods to identify fungal IN-P and describe their biological, chemical, and physical properties.

  5. Mucormycosis: a devastating fungal infection in diabetics

    International Nuclear Information System (INIS)

    Rashid, M.; Bari, A.; Mehmood, S.; Tariq, K.M.; Haq, I.; Niwaz, Z.

    2005-01-01

    Mucormycosis is a highly invasive, devastating and usually fatal fungal infection of the sinuses, brain, or lungs that occurs primarily in people with immune disorders. Despite advances in diagnosis and treatment, a high mortality still exists. We present a middle aged diabetic male with this serious fungal infection involving nose, paranasal area and adjacent periorbital regions with a high risk of progressing further towards the dura mater. He was promptly diagnosed and managed with serial surgical debridements with systemic antifungals and was later fitted with a nasal prosthesis. (author)

  6. Fungal infections of the lung in children

    Energy Technology Data Exchange (ETDEWEB)

    Toma, Paolo; Colafati, Giovanna Stefania; D' Andrea, Maria Luisa [IRCCS Bambino Gesu Children' s Hospital, Department of Imaging, Rome (Italy); Bertaina, Alice; Mastronuzzi, Angela [IRCCS Bambino Gesu Children' s Hospital, Department of Pediatric Hematology/Oncology and Transfusion Medicine, Rome (Italy); Castagnola, Elio [IRCCS Istituto Giannina Gaslini, Department of Infective Diseases, Genoa (Italy); Finocchi, Andrea [IRCCS Bambino Gesu Children' s Hospital, Department of Pediatrics, Rome (Italy); Lucidi, Vincenzina [IRCCS Bambino Gesu Children' s Hospital, Cystic Fibrosis Center, Rome (Italy); Granata, Claudio [IRCCS Istituto Giannina Gaslini, Department of Pediatric Radiology, Genoa (Italy)

    2016-12-15

    Fungal infections of the lungs are relatively common and potentially life-threatening conditions in immunocompromised children. The role of imaging in children with lung mycosis is to delineate the extension of pulmonary involvement, to assess response to therapy, and to monitor for adverse sequelae such as bronchiectasis and cavitation. The aim of this paper is to show imaging findings in a series of patients with fungal pneumonia from two tertiary children's hospitals, to discuss differential diagnoses and to show how imaging findings can vary depending on the host immune response. (orig.)

  7. Cell cycle and cell death are not necessary for appressorium formation and plant infection in the fungal plant pathogen Colletotrichum gloeosporioides

    Directory of Open Access Journals (Sweden)

    Barhoom Sima

    2008-02-01

    Full Text Available Abstract Background In order to initiate plant infection, fungal spores must germinate and penetrate into the host plant. Many fungal species differentiate specialized infection structures called appressoria on the host surface, which are essential for successful pathogenic development. In the model plant pathogen Magnaporthe grisea completion of mitosis and autophagy cell death of the spore are necessary for appressoria-mediated plant infection; blocking of mitosis prevents appressoria formation, and prevention of autophagy cell death results in non-functional appressoria. Results We found that in the closely related plant pathogen Colletotrichum gloeosporioides, blocking of the cell cycle did not prevent spore germination and appressoria formation. The cell cycle always lagged behind the morphogenetic changes that follow spore germination, including germ tube and appressorium formation, differentiation of the penetrating hypha, and in planta formation of primary hyphae. Nuclear division was arrested following appressorium formation and was resumed in mature appressoria after plant penetration. Unlike in M. grisea, blocking of mitosis had only a marginal effect on appressoria formation; development in hydroxyurea-treated spores continued only for a limited number of cell divisions, but normal numbers of fully developed mature appressoria were formed under conditions that support appressoria formation. Similar results were also observed in other Colletotrichum species. Spores, germ tubes, and appressoria retained intact nuclei and remained viable for several days post plant infection. Conclusion We showed that in C. gloeosporioides the differentiation of infection structures including appressoria precedes mitosis and can occur without nuclear division. This phenomenon was also found to be common in other Colletotrichum species. Spore cell death did not occur during plant infection and the fungus primary infection structures remained viable

  8. [Investigation of some virulence factors in Trichosporon spp. strains].

    Science.gov (United States)

    Demir, Feyza; Kuştimur, Semra

    2014-10-01

    The frequency of fungal infections have increased recently in parallel to prolonged survival of patients with chronical infections, common use of the broad-spectrum antibiotics and cytotoxic drugs and surgical interventions. Fungi such as Trichosporon, Fusarium and Geotrichum that were previously evaluated as contaminant/colonization, become important causes of morbidity and mortality especially in neutropenic patients. The aim of this study was to investigate the presence of virulence factors such as acid proteinase, phospholipase, esterase, coagulase and hemolytic activity among Trichosporon species. A total of 40 Trichosporon strains, of them 24 (60%) were T.asahii, 6 (15%) were T.inkin and 10 (25%) were the other species (one of each of T.aquatile, T.asteroides, T.coremiiforme, T.cutaneum, T.dermatis, T.faecale, T.japonicum, T.montevideense, T.mucoides, T.ovoides) were included in the study. Identification of the isolates was performed according to microscopic morphology (blastospores, arthrospores, pseudohyphae and true hyphae) on corn meal agar media, and carbohydrate assimilation patterns (API ID32C; bioMérieux, France). Secretory acid proteinase, phospholipase and esterase activities of the strains were evaluated by 1% bovine serum albumin containing agar, by egg yolk containing solid medium, and by Tween 80 containing solid medium, respectively. Hemolytic activity of the isolates were evaluated by 5-10% sheep blood Sabouraud dextrose agar. Coagulase enzyme activity was determined by using human and rabbit plasma. In our study, all of the 40 Trichosporon spp. strains were found negative in terms of acid proteinase and phospholipase enzyme activity, however all were positive for esterase enzyme activity. Hemolytic enzyme activity were identified in a total of 15 (37.5%) strains, being "+++" in three strains (2 T.asahii, 1 T.japonicum), and "++" in 12 isolates (9 T.asahii, 1 T.inkin, 1 T.asteroides, 1 T.mentevideense). Although 11 of those 15 positive

  9. Proteomic Investigation of Rhizoctonia solani AG 4 Identifies Secretome and Mycelial Proteins with roles in Plant Cell Wall Degradation and Virulence

    KAUST Repository

    Lakshman, Dilip; Roberts, Daniel P.; Garrett, Wesley M.; Natarajan, Savithiry S.; Darwish, Omar; Alkharouf, Nadim; Pain, Arnab; Khan, Farooq; Jambhulkar, Prashant P.; Mitra, Amitava

    2016-01-01

    Rhizoctonia solani AG 4 is a soilborne necrotrophic fungal plant pathogen that causes economically important diseases on agronomic crops worldwide. Here we used a proteomics approach to characterize both intracellular proteins and the secretome of R. solani AG 4 isolate Rs23A under several growth conditions; the secretome being highly important in pathogenesis. From over 500 total secretome and soluble intracellular protein spots from 2-D gels, 457 protein spots were analyzed and 318 proteins positively matched with fungal proteins of known function by comparison with available R. solani genome databases specific for anastomosis groups 1-IA, 1-IB, and 3. These proteins were categorized to possible cellular locations and functional groups; and for some proteins their putative roles in plant cell wall degradation and virulence. The majority of the secreted proteins were grouped to extracellular regions and contain hydrolase activity.

  10. Proteomic Investigation of Rhizoctonia solani AG 4 Identifies Secretome and Mycelial Proteins with roles in Plant Cell Wall Degradation and Virulence

    KAUST Repository

    Lakshman, Dilip

    2016-03-28

    Rhizoctonia solani AG 4 is a soilborne necrotrophic fungal plant pathogen that causes economically important diseases on agronomic crops worldwide. Here we used a proteomics approach to characterize both intracellular proteins and the secretome of R. solani AG 4 isolate Rs23A under several growth conditions; the secretome being highly important in pathogenesis. From over 500 total secretome and soluble intracellular protein spots from 2-D gels, 457 protein spots were analyzed and 318 proteins positively matched with fungal proteins of known function by comparison with available R. solani genome databases specific for anastomosis groups 1-IA, 1-IB, and 3. These proteins were categorized to possible cellular locations and functional groups; and for some proteins their putative roles in plant cell wall degradation and virulence. The majority of the secreted proteins were grouped to extracellular regions and contain hydrolase activity.

  11. Virulence-associated gene profiling of Streptococcus suis isolates by PCR

    NARCIS (Netherlands)

    Silva, L.M.G.; Baums, C.G.; Rehm, T.; Wisselink, H.J.; Goethe, R.; Valentin-Weigand, P.

    2006-01-01

    Definition of virulent Streptococcus suis strains is controversial. One successful approach for identification of virulent European strains is differentiation of capsular serotypes (or the corresponding cps types) and subsequent detection of virulence-associated factors, namely the extracellular

  12. Expression of human bone morphogenetic protein (BMP-2 and BMP-4 genes in transgenic bovine fibroblasts Expressão dos genes bone morphogenetic protein (BMP-2 e BMP-4 em fibroblastos bovinos transgênicos

    Directory of Open Access Journals (Sweden)

    C. Oleskovicz

    2004-08-01

    Full Text Available cDNAs dos genes bone morphogenetic protein-2 (BMP-2 e bone morphogenetic protein-4 (BMP-4 foram sintetizados a partir de RNA total extraído de tecidos ósseos de pacientes que apresentavam trauma facial (fraturas do maxilar entre o 7º e o 10º dia pós-trauma e clonados num vetor para expressão em células mamíferas, sob controle do promotor de citomegalovírus (CMV. Os vetores contendo os genes BMP-2 e o BMP-4 foram utilizados para a transfecção de fibroblastos bovinos. mRNAs foram indiretamente detectados por RT-PCR nas células transfectadas. As proteínas BMP-2 e BMP-4 foram detectadas mediante análises de Western blot. Os resultados demonstram a possibilidade de produção desses fatores de crescimento celular em fibroblastos bovinos. Essas células poderão ser utilizadas como fontes doadoras de material genético para a técnica de transferência nuclear na geração de animais transgênicos.

  13. 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

  14. 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

  15. MycoCosm, an Integrated Fungal Genomics Resource

    Energy Technology Data Exchange (ETDEWEB)

    Shabalov, Igor; Grigoriev, Igor

    2012-03-16

    MycoCosm is a web-based interactive fungal genomics resource, which was first released in March 2010, in response to an urgent call from the fungal community for integration of all fungal genomes and analytical tools in one place (Pan-fungal data resources meeting, Feb 21-22, 2010, Alexandria, VA). MycoCosm integrates genomics data and analysis tools to navigate through over 100 fungal genomes sequenced at JGI and elsewhere. This resource allows users to explore fungal genomes in the context of both genome-centric analysis and comparative genomics, and promotes user community participation in data submission, annotation and analysis. MycoCosm has over 4500 unique visitors/month or 35000+ visitors/year as well as hundreds of registered users contributing their data and expertise to this resource. Its scalable architecture allows significant expansion of the data expected from JGI Fungal Genomics Program, its users, and integration with external resources used by fungal community.

  16. Porphyromonas gingivalis : Its virulence and vaccine

    Directory of Open Access Journals (Sweden)

    Nymphea Pandit

    2015-01-01

    Full Text Available Background: The microbial florae in adult periodontitis lesions are comprised of anaerobic rods with Porphyromonas gingivalis as one of the major components (Slots 1976; Slots 1979; and Tanner et al., 1979. P. gingivalis is a black-pigmented gram-negative anaerobic rod and a secondary colonizer of dental plaque requiring antecedent organisms. The presence of this organism either alone or as a mixed infection with other bacteria and with the absence of beneficial species appears to be essential for disease activity. It is a predominant member of the subgingival microbiota in disease. It possesses and "excretes" numerous potentially toxic virulence factors. Aim of this study is to perform a systematic review of studies on P. gingivalis and its virulence factors with a special focus on its vaccine. Materials and Methods: An electronic and manual search based on agreed search phrases between the primary investigator and a secondary investigator was performed for the literature review till January 2014. The articles that were identified by this systematic review (total of 190 were analyzed in detail, which included the study of inference and conclusion. Conclusions: Within the limits of this systematic review, it can be concluded that P. gingivalis induce immune inflammatory response in periodontitis subjects. Therapeutic vaccines need to be developed and studied for their efficacy in controlling periodontitis.

  17. Metabolism and virulence in Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Christoph eSchoen

    2014-08-01

    Full Text Available A longstanding question in infection biology addresses the genetic basis for invasive behaviour in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

  18. Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3.

    Science.gov (United States)

    Dwivedi, Prem P; Grose, Randall H; Filmus, Jorge; Hii, Charles S T; Xian, Cory J; Anderson, Peter J; Powell, Barry C

    2013-08-01

    From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates. One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures. Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation. Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children. Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated. We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media. We show that they inhibit BMP2, BMP4 and BMP7 activities, which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity. In contrast, increased levels of GPC1 and GPC3 as a result of overexpression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis. We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways. GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein. The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis, and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how downregulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Characterization of a morphogenetic furrow specific Gal4 driver in the developing Drosophila eye.

    Directory of Open Access Journals (Sweden)

    Ankita Sarkar

    Full Text Available The ability to express a gene of interest in a spatio-temporal manner using Gal4-UAS system has allowed the use of Drosophila model to study various biological phenomenon. During Drosophila eye development, a synchronous wave of differentiation called Morphogenetic furrow (MF initiates at the posterior margin resulting in differentiation of retinal neurons. This synchronous differentiation is also observed in the differentiating retina of vertebrates. Since MF is highly dynamic, it can serve as an excellent model to study patterning and differentiation. However, there are not any Gal4 drivers available to observe the gain- of- function or loss- of- function of a gene specifically along the dynamic MF. The decapentaplegic (dpp gene encodes a secreted protein of the transforming growth factor-beta (TGF-beta superfamily that expresses at the posterior margin and then moves with the MF. However, unlike the MF associated pattern of dpp gene expression, the targeted dpp-Gal4 driver expression is restricted to the posterior margin of the developing eye disc. We screened GMR lines harboring regulatory regions of dpp fused with Gal4 coding region to identify MF specific enhancer of dpp using a GFP reporter gene. We employed immuno-histochemical approaches to detect gene expression. The rationale was that GFP reporter expression will correspond to the dpp expression domain in the developing eye. We identified two new dpp-Gal4 lines, viz., GMR17E04-Gal4 and GMR18D08-Gal4 that carry sequences from first intron region of dpp gene. GMR17E04-Gal4 drives expression along the MF during development and later in the entire pupal retina whereas GMR18D08-Gal4 drives expression of GFP transgene in the entire developing eye disc, which later drives expression only in the ventral half of the pupal retina. Thus, GMR18D08-Gal4 will serve as a new reagent for targeting gene expression in the ventral half of the pupal retina. We compared misexpression phenotypes of Wg, a

  20. Bone Morphogenetic Protein (BMP-7 expression is decreased in human hypertensive nephrosclerosis

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    Cohen Clemens D

    2010-11-01

    Full Text Available Abstract Background Bone Morphogenetic Protein (BMP-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8 expression was quantified in proximal tubular cells (HK-2. Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT, expression of TGF-β receptor type I (TGF-βRI and phosphorylated Smad 2 (pSmad 2 as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

  1. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  2. Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis.

    Science.gov (United States)

    Carragee, Eugene J; Chu, Gilbert; Rohatgi, Rajat; Hurwitz, Eric L; Weiner, Bradley K; Yoon, S Tim; Comer, Garet; Kopjar, Branko

    2013-09-04

    Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor known to have in vitro effects on the growth and invasiveness of cancer. It has been approved by the U.S. Food and Drug Administration in limited doses for single-level anterior spinal arthrodesis, but it is commonly used off-label and at high doses. The effect of rhBMP-2 on the risk of cancer has been a concern. We sought to evaluate the risk of new cancers in patients receiving high-dose rhBMP-2. We used publicly available data from a pivotal, multicenter, randomized controlled trial of patients with degenerative lumbar spine conditions who underwent a single-level instrumented posterolateral arthrodesis with either high-dose rhBMP-2 in a compression-resistant matrix (CRM) (rhBMP-2/CRM; n = 239) or autogenous bone graft (control group; n = 224). We compared the risks of new cancers in the rhBMP-2/CRM and control groups at two and five years after surgery. At two years, with 86% follow-up, there were fifteen new cancer events in eleven patients in the rhBMP-2/CRM group compared with two new cancer events in two patients in the control group treated with autogenous bone graft. The incidence rate of new cancer events per 100 person-years was 3.37 (95% confidence interval [CI], 1.89 to 5.56) in the rhBMP-2/CRM group at two years compared with 0.50 (95% CI, 0.06 to 1.80) in the control group. The incidence rate ratio was 6.75 (95% CI, 1.57 to 60.83; p = 0.0026) at two years. Calculated in terms of the number of patients with one or more cancer events two years after the surgery, the incidence rate per 100 person-years was 2.54 (95% CI, 1.27 to 4.54) in the rhBMP-2/CRM group compared with 0.50 (95% CI, 0.06 to 1.82) in the control group at two years; the incidence rate ratio was 5.04 (95% CI, 1.10 to 46.82; p = 0.0194). At five years, there was a 37% loss of follow-up, but a significantly greater incidence of cancer events was still observed in the rhBMP-2/CRM group. A high dose of 40 mg of rh

  3. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

    Science.gov (United States)

    Tian, Xiao-bin; Sun, Li; Yang, Shu-hua; Zhang, Yu-kun; Hu, Ru-yin; Fu, De-hao

    2008-04-20

    Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone

  4. Fungal Zinc Homeostasis - A Tug of War Between the Pathogen and Host.

    Science.gov (United States)

    Walencik, Paulina K; Watly, Joanna; Rowinska-Zyrek, Magdalena

    2016-01-01

    In the last decade, drug resistant invasive mycoses have become significantly more common and new antifungal drugs and ways to specifically deliver them to the fungal cell are being looked for. One of the biggest obstacles in finding such comes from the fact that fungi share essential metabolic pathways with humans. One significant difference in the metabolism of those two cells that can be challenged when looking for possible selective therapeutics is the uptake of zinc, a nutrient crucial for the fungal survival and virulence. This work summarizes the recent advances in the biological inorganic chemistry of zinc metabolism in fungi. The regulation of zinc uptake, various types of its transmembrane transport, storage and the maintenance of intracellular zinc homeostasis is discussed in detail, with a special focus on the concept of a constant 'tug of war' over zinc between the fungus and its host, with the host trying to withhold essential Zn(II), and the fungus counteracting by producing high-affinity zinc binding molecules.

  5. Oxidative stress response to menadione and cumene hydroperoxide in the opportunistic fungal pathogen Candida glabrata

    Directory of Open Access Journals (Sweden)

    Mayra Cuéllar-Cruz

    2009-07-01

    Full Text Available Candida glabrata is an opportunistic fungal pathogen that can cause severe invasive infections and can evade phagocytic cell clearance. We are interested in understanding the virulence of this fungal pathogen, in particular its oxidative stress response. Here we investigated C. glabrata, Saccharomyces cerevisiae and Candida albicans responses to two different oxidants: menadione and cumene hydroperoxide (CHP. In log-phase, in the presence of menadione, C. glabrata requires Cta1p (catalase, while in a stationary phase (SP, Cta1p is dispensable. In addition, C. glabrata is less resistant to menadione than C. albicans in SP. The S. cerevisiae laboratory reference strain is less resistant to menadione than C. glabrata and C. albicans; however S. cerevisiaeclinical isolates (CIs are more resistant than the lab reference strain. Furthermore, S. cerevisiae CIs showed an increased catalase activity. Interestingly, in SP C. glabrata and S. cerevisiae are more resistant to CHP than C. albicans and Cta1p plays no apparent role in detoxifying this oxidant.

  6. Integrating chytrid fungal parasites into plankton ecology: research gaps and needs.

    Science.gov (United States)

    Frenken, Thijs; Alacid, Elisabet; Berger, Stella A; Bourne, Elizabeth C; Gerphagnon, Mélanie; Grossart, Hans-Peter; Gsell, Alena S; Ibelings, Bas W; Kagami, Maiko; Küpper, Frithjof C; Letcher, Peter M; Loyau, Adeline; Miki, Takeshi; Nejstgaard, Jens C; Rasconi, Serena; Reñé, Albert; Rohrlack, Thomas; Rojas-Jimenez, Keilor; Schmeller, Dirk S; Scholz, Bettina; Seto, Kensuke; Sime-Ngando, Télesphore; Sukenik, Assaf; Van de Waal, Dedmer B; Van den Wyngaert, Silke; Van Donk, Ellen; Wolinska, Justyna; Wurzbacher, Christian; Agha, Ramsy

    2017-10-01

    Chytridiomycota, often referred to as chytrids, can be virulent parasites with the potential to inflict mass mortalities on hosts, causing e.g. changes in phytoplankton size distributions and succession, and the delay or suppression of bloom events. Molecular environmental surveys have revealed an unexpectedly large diversity of chytrids across a wide range of aquatic ecosystems worldwide. As a result, scientific interest towards fungal parasites of phytoplankton has been gaining momentum in the past few years. Yet, we still know little about the ecology of chytrids, their life cycles, phylogeny, host specificity and range. Information on the contribution of chytrids to trophic interactions, as well as co-evolutionary feedbacks of fungal parasitism on host populations is also limited. This paper synthesizes ideas stressing the multifaceted biological relevance of phytoplankton chytridiomycosis, resulting from discussions among an international team of chytrid researchers. It presents our view on the most pressing research needs for promoting the integration of chytrid fungi into aquatic ecology. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  7. Expression of virulence factors by Staphylococcus aureus grown in serum.

    Science.gov (United States)

    Oogai, Yuichi; Matsuo, Miki; Hashimoto, Masahito; Kato, Fuminori; Sugai, Motoyuki; Komatsuzawa, Hitoshi

    2011-11-01

    Staphylococcus aureus produces many virulence factors, including toxins, immune-modulatory factors, and exoenzymes. Previous studies involving the analysis of virulence expression were mainly performed by in vitro experiments using bacterial medium. However, when S. aureus infects a host, the bacterial growth conditions are quite different from those in a medium, which may be related to the different expression of virulence factors in the host. In this study, we investigated the expression of virulence factors in S. aureus grown in calf serum. The expression of many virulence factors, including hemolysins, enterotoxins, proteases, and iron acquisition factors, was significantly increased compared with that in bacterial medium. In addition, the expression of RNA III, a global regulon for virulence expression, was significantly increased. This effect was partially restored by the addition of 300 μM FeCl₃ into serum, suggesting that iron depletion is associated with the increased expression of virulence factors in serum. In chemically defined medium without iron, a similar effect was observed. In a mutant with agr inactivated grown in serum, the expression of RNA III, psm, and sec4 was not increased, while other factors were still induced in the mutant, suggesting that another regulatory factor(s) is involved. In addition, we found that serum albumin is a major factor for the capture of free iron to prevent the supply of iron to bacteria grown in serum. These results indicate that S. aureus expresses virulence factors in adaptation to the host environment.

  8. Detection of virulence-associated genes in Brucella melitensis ...

    African Journals Online (AJOL)

    Ibrahim Eldaghayes

    2018-03-20

    Mar 20, 2018 ... isolated from goats. This discrepancies may indicate that B. melitensis field strains prevailing in Egypt are more virulent than the strains of B. melitensis isolated from caprines in Iran. As, it was emphasized that the. T4SS of Brucella encoded by the virB operon is a major virulence factor (Delrue et al., 2005).

  9. Limiting opportunities for cheating stabilizes virulence in insect parasitic nematodes

    Science.gov (United States)

    Cooperative secretion of virulence factors by pathogens can often lead to social conflict as cheating mutants that benefit from collective action, but do not contribute to it, can arise and locally outcompete cooperators within hosts, leading to loss of virulence. There is a wide range of in vivo st...

  10. Antibiotic Resistance and Virulence Properties in Escherichia coli ...

    African Journals Online (AJOL)

    This study determined E. coli resistance to commonly used antibiotics together with their virulence properties in Ile-Ife, Nigeria. A total of 137 E. coli isolates from cases of urinary tract infection were tested for their sensitivity to commonly used antibiotics and possession of virulence factors using standard methods.

  11. [Experimental-morphological study of morphogenetic potencies of homogeneous aggregates of different types of cells from the freshwater sponge Ephydatia fluviatilis (L.)].

    Science.gov (United States)

    Nikitin, N S

    1977-01-01

    The morphogenetic potencies of somatic cells of the fresh-water sponge Ephydatia fluviatilis in the developing aggregates depend on their initial specialization and the number of cells in the aggregate. The aggregates of nucleolar amoebocytes consisting of 500 or more cells have the highest morphogenetic potencies. All main cell types can arise in the developing homogeneous aggregates of nucleolar amoebocytes. The fine structure of nucleolar amoebocytes at different stages of development of the homogeneous aggregates was studied by means of electron microscopy. The structural rearrangements are described which accompany the process of redifferentiation of the nucleolar amoebocytes in other cell types.

  12. Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD.

    Science.gov (United States)

    White, Courtney L; Kitich, Aleksandar; Gober, James W

    2010-05-01

    In Caulobacter crescentus, intact cables of the actin homologue, MreB, are required for the proper spatial positioning of MurG which catalyses the final step in peptidoglycan precursor synthesis. Similarly, in the periplasm, MreC controls the spatial orientation of the penicillin binding proteins and a lytic transglycosylase. We have now found that MreB cables are required for the organization of several other cytosolic murein biosynthetic enzymes such as MraY, MurB, MurC, MurE and MurF. We also show these proteins adopt a subcellular pattern of localization comparable to MurG, suggesting the existence of cytoskeletal-dependent interactions. Through extensive two-hybrid analyses, we have now generated a comprehensive interaction map of components of the bacterial morphogenetic complex. In the cytosol, this complex contains both murein biosynthetic enzymes and morphogenetic proteins, including RodA, RodZ and MreD. We show that the integral membrane protein, MreD, is essential for lateral peptidoglycan synthesis, interacts with the precursor synthesizing enzymes MurG and MraY, and additionally, determines MreB localization. Our results suggest that the interdependent localization of MreB and MreD functions to spatially organize a complex of peptidoglycan precursor synthesis proteins, which is required for propagation of a uniform cell shape and catalytically efficient peptidoglycan synthesis.

  13. Packaging conditions hindering fungal growth on cheese

    DEFF Research Database (Denmark)

    Nielsen, Per Væggemose; Haasum, Iben

    1997-01-01

    Fungal contamination is one of the most important quality deteriorating factors on cheese. During the last 5 years we have studied in detail the underlying factors controlling these unwanted processes in a collaborative project financed by the Danish Dairy Board and the Ministry of Agriculture...

  14. Fungal peroxidases : molecular aspects and applications

    NARCIS (Netherlands)

    Conesa, A.; Punt, P.J.; Hondel, C.A.M.J.J.

    2002-01-01

    Peroxidases are oxidoreductases that utilize hydrogen peroxide to catalyze oxidative reactions. A large number of peroxidases have been identified in fungal species and are being characterized at the molecular level. In this manuscript we review the current knowledge on the molecular aspects of this

  15. Fungal Planet description sheets: 400-468

    Czech Academy of Sciences Publication Activity Database

    Crous, P.W.; Wingfield, M. J.; Richardson, D. M.; Le Roux, J. J.; Strasberg, D.; Edwards, J.; Roets, F.; Hubka, V.; Taylor, P.W.J.; Heykoop, M.; Martín, M.P.; Moreno, G.; Sutton, D.A.; Wiederhold, N.P.; Barnes, C.W.; Carlavilla, J.R.; Gené, J.; Giraldo, A.; Guarnaccia, V.; Guarro, J.; Hernández-Restrepo, M.; Kolařík, Miroslav; Manjón, J.L.; Pascoe, I.G.; Popov, E.S.; Sandoval-Denis, M.; Woudenberg, J.H.C.; Acharya, K.; Alexandrova, A.V.; Alvarado, P.; Barbosa, R.N.; Baseia, I.G.; Blanchette, R.A.; Boekhout, T.; Burgess, T.I.; Cano-Lira, J.F.; Čmoková, A.; Dimitrov, R.A.; Dyakov, M.Yu.; Dueñas, M.; Dutta, A.K.; Esteve- Raventós, F.; Fedosova, A.G.; Fournier, J.; Gamboa, P.; Gouliamova, D.E.; Grebenc, T.; Groenewald, M.; Hanse, B.; Hardy, G.E.St.J.; Held, B.W.; Jurjević, Ž.; Kaewgrajang, T.; Latha, K.P.D.; Lombard, L.; Luangsa-Ard, J.J.; Lysková, P.; Mallátová, N.; Manimohan, P.; Miller, A.N.; Mirabolfathy, M.; Morozova, O.V.; Obodai, M.; Oliveira, N.T.; Otto, E.C.; Paloi, S.; Peterson, S.W.; Phosri, C.; Roux, J.; Salazar, W.A.; Sánchez, A.; Sarria, G.A.; Shin, H.-D.; Silva, B.D.B.; Silva, G.A.; Smith, M.Th.; Souza-Motta, C.M.; Stchigel, A.M.; Stoilova-Disheva, M.M.; Sulzbacher, M.A.; Telleria, M.T.; Toapanta, C.; Traba, J.M.; Valenzuela-Lopez, N.; Watling, R.; Groenewald, J.Z.

    2016-01-01

    Roč. 36, July (2016), s. 316-458 ISSN 0031-5850 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : ITS DNA barcodes * LSU * fungal species Subject RIV: EE - Microbiology, Virology Impact factor: 7.511, year: 2016

  16. A biotechnology perspective of fungal proteases

    Directory of Open Access Journals (Sweden)

    Paula Monteiro de Souza

    2015-06-01

    Full Text Available Proteases hydrolyze the peptide bonds of proteins into peptides and amino acids, being found in all living organisms, and are essential for cell growth and differentiation. Proteolytic enzymes have potential application in a wide number of industrial processes such as food, laundry detergent and pharmaceutical. Proteases from microbial sources have dominated applications in industrial sectors. Fungal proteases are used for hydrolyzing protein and other components of soy beans and wheat in soy sauce production. Proteases can be produced in large quantities in a short time by established methods of fermentation. The parameters such as variation in C/N ratio, presence of some sugars, besides several other physical factors are important in the development of fermentation process. Proteases of fungal origin can be produced cost effectively, have an advantage faster production, the ease with which the enzymes can be modified and mycelium can be easily removed by filtration. The production of proteases has been carried out using submerged fermentation, but conditions in solid state fermentation lead to several potential advantages for the production of fungal enzymes. This review focuses on the production of fungal proteases, their distribution, structural-functional aspects, physical and chemical parameters, and the use of these enzymes in industrial applications.

  17. High prevalence of a fungal prion

    NARCIS (Netherlands)

    Debets, A.J.M.; Dalstra, H.J.P.; Slakhorst, S.M.; Koopmanschap-Memelink, A.B.; Hoekstra, R.F.; Saupe, S.J.

    2012-01-01

    Prions are infectious proteins that cause fatal diseases in mammals. Prions have also been found in fungi, but studies on their role in nature are scarce. The proposed biological function of fungal prions is debated and varies from detrimental to benign or even beneficial. [Het-s] is a prion of the

  18. October 2012 Multistate Fungal Meningitis Outbreak

    Centers for Disease Control (CDC) Podcasts

    2012-10-17

    This podcast gives an overview of the October 2012 multistate fungal meningitis outbreak, including symptoms to watch for and a website for up-to-date information.  Created: 10/17/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/17/2012.

  19. Fungal biology and agriculture: revisiting the field

    Science.gov (United States)

    Yarden, O.; Ebbole, D.J.; Freeman, S.; Rodriguez, R.J.; Dickman, M. B.

    2003-01-01

    Plant pathology has made significant progress over the years, a process that involved overcoming a variety of conceptual and technological hurdles. Descriptive mycology and the advent of chemical plant-disease management have been followed by biochemical and physiological studies of fungi and their hosts. The later establishment of biochemical genetics along with the introduction of DNA-mediated transformation have set the stage for dissection of gene function and advances in our understanding of fungal cell biology and plant-fungus interactions. Currently, with the advent of high-throughput technologies, we have the capacity to acquire vast data sets that have direct relevance to the numerous subdisciplines within fungal biology and pathology. These data provide unique opportunities for basic research and for engineering solutions to important agricultural problems. However, we also are faced with the challenge of data organization and mining to analyze the relationships between fungal and plant genomes and to elucidate the physiological function of pertinent DNA sequences. We present our perspective of fungal biology and agriculture, including administrative and political challenges to plant protection research.

  20. Fungal Systematics and Evolution: FUSE 1

    NARCIS (Netherlands)

    Crous, Pedro W; Schumacher, René K; Wingfield, Michael J; Lombard, Lorenzo; Giraldo, Alejandra; Christensen, Martha; Gardiennet, Alain; Nakashima, Chiharu; Pereira, Olinto L; Smith, Alexander J; Groenewald, Johannes Z

    2015-01-01

    Fungal Systematics and Evolution (FUSE) is introduced as a new series to expedite the publication of issues relating to the epitypification of formerly described species, report new sexual-asexual connections, the merging of sexual and asexual gen¬era following the end of dual nomenclature, and to

  1. Fungal Planet description sheets: 371-399

    Czech Academy of Sciences Publication Activity Database

    Crous, P. W.; Wingfield, M. J.; Le Roux, J. J.; Richardson, D. M.; Strasberg, D.; Shivas, R.G.; Alvarado, P.; Edwards, J.; Moreno, G.; Sharma, R.; Sonawane, M.S.; Tan, Y.P.; Altés, A.; Barasubiye, T.; Barnes, C.W.; Blanchette, R.A.; Boertmann, D.; Bogo, A.; Carlavilla, J.R.; Cheewangkoon, R.; Daniel, R.; de Beer, Z.W.; de Yáňez-Morales, J.; Duong, T.A.; Fernández-Vicente, J.; Geering, A.D.W.; Guest, D.I.; Held, B.W.; Heykoop, M.; Hubka, V.; Ismail, A.M.; Kajale, S.C.; Khemmuk, W.; Kolařík, Miroslav; Kurli, R.; Lebeuf, R.; Levesque, C.A.; Lombard, L.; Magista, D.; Manjón, J.L.; Marincowitz, S.; Mohedano, J.M.; Nováková, Alena; Oberlies, N.H.; Otto, E.C.; Paguigan, N.D.; Pascoe, I.G.; Peréz-Butrón, J.L.; Perrone, G.; Rahi, P.; Raja, H.A.; Rintoul, T.; Sanhueza, R.M.V.; Scarlett, K.; Shouche, Y.S.; Shuttleworth, L.A.; Taylor, P.W.J.; Thorn, R.G.; Vawdrey, L.L.; Solano-Vidal, R.; Voitk, A.; Wong, P.T.W.; Wood, A.R.; Zamora, J.C.; Groenewald, J.Z.

    2015-01-01

    Roč. 35, December (2015), s. 264-327 ISSN 0031-5850 R&D Projects: GA ČR(CZ) GAP506/12/1064 Institutional support: RVO:61388971 Keywords : ITS DNA barcodes * LSU * novel fungal species Subject RIV: EE - Microbiology, Virology Impact factor: 5.725, year: 2015

  2. Fungal ABC Transporter Deletion and Localization Analysis

    NARCIS (Netherlands)

    Kovalchuk, A.; Weber, S.S.; Nijland, J.G.; Bovenberg, R.A.L.; Driessen, A.J.M.

    2012-01-01

    Fungal cells are highly complex as their metabolism is compartmentalized harboring various types of subcellular organelles that are bordered by one or more membranes. Knowledge about the intracellular localization of transporter proteins is often required for the understanding of their biological

  3. CT scan findings of fungal pneumonia

    International Nuclear Information System (INIS)

    Heckmann, M.; Uder, M.; Bautz, W.; Heinrich, M.

    2008-01-01

    The importance of fungal infection of the lung in immunocompromised patients has increased substantially during the last decades. Numerically the most patients are those with neutropenia, e.g. patients with malignancies or solid organ and stem cell transplantation, chemotherapy, corticosteroid use and HIV infection. Although fungal infections can occur in immunocompetent patients, their frequency in this population is rare. The clinical symptoms such as fever accompanied with non-productive cough are unspecific. In some patients progression to hypoxemia and dyspnea may occur rapidly. In spite of improved antifungal therapy morbidity and mortality of these infections are still high. Therefore an early and non-invasive diagnosis is very important. That is why CT and even better High-Resolution-CT (HR-CT) is a very important modality in examining immunocompromised patients with a probability of fungal infection. CT is everywhere available and, as a non-invasive method, able to give the relevant diagnose efficiently. This paper should give an overview about the radiologic findings and possible differential diagnosis of diverse pulmonary fungal infections in CT. Pneumonias caused by Aspergillus, Cryptococcus, Candida, Histoplasma, Mucor and Geotrichum capitatum are illustrated. (orig.)

  4. The Amstersam declaration on fungal nomenclature

    DEFF Research Database (Denmark)

    Hawksworth, David L.; Crous, Pedro W.; Redhead, Scott A.

    2011-01-01

    The Amsterdam Declaration on Fungal Nomenclature was agreed at an international symposium convened in Amsterdam on 19–20 April 2011 under the auspices of the International Commission on the Taxonomy of Fungi (ICTF). The purpose of the symposium was to address the issue of whether or how the current...

  5. Fungal peritonitis in children on peritoneal dialysis.

    NARCIS (Netherlands)

    Raaijmakers, R.; Schroder, C.; Monnens, L.A.H.; Cornelissen, E.A.M.; Warris, A.

    2007-01-01

    Fungal peritonitis is a rare but serious complication in children on peritoneal dialysis (PD). In this study, risk factors were evaluated, and therapeutic measures were reviewed. A retrospective, multi-centre study was performed in 159 Dutch paediatric PD patients, between 1980 and 2005 (3,573

  6. UV-guided isolation of fungal metabolites by HSCCC

    DEFF Research Database (Denmark)

    Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

    2005-01-01

    Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series...... peptides from a crude fungal extract....

  7. Burden of Serious Fungal Infections in Jordan

    Directory of Open Access Journals (Sweden)

    Jamal Wadi

    2018-01-01

    Full Text Available Objective: To estimate the burden of fungal infections in Jordan for the first time. Material and Methods: Population data was from UN 2011 statistics and TB cases from WHO in 2012. Fewer than 100 patients with HIV were recorded in Jordan in 2013. Approximately 100 renal transplants and eight liver transplants are performed annually. There were 12,233 major surgical procedures in Jordan in 2013, of which 5.3% were major abdominal surgeries; candidemia was estimated in 5% of the population based on other countries, with 33% occurring in the ICU. Candida peritonitis/intra-abdominal candidiasis was estimated to affect 50% of the number of ICU candidemia cases. No adult asthma rates have been recorded for Jordan, so the rate from the Holy Land (8.54% clinical asthma from To et al. has been used. There are an estimated 49,607 chronic obstructive pulmonary disease (COPD patients in Jordan, with 64% symptomatic, 25% Gold stage 3% or 4%, and 7% (3472 are assumed to be admitted to hospital each year. No cystic fibrosis cases have been recorded. Literature searches on fungal infections revealed few data and no prevalence data on fungal keratitis or tinea capitis, even though tinea capitis comprised 34% of patients with dermatophytoses in Jordan. Results: Jordan has 6.3 million inhabitants (65% adults, 6% are >60 years old. The current burden of serious fungal infections in Jordan was estimated to affect ~119,000 patients (1.9%, not including any cutaneous fungal infections. Candidemia was estimated at 316 cases and invasive aspergillosis in leukemia, transplant, and COPD patients at 84 cases. Chronic pulmonary aspergillosis prevalence was estimated to affect 36 post-TB patients, and 175 in total. Allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS prevalence in adults with asthma were estimated at 8900 and 11,748 patients. Recurrent vulvovaginal candidiasis was estimated to affect 97,804 patients, using a 6

  8. Effects of bone morphogenetic protein-2 on bone cells in primary culture: immunohistochemical and electronmicroscopical studies

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, I.; Prochnow, N.; Mueller, K.M. [Berufsgenossenschaftliche Kliniken Bergmannsheil, Bochum (Germany). Inst. fuer Pathologie; Wiemann, M.; Schirrmacher, K.; Bingmann, D. [Essen Univ. (Germany). Inst. fuer Physiologie; Sebald, W. [Wuerzburg Univ. (Germany). Inst. fuer Physiologische Chemie II

    2001-02-01

    Bone morphogenetic protein 2 (BMP-2), among other morphogenetic effects on non osseous tissues, promotes bone formation in vivo. Therefore, BMP-2 may accelerate the integration of osseous implants. Although the effects of BMPs on cell proliferation have been studied extensively in vivo or in cell lines, little is published about effects on bone cells in primary cultures, especially on cell differentiation. As such information is a prerequisite to understand and to control effects of BMPs on cells at the surface of implant materials, the present experiments aimed to describe effects of BMP-2 on primary cultures derived from calvarial fragments of neonatal rats. The cells were stimulated with 50 nM BMP-2 added to the nutrient medium for 3 or 6 days. Light- and electronmicroscopical studies showed that cells in the sprouting zones were larger and more often spindle shaped. Stimulated cells had more nucleoli than control cells and the endoplasmic reticulum was widened. They retained properties of typical bone cells: An immunhistochemical analysis showed that stimulated cells increased the activity of alkaline phosphatase, they secreted collagen type I and to a minor extent collagen type III. In BMP-2 treated cells the pattern of cells stained for actin, desmin and vimentin hardly changed whereas extracellular fibronectin appeared to be less cross-linked in BMP-2 treated cultures. The distribution and labeling strength of osteocalcin, a specific marker protein of bone cells did not change markedly. After exposure to BMP-2 cells tended to detach from the cover slips. Electron microscopy showed a reduced number of cell processes possibly facilitating the detachment and/or mobility. Stimulated cells contained an increased number of lamellar bodies which may reflect an increased synthesis and/or membrane turnover. Staining of non-osseous cells with anti-CD68-or anti-myeloid antibodies revealed that the small percentage of these cells regularly occurring in primary cultures

  9. Transcriptome analysis of the honey bee fungal pathogen, Ascosphaera apis: implications for host pathogenesis

    Directory of Open Access Journals (Sweden)

    Cornman R

    2012-06-01

    Full Text Available Abstract Background We present a comprehensive transcriptome analysis of the fungus Ascosphaera apis, an economically important pathogen of the Western honey bee (Apis mellifera that causes chalkbrood disease. Our goals were to further annotate the A. apis reference genome and to identify genes that are candidates for being differentially expressed during host infection versus axenic culture. Results We compared A. apis transcriptome sequence from mycelia grown on liquid or solid media with that dissected from host-infected tissue. 454 pyrosequencing provided 252 Mb of filtered sequence reads from both culture types that were assembled into 10,087 contigs. Transcript contigs, protein sequences from multiple fungal species, and ab initio gene predictions were included as evidence sources in the Maker gene prediction pipeline, resulting in 6,992 consensus gene models. A phylogeny based on 12 of these protein-coding loci further supported the taxonomic placement of Ascosphaera as sister to the core Onygenales. Several common protein domains were less abundant in A. apis compared with related ascomycete genomes, particularly cytochrome p450 and protein kinase domains. A novel gene family was identified that has expanded in some ascomycete lineages, but not others. We manually annotated genes with homologs in other fungal genomes that have known relevance to fungal virulence and life history. Functional categories of interest included genes involved in mating-type specification, intracellular signal transduction, and stress response. Computational and manual annotations have been made publicly available on the Bee Pests and Pathogens website. Conclusions This comprehensive transcriptome analysis substantially enhances our understanding of the A. apis genome and its expression during infection of honey bee larvae. It also provides resources for future molecular studies of chalkbrood disease and ultimately improved disease management.

  10. Transcriptome analysis of the honey bee fungal pathogen, Ascosphaera apis: implications for host pathogenesis

    Science.gov (United States)

    2012-01-01

    Background We present a comprehensive transcriptome analysis of the fungus Ascosphaera apis, an economically important pathogen of the Western honey bee (Apis mellifera) that causes chalkbrood disease. Our goals were to further annotate the A. apis reference genome and to identify genes that are candidates for being differentially expressed during host infection versus axenic culture. Results We compared A. apis transcriptome sequence from mycelia grown on liquid or solid media with that dissected from host-infected tissue. 454 pyrosequencing provided 252 Mb of filtered sequence reads from both culture types that were assembled into 10,087 contigs. Transcript contigs, protein sequences from multiple fungal species, and ab initio gene predictions were included as evidence sources in the Maker gene prediction pipeline, resulting in 6,992 consensus gene models. A phylogeny based on 12 of these protein-coding loci further supported the taxonomic placement of Ascosphaera as sister to the core Onygenales. Several common protein domains were less abundant in A. apis compared with related ascomycete genomes, particularly cytochrome p450 and protein kinase domains. A novel gene family was identified that has expanded in some ascomycete lineages, but not others. We manually annotated genes with homologs in other fungal genomes that have known relevance to fungal virulence and life history. Functional categories of interest included genes involved in mating-type specification, intracellular signal transduction, and stress response. Computational and manual annotations have been made publicly available on the Bee Pests and Pathogens website. Conclusions This comprehensive transcriptome analysis substantially enhances our understanding of the A. apis genome and its expression during infection of honey bee larvae. It also provides resources for future molecular studies of chalkbrood disease and ultimately improved disease management. PMID:22747707

  11. Presentation and management of allergic fungal sinusitis

    International Nuclear Information System (INIS)

    Thahim, K.; Jawaid, M.A.; Marfani, S.

    2007-01-01

    To assess the presentation of allergic fungal sinusitis and describe the line of management in our setup. Culture and sensitivity / fungal stain proven 20 cases of allergic fungal sinusitis were selected for the study, irrespective of age and gender. Data including age, gender, socioeconomic status, signs, symptoms, laboratory findings (especially Immunoglobulin E and eosinophil count) and imaging studies (Computed Tomography and /or Magnetic Resonance Imaging) were noted for the study. Pre and postoperative medical treatment, surgery performed, follow-up; residual/recurrence disease and revised surgery performed were also recorded. In this series, allergic fungal sinusitis was a disease of younger age group with an average age of 20.75 years with male dominance (70%). Poor socioeconomic status (80%), allergic rhinitis (100%) and nasal polyposis (100%) were important associated factors. Nasal obstruction (100%), nasal discharge (90%), postnasal drip (90%) and unilateral nasal and paranasal sinuses involvement (60%) were the commonest presenting features. Aspergillus (60%) was the most common etiological agent. In all cases (100%), increased eosinophil count and IgE levels were present. Orbital (20%) and intracranial (10%) involvement were also seen. Surgical management was preferred in all cases. Functional endoscopic sinus surgery in 90% cases and lateral rhinotomy in 10% cases were performed. Recurrence / residual disease was seen in 20% cases. In this series, allergic fungal sinusitis was seen in immunocompetent, young males, belonging to poor socioeconomic status, suffering from allergic rhinitis and nasal polyposis, presenting with nasal obstruction, nasal discharge and postnasal drip. Functional endoscopic sinus surgery was the most important problem solving procedure while lateral rhinotomy was reserved for extensive disease. (author)

  12. Fungal endophytes which invade insect galls: insect pathogens, benign saprophytes, or fungal inquilines?

    Science.gov (United States)

    Wilson, Dennis

    1995-08-01

    Fungi are frequently found within insect galls. However, the origin of these fungi, whether they are acting as pathogens, saprophytes invading already dead galls, or fungal inquilines which invade the gall but kill the gall maker by indirect means, is rarely investigated. A pathogenic role for these fungi is usually inferred but never tested. I chose the following leaf-galling-insect/host-plant pairs (1) a cynipid which forms two-chambered galls on the veins of Oregon white oak, (2) a cynipid which forms single-chambered galls on California coast live oak, and (3) an aphid which forms galls on narrowleaf cottonwood leaves. All pairs were reported to have fungi associated with dead insects inside the gall. These fungi were cultured and identified. For the two cynipids, all fungi found inside the galls were also present in the leaves as fungal endophytes. The cottonwood leaves examined did not harbor fungal endophytes. For the cynipid on Oregon white oak, the fungal endophyte grows from the leaf into the gall and infects all gall tissue but does not directly kill the gall maker. The insect dies as a result of the gall tissue dying from fungal infection. Therefore, the fungus acts as an inquiline. Approximately 12.5% of these galls die as a result of invasion by the fungal endophyte.

  13. The Central Metabolism Regulator EIIAGlc Switches Salmonella from Growth Arrest to Acute Virulence through Activation of Virulence Factor Secretion

    Directory of Open Access Journals (Sweden)

    Alain Mazé

    2014-06-01

    Full Text Available The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2 involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism.

  14. Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis.

    Science.gov (United States)

    Kumar, Rohitashw; Saraswat, Darpan; Tati, Swetha; Edgerton, Mira

    2015-07-01

    Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Δsap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Δsap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

  15. Fungal polyketide azaphilone pigments as future natural food colorants?

    DEFF Research Database (Denmark)

    Mapari, Sameer Shamsuddin; Thrane, Ulf; Meyer, Anne S.

    2010-01-01

    The recent approval of fungal carotenoids as food colorants by the European Union has strengthened the prospects for fungal cell factories for the production of polyketide pigments. Fungal production of colorants has the main advantage of making the manufacturer independent of the seasonal supply...... functionality and to expand the color palette of contemporary natural food colorants.......The recent approval of fungal carotenoids as food colorants by the European Union has strengthened the prospects for fungal cell factories for the production of polyketide pigments. Fungal production of colorants has the main advantage of making the manufacturer independent of the seasonal supply...... of raw materials, thus minimizing batch-to-batch variations. Here, we review the potential of polyketide pigments produced from chemotaxonomically selected non-toxigenic fungal strains (e.g. Penicillium and Epicoccum spp.) to serve as food colorants. We argue that the production of polyketide azaphilone...

  16. Fungal atopy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    Henry, M

    2012-02-03

    This study set out to estimate the prevalence of atopy to a variety of common ubiquitous fungi, including A. fumigatus, in cystic fibrosis (CF), and to evaluate the investigations by which the diagnosis was made. Particular attention was paid to the usefulness of skin testing and immunoassays in detecting which patients had simple fungal atopy, and which patients were at high risk of developing allergic bronchopulmonary mycoses. This cross-sectional study included 21 adult CF patients and 20 matched controls. Serum samples were taken for the measurement of total serum IgE and specific serum IgE to nine common fungi. Immediate hypersensitivity skin prick testing to each of the fungi was also performed. Simple fungal atopy was described in subjects fulfilling the following criteria: total serum IgE > 100 KU l(-1) with specific radioimmunoassay > or = grade 1 to at least one fungus and a positive skin prick test (SPT) > or = 3 mm to the same fungus. \\'High risk\\' for developing allergic bronchopulmonary mycosis (ABPM) was described in subjects fulfilling the following criteria: total serum IgE > 200 KU l(-1) with specific radioimmunoassay > or = grade 2 to at least one fungus and a positive skin prick test (SPT) > or = 6 mm to the same fungus. The adult CF group had a significantly higher total SPT score (P=0.005) and mean total serum IgE (P<0.05) than controls. Forty-three percent of CF patients fulfilled the criteria for fungal atopy to at least a single fungus. Over half this group had an atopic tendency to more than one fungus. Nineteen percent of the CF group were at least \\'high risk\\' of developing ABPM. Skin prick testing is a better marker of fungal atopy and a better predictor of those adult CF patients at higher risk of developing ABPM than specific radioimmunoassay serum testing. There is a high prevalence of fungal atopy in the adult CF population. Total serum IgE and skin prick testing are good predictors of fungal atopy and help predict those at

  17. Symbiotic fungal associations in 'lower' land plants.

    Science.gov (United States)

    Read, D J; Ducket, J G; Francis, R; Ligron, R; Russell, A

    2000-06-29

    An analysis of the current state of knowledge of symbiotic fungal associations in 'lower' plants is provided. Three fungal phyla, the Zygomycota, Ascomycota and Basidiomycota, are involved in forming these associations, each producing a distinctive suite of structural features in well-defined groups of 'lower' plants. Among the 'lower' plants only mosses and Equisetum appear to lack one or other of these types of association. The salient features of the symbioses produced by each fungal group are described and the relationships between these associations and those formed by the same or related fungi in 'higher' plants are discussed. Particular consideration is given to the question of the extent to which root fungus associations in 'lower' plants are analogous to 'mycorrhizas' of 'higher' plants and the need for analysis of the functional attributes of these symbioses is stressed. Zygomycetous fungi colonize a wide range of extant lower land plants (hornworts, many hepatics, lycopods, Ophioglossales, Psilotales and Gleicheniaceae), where they often produce structures analogous to those seen in the vesicular-arbuscular (VA) mycorrhizas of higher plants, which are formed by members of the order Glomales. A preponderance of associations of this kind is in accordance with palaeohbotanical and molecular evidence indicating that glomalean fungi produced the archetypal symbioses with the first plants to emerge on to land. It is shown, probably for the first time, that glomalean fungi forming typical VA mycorrhiza with a higher plant (Plantago lanceolata) can colonize a thalloid liverwort (Pellia epiphylla), producing arbuscules and vesicles in the hepatic. The extent to which these associations, which are structurally analogous to mycorrhizas, have similar functions remains to be evaluated. Ascomycetous associations are found in a relatively small number of families of leafy liverworts. The structural features of the fungal colonization of rhizoids and underground axes of

  18. Transplant tourism and invasive fungal infection

    Directory of Open Access Journals (Sweden)

    I. Al Salmi

    2018-04-01

    Full Text Available Background: Deceased and live-related renal transplants (RTXs are approved procedures that are performed widely throughout the world. In certain regions, commercial RTX has become popular, driven by financial greed. Methods: This retrospective, descriptive study was performed at the Royal Hospital from 2013 to 2015. Data were collected from the national kidney transplant registry of Oman. All transplant cases retrieved were divided into two groups: live-related RTX performed in Oman and commercial-unrelated RTX performed abroad. These groups were then divided again into those with and without evidence of fungal infection, either in the wound or renal graft. Results: A total of 198 RTX patients were identified, of whom 162 (81.8% had undergone a commercial RTX that was done abroad. Invasive fungal infections (IFIs were diagnosed in 8% of patients who had undergone a commercial RTX; of these patients, 76.9% underwent a nephrectomy and 23.1% continued with a functioning graft. None of the patients with RTXs performed at the Royal Hospital contracted an IFI. The most common fungal isolates were Aspergillus species (including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, and Aspergillus nigricans, followed by Zygomycetes. However, there was no evidence of fungal infection including Aspergillus outside the graft site. Computed tomography (CT findings showed infarction of the graft, renal artery thrombosis, aneurysmal dilatation of the external iliac artery, fungal ball, or just the presence of a perigraft collection. Of the total patients with IFIs, 23.1% died due to septic shock and 53.8% were alive and on hemodialysis. The remaining 23.1% who did not undergo nephrectomy demonstrated acceptable graft function. Conclusions: This is the largest single-center study on commercial RTX reporting the highest number of patients with IFI acquired over a relatively short period of time. Aspergillus spp were the main culprit fungi, with no

  19. Virulence evolution at the front line of spreading epidemics.

    Science.gov (United States)

    Griette, Quentin; Raoul, Gaël; Gandon, Sylvain

    2015-11-01

    Understanding and predicting the spatial spread of emerging pathogens is a major challenge for the public health management of infectious diseases. Theoretical epidemiology shows that the speed of an epidemic is governed by the life-history characteristics of the pathogen and its ability to disperse. Rapid evolution of these traits during the invasion may thus affect the speed of epidemics. Here we study the influence of virulence evolution on the spatial spread of an epidemic. At the edge of the invasion front, we show that more virulent and transmissible genotypes are expected to win the competition with other pathogens. Behind the front line, however, more prudent exploitation strategies outcompete virulent pathogens. Crucially, even when the presence of the virulent mutant is limited to the edge of the front, the invasion speed can be dramatically altered by pathogen evolution. We support our analysis with individual-based simulations and we discuss the additional effects of demographic stochasticity taking place at the front line on virulence evolution. We confirm that an increase of virulence can occur at the front, but only if the carrying capacity of the invading pathogen is large enough. These results are discussed in the light of recent empirical studies examining virulence evolution at the edge of spreading epidemics. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  20. Invasion thresholds and the evolution of nonequilibrium virulence.

    Science.gov (United States)

    Bull, James J; Ebert, Dieter

    2008-02-01

    The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonoptimal virulence. Fitness improvements soon after invasion may proceed through many steps with wide changes in virulence, because fitness depends on transmission as well as virulence, and transmission improvements can overwhelm nonoptimal virulence. This process is highly sensitive to mutation supply and the strength of selection. Importantly, the same invasion principle applies to the evolution of established parasites, whenever mutants arise that overcome host immunity/resistance. A host population may consequently experience repeated invasions of new parasite variants and possible large shifts in virulence as it evolves in an arms race with the parasite. An experimental study of phage lysis time and examples of mammalian viruses matching some of these characteristics are reviewed.

  1. Toxin-independent virulence of Bacillus anthracis in rabbits.

    Directory of Open Access Journals (Sweden)

    Haim Levy

    Full Text Available The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play a major role in pathogenicity. In the guinea pig (GP model we have previously shown that deletion of all three toxin components results in a relatively moderate attenuation in virulence, indicating that B. anthracis possesses an additional toxin-independent virulence mechanism. To characterize this toxin-independent mechanism in anthrax disease, we developed a new rabbit model by intravenous injection (IV of B. anthracis encapsulated vegetative cells, artificially creating bacteremia. Using this model we were able to demonstrate that also in rabbits, B. anthracis mutants lacking the toxins are capable of killing the host within 24 hours. This virulent trait depends on the activity of AtxA in the presence of pXO2, as, in the absence of the toxin genes, deletion of either component abolishes virulence. Furthermore, this IV virulence depends mainly on AtxA rather than the whole pXO1. A similar pattern was shown in the GP model using subcutaneous (SC administration of spores of the mutant strains, demonstrating the generality of the phenomenon. The virulent strains showed higher bacteremia levels and more efficient tissue dissemination; however our interpretation is that tissue dissemination per se is not the main determinant of virulence whose exact nature requires further elucidation.

  2. Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents

    DEFF Research Database (Denmark)

    Christensen, Gitte L.; Jacobsen, Maria L. B.; Wendt, Anna

    2015-01-01

    AIMS/HYPOTHESIS: Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression...

  3. STRO-1 selected rat dental pulp stem cells transfected with adenoviral-mediated human bone morphogenetic protein 2 gene show enhanced odontogenic differentiation.

    NARCIS (Netherlands)

    Yang, X.; Kraan, P.M. van der; Dolder, J. van den; Walboomers, X.F.; Bian, Z.; Fan, M.; Jansen, J.A.

    2007-01-01

    Dental pulp stem cells harbor great potential for tissue-engineering purposes. However, previous studies have shown variable results, and some have reported only limited osteogenic and odontogenic potential.Because bone morphogenetic proteins (BMPs) are well-established agents to induce bone and

  4. Coat Protein Mutations That Alter the Flux of Morphogenetic Intermediates through the ϕX174 Early Assembly Pathway.

    Science.gov (United States)

    Blackburn, Brody J; Li, Shuaizhi; Roznowski, Aaron P; Perez, Alexis R; Villarreal, Rodrigo H; Johnson, Curtis J; Hardy, Margaret; Tuckerman, Edward C; Burch, April D; Fane, Bentley A

    2017-12-15

    Two scaffolding proteins orchestrate ϕX174 morphogenesis. The internal scaffolding protein B mediates the formation of pentameric assembly intermediates, whereas the external scaffolding protein D organizes 12 of these intermediates into procapsids. Aromatic amino acid side chains mediate most coat-internal scaffolding protein interactions. One residue in the internal scaffolding protein and three in the coat protein constitute the core of the B protein binding cleft. The three coat gene codons were randomized separately to ascertain the chemical requirements of the encoded amino acids and the morphogenetic consequences of mutation. The resulting mutants exhibited a wide range of recessive phenotypes, which could generally be explained within a structural context. Mutants with phenylalanine, tyrosine, and methionine substitutions were phenotypically indistinguishable from the wild type. However, tryptophan substitutions were detrimental at two sites. Charged residues were poorly tolerated, conferring extreme temperature-sensitive and lethal phenotypes. Eighteen lethal and conditional lethal mutants were genetically and biochemically characterized. The primary defect associated with the missense substitutions ranged from inefficient internal scaffolding protein B binding to faulty procapsid elongation reactions mediated by external scaffolding protein D. Elevating B protein concentrations above wild-type levels via exogenous, cloned-gene expression compensated for inefficient B protein binding, as did suppressing mutations within gene B. Similarly, elevating D protein concentrations above wild-type levels or compensatory mutations within gene D suppressed faulty elongation. Some of the parental mutations were pleiotropic, affecting multiple morphogenetic reactions. This progressively reduced the flux of intermediates through the pathway. Accordingly, multiple mechanisms, which may be unrelated, could restore viability. IMPORTANCE Genetic analyses have been

  5. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, J.; Saunders, C.; Hu, P.; Grant, R.A.; Boekhout, T.; Kuramae, E.E.; Kronstad, J.W.; DeAngelis, Y.M.; Reeder, N.L.; Johnstone, K.R.; Leland, M.; Fieno, A.M.; Begley, W.M.; Sun, Y.; Lacey, M.P.; Chaudhary, T.; Keough, T.; Chu, L.; Sears, R.; Yuan, B.; Dawson Jr., T.L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  6. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect > 50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  7. Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence

    Directory of Open Access Journals (Sweden)

    María J. Navarro-Arias

    2016-12-01

    Full Text Available The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite there was a significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1 null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with

  8. Pseudogymnoascus destructans: evidence of virulent skin invasion for bats under natural conditions, Europe.

    Science.gov (United States)

    Bandouchova, H; Bartonicka, T; Berkova, H; Brichta, J; Cerny, J; Kovacova, V; Kolarik, M; Köllner, B; Kulich, P; Martínková, N; Rehak, Z; Turner, G G; Zukal, J; Pikula, J

    2015-02-01

    While Pseudogymnoascus destructans has been responsible for mass bat mortalities from white-nose syndrome (WNS) in North America, its virulence in Europe has been questioned. To shed the light on the issue of host-pathogen interaction between European bats and P. destructans, we examined seventeen bats emerging from the fungus-positive underground hibernacula in the Czech Republic during early spring 2013. Dual wing-membrane biopsies were taken from Barbastella barbastellus (1), Myotis daubentonii (1), Myotis emarginatus (1), Myotis myotis (11), Myotis nattereri (1) and Plecotus auritus (2) for standard histopathology and transmission electron microscopy. Non-lethal collection of suspected WNS lesions was guided by trans-illumination of the wing membranes with ultraviolet light. All bats selected for the present study were PCR-positive for P. destructans and showed microscopic findings consistent with the histopathological criteria for WNS diagnosis. Ultramicroscopy revealed oedema of the connective tissue and derangement of the fibroblasts and elastic fibres associated with skin invasion by P. destructans. Extensive fungal infection induced a marked inflammatory infiltration by neutrophils at the interface between the damaged part of the wing membrane replaced by the fungus and membrane tissue not yet invaded by the pathogen. There was no sign of keratinolytic activity in the stratum corneum. Here, we show that lesions pathognomonic for WNS are common in European bats and may also include overwhelming full-thickness fungal growth through the wing membrane equal in severity to reports from North America. Inter-continental differences in the outcome of WNS in bats in terms of morbidity/mortality may therefore not be due to differences in the pathogen itself. © 2014 Blackwell Verlag GmbH.

  9. Phenolic composition and medicinal usage of Psidium guajava Linn.: Antifungal activity or inhibition of virulence?

    Directory of Open Access Journals (Sweden)

    Maria F.B. Morais-Braga

    2017-02-01

    Full Text Available Psidium guajava is a Myrtaceae plant whose medicinal properties are recognized in several locations. The use of teas and tinctures prepared from their leaves has been used to combat infections caused by fungi of the genus Candida. In this study, aqueous extracts of leaves and hydroethanolic were tested to verify the antifungal potential and its chemical composition has been investigated. The microbiological assays were performed by broth microdilution to determine the minimum inhibitory concentration (MIC and from these the minimum fungicidal concentration was performed (MFC by subculturing on solid media. A cell viability curve was obtained for demonstration of inhibition of fungal growth of strains of Candida albicans and Candida tropicalis. Tests to check morphological changes by the action of the extracts were performed in microcultive cameras depleted environment at concentrations of MIC/2, MIC and MIC × 2. Extracts analyzed by high performance liquid chromatography demonstrated flavonoids and phenolic acids. The extracts showed fungistatic effect and no fungicide with MIC >8192 μg/mL, MFC above 8192 μg/mL. The IC50 was calculated ranging from 1803.02 to 5623.41 μg/mL. It has been found that the extracts affect the morphological transition capability, preventing the formation of pseudohyphae and hyphae. Teas and tinctures, therefore, have the potential antifungal, by direct contact, causing inhibition of fungal multiplication and its virulence factor, the cell dimorphism, preventing tissue invasion. Further studies are needed to elucidate the biochemical pathways and genes assets involved in these processes.

  10. Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

    DEFF Research Database (Denmark)

    Jelsbak, Lotte; Thomsen, Line Elnif; Wallrodt, Inke

    2012-01-01

    for studying typhoid fever. Central to its virulence are two major virulence loci Salmonella Pathogenicity Island 1 and 2 (SPI1 and SPI2). SPI1 promotes invasion of epithelial cells, whereas SPI2 enables S. Typhimurium to survive and proliferate within specialized compartments inside host cells. In this study......, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion...

  11. Fiber, food, fuel, and fungal symbionts.

    Science.gov (United States)

    Ruehle, J L; Marx, D H

    1979-10-26

    Virtually all plants of economic importance form mycorrhizae. These absorbing organs of higher plants result from a symbiotic union of beneficial soil fungi and feeder roots. In forestry, the manipulation of fungal symbionts ecologically adapted to the planting site can increase survival and growth of forest trees, particularly on adverse sites. Vesicular-arbuscular mycorrhizae, which occur not only on many trees but also on most cultivated crops, are undoubtedly more important to world food crops. Imperatives for mycorrhizal research in forestry and agriculture are (i) the development of mass inoculum of mycorrhizal fungi, (ii) the interdisciplinary coordination with soil management, plant breeding, cultivation practices, and pest control to ensure maximum survival and development of fungal symbionts in the soil, and (iii) the institution of nursery and field tests to determine the circumstances in which mycorrhizae benefit plant growth in forestry and agri-ecosystems.

  12. Fungal enzymes in the attine ant symbiosis

    DEFF Research Database (Denmark)

    de Fine Licht, Henrik Hjarvard; Schiøtt, Morten; Boomsma, Jacobus Jan

    the more basal attine genera use substrates such as flowers, plant debris, small twigs, insect feces and insect carcasses. This diverse array of fungal substrates across the attine lineage implies that the symbiotic fungus needs different enzymes to break down the plant material that the ants provide...... or different efficiencies of enzyme function. Fungal enzymes that degrade plant cell walls may have functionally co-evolved with the ants in this scenario. We explore this hypothesis with direct measurements of enzyme activity in fungus gardens in 12 species across 8 genera spanning the entire phylogeny...... and diversity of life-styles within the attine clade. We find significant differences in enzyme activity between different genera and life-styles of the ants. How these findings relate to attine ant coevolution and crop optimization are discussed....

  13. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

    Science.gov (United States)

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

    2013-01-01

    virulence of this common zygomycete fungal pathogen.

  14. Burden of serious fungal infections in Bangladesh.

    Science.gov (United States)

    Gugnani, H C; Denning, D W; Rahim, R; Sadat, A; Belal, M; Mahbub, M S

    2017-06-01

    In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.

  15. Burden of serious fungal infections in Ukraine.

    Science.gov (United States)

    Osmanov, Ali; Denning, David W

    2015-10-01

    Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually. © 2015 Blackwell Verlag GmbH.

  16. Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

    Science.gov (United States)

    Barbero, Margherita; Artuso, Emma; Prandi, Cristina

    2018-01-01

    Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Bacterial, Fungal, Parasitic, and Viral Myositis

    OpenAIRE

    Crum-Cianflone, Nancy F.

    2008-01-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyo...

  18. Fungal Systematics and Evolution: FUSE 1

    OpenAIRE

    Crous, Pedro W; Schumacher, René K; Wingfield, Michael J; Lombard, Lorenzo; Giraldo, Alejandra; Christensen, Martha; Gardiennet, Alain; Nakashima, Chiharu; Pereira, Olinto L; Smith, Alexander J; Groenewald, Johannes Z

    2015-01-01

    Fungal Systematics and Evolution (FUSE) is introduced as a new series to expedite the publication of issues relating to the epitypification of formerly described species, report new sexual-asexual connections, the merging of sexual and asexual gen¬era following the end of dual nomenclature, and to describe species or note interesting observations regarding fungi. This first paper includes 18 new combinations, 13 new species, three new genera and one new family. All taxa are ascomycetes, excep...

  19. Invasive fungal infections in endogenous Cushing's syndrome

    Science.gov (United States)

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  20. Burden of Serious Fungal Infections in Argentina

    Directory of Open Access Journals (Sweden)

    Fernando O. Riera

    2018-04-01

    Full Text Available The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS are major problems. An estimated 432 cases of cryptococcal meningitis (CM—90% of them in AIDS patients—and 1177 cases of Pneumocystis pneumonia (PCP occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01% in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality.

  1. HapX-Mediated Iron Homeostasis Is Essential for Rhizosphere Competence and Virulence of the Soilborne Pathogen Fusarium oxysporum[C][W][OA

    Science.gov (United States)

    López-Berges, Manuel S.; Capilla, Javier; Turrà, David; Schafferer, Lukas; Matthijs, Sandra; Jöchl, Christoph; Cornelis, Pierre; Guarro, Josep; Haas, Hubertus; Di Pietro, Antonio

    2012-01-01

    Soilborne fungal pathogens cause devastating yield losses and are highly persistent and difficult to control. During the infection process, these organisms must cope with limited availability of iron. Here we show that the bZIP protein HapX functions as a key regulator of iron homeostasis and virulence in the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect iron uptake but causes derepression of genes involved in iron-consuming pathways, leading to impaired growth under iron-depleted conditions. F. oxysporum strains lacking HapX are reduced in their capacity to invade and kill tomato (Solanum lycopersicum) plants and immunodepressed mice. The virulence defect of ΔhapX on tomato plants is exacerbated by coinoculation of roots with a biocontrol strain of Pseudomonas putida, but not with a siderophore-deficient mutant, indicating that HapX contributes to iron competition of F. oxysporum in the tomato rhizosphere. These results establish a conserved role for HapX-mediated iron homeostasis in fungal infection of plants and mammals. PMID:22968717

  2. CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

    Science.gov (United States)

    Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-01-01

    CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

  3. MaHog1, a Hog1-type mitogen-activated protein kinase gene, contributes to stress tolerance and virulence of the entomopathogenic fungus Metarhizium acridum.

    Science.gov (United States)

    Jin, Kai; Ming, Yue; Xia, Yu Xian

    2012-12-01

    Fungal biocontrol agents have great potential in integrated pest management. However, poor efficacy and sensitivity to various adverse factors have hampered their wide application. In eukaryotic cells, Hog1 kinase plays a critical role in stress responses. In this study, MaHog1 (GenBank accession no. EFY85878), encoding a member of the Hog1/Sty1/p38 mitogen-activated protein kinase family in Metarhizium (Me.) acridum, was identified. Targeted gene disruption was used to analyse the role of MaHog1 in virulence and tolerance of adverse factors. Mutants with MaHog1 depletion showed increased sensitivity to high osmotic stress, high temperature and oxidative stress, and exhibited remarkable resistance to cell wall-disturbing agents. These results suggest that Hog1 kinase has a conserved function in regulating multistress responses among fungi, and that MaHog1 might influence cell wall biogenesis in Me. acridum. Bioassays conducted with topical inoculation and intrahaemocoel injection revealed that MaHog1 is required for both penetration and postpenetration development of Me. acridum. MaHog1 disruption resulted in a significant reduction in virulence, likely due to the combination of a decrease in conidial germination, a reduction in appressorium formation and a decline in growth rate in insect haemolymph, which might be caused by impairing fungal tolerance of various stresses during infection.

  4. A Study Of Fungal Colonization In Newborn

    Directory of Open Access Journals (Sweden)

    S Rashid Husain

    1997-04-01

    Full Text Available Research Problem: What are the factors responsible for fungal colonization in newborns? Objective: To study the pattern of and predisposing fac­tors for the development of superficial candidiasis and fungal colonization in the newborns. Study Design: Prospective study. Setting: Neonatology unitof the Paediatrics department of a teaching hospital. Participants: Randomly selected pregnant mothers admit­ted to the maternity ward and the newborns delivered to them. Sample Size: 120 pregnant mothers and the newborns delivered. Study Variables: Candida, Site of colonization. Statistical Analysis: By tests of significance Results: Candida was isolated from 23 (19.16% infants on the first day increasing to 52 (43.33% infants on the sixth day. The most common site of colonization was oral cavity. Candida colonization was more common in prema­ture infants (p<0.05. Oral thrush was seen in 29 (24.17% infants during the study and a significant number of these infants showed colonization from the first day of life. Conclusions: Fungal colonization of the newborns due to Candida species is quite common, and in the first week of life predominantly occurred in the ora I cavity. Superficial clinical candidiasis, especially oral thrush is more common in those colonized on the first day of life.

  5. Fungal myositis in children: serial ultrasonographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jung Hwa; Lee, Hee Jung; Choi, Jin Soo [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2003-08-01

    To evaluate serial ultrasonographic findings of fungal myositis in children. Eleven lesions caused by fungal myositis and occurring in six children were included in this study. Eight lesions in five children were histopathologically proven and the other three were clinically diagnosed. Serial ultrasonographic findings were retrospectively evaluated in terms of size, location, margin, internal echotexture and adjacent cortical change occurring during the follow-up period ranging from five days to two months. Three patients (50%) had multiple lesions. The sites of involvment were the thigh (n=4), calf (n=3), chest wall (n=2), abdominal wall (n=1) and forearm (n=1). Initially, diffuse muscular swelling was revealed, with ill-defined hypoechoic lesions confined to the muscle layer (n=8). Follow-up examination of eight lesions over a period of 5-10 days showed that round central echogenic lesions were surrounded by previous slightly echogenic lesions (n=6, 75%). Long-term follow-up of five lesions over a two-month period revealed periosteal thickening in one case (20%), and the peristence of echogenic solid nodules in four (80%). Pathologic examination showed that the central lesions correlated with a fungus ball and the peripheral slightly echogenic lesions corresponded to hematoma and necrosis. Serial ultrasonographic findings of fungal myositis in children revealed relatively constant features in each case. In particular, the findings of muscular necrosis and a fungus ball over a period of 5-14 days were thought to be characteristic.

  6. Fungal myositis in children: serial ultrasonographic findings

    International Nuclear Information System (INIS)

    Kwon, Jung Hwa; Lee, Hee Jung; Choi, Jin Soo

    2003-01-01

    To evaluate serial ultrasonographic findings of fungal myositis in children. Eleven lesions caused by fungal myositis and occurring in six children were included in this study. Eight lesions in five children were histopathologically proven and the other three were clinically diagnosed. Serial ultrasonographic findings were retrospectively evaluated in terms of size, location, margin, internal echotexture and adjacent cortical change occurring during the follow-up period ranging from five days to two months. Three patients (50%) had multiple lesions. The sites of involvment were the thigh (n=4), calf (n=3), chest wall (n=2), abdominal wall (n=1) and forearm (n=1). Initially, diffuse muscular swelling was revealed, with ill-defined hypoechoic lesions confined to the muscle layer (n=8). Follow-up examination of eight lesions over a period of 5-10 days showed that round central echogenic lesions were surrounded by previous slightly echogenic lesions (n=6, 75%). Long-term follow-up of five lesions over a two-month period revealed periosteal thickening in one case (20%), and the peristence of echogenic solid nodules in four (80%). Pathologic examination showed that the central lesions correlated with a fungus ball and the peripheral slightly echogenic lesions corresponded to hematoma and necrosis. Serial ultrasonographic findings of fungal myositis in children revealed relatively constant features in each case. In particular, the findings of muscular necrosis and a fungus ball over a period of 5-14 days were thought to be characteristic

  7. Bacterial - Fungal Interactions: ecology, mechanisms and challenges.

    Science.gov (United States)

    Deveau, A; Bonito, G; Uehling, J; Paoletti, M; Becker, M; Bindschedler, S; Hacquard, S; Hervé, V; Labbé, J; Lastovetsky, O A; Mieszkin, S; Millet, L J; Vajna, B; Junier, P; Bonfante, P; Krom, B P; Olsson, S; Elsas, J D van; Wick, L Y

    2018-02-19

    Fungi and bacteria are found living together in a wide variety of environments. Their interactions are significant drivers of many ecosystem functions and are important for the health of plants and animals. A large number of fungal and bacterial families are engaged in complex interactions that lead to critical behavioural shifts of the microorganisms ranging from mutualism to pathogenicity. The importance of bacterial-fungal interactions (BFI) in environmental science, medicine and biotechnology has led to the emergence of a dynamic and multidisciplinary research field that combines highly diverse approaches including molecular biology, genomics, geochemistry, chemical and microbial ecology, biophysics and ecological modelling. In this review, we discuss most recent advances that underscore the roles of BFI across relevant habitats and ecosystems. A particular focus is placed on the understanding of BFI within complex microbial communities and in regards of the metaorganism concept. We also discuss recent discoveries that clarify the (molecular) mechanisms involved in bacterial-fungal relationships, and the contribution of new technologies to decipher generic principles of BFI in terms of physical associations and molecular dialogues. Finally, we discuss future directions for researches in order to catalyse a synergy within the BFI research area and to resolve outstanding questions.

  8. Risk of Fungal Infection to Dental Patients

    Directory of Open Access Journals (Sweden)

    Jaqueline Lopes Damasceno

    2017-01-01

    Full Text Available Fungi can cause various diseases, and some pathogenic fungi have been detected in the water of dental equipment. This environment offers suitable conditions for fungal biofilms to emerge, which can facilitate mycological contamination. This study verified whether the water employed in the dental units of two dental clinics at the University of Franca was contaminated with fungi. This study also evaluated the ability of the detected fungi to form biofilms. The high-revving engine contained the largest average amount of fungi, 14.93 ± 18.18 CFU/mL. The main fungal species verified in this equipment belonged to the genera Aspergillus spp., Fusarium spp., Candida spp., and Rhodotorula spp. Among the isolated filamentous fungi, only one fungus of the genus Fusarium spp. did not form biofilms. As for yeasts, all the Candida spp. isolates grew as biofilm, but none of the Rhodotorula spp. isolates demonstrated this ability. Given that professionals and patients are often exposed to water and aerosols generated by the dental procedure, the several fungal species detected herein represent a potential risk especially to immunocompromised patients undergoing dental treatment. Therefore, frequent microbiological monitoring of the water employed in dental equipment is crucial to reduce the presence of contaminants.

  9. Fungal Production and Manipulation of Plant Hormones.

    Science.gov (United States)

    Fonseca, Sandra; Radhakrishnan, Dhanya; Prasad, Kalika; Chini, Andrea

    2018-01-01

    Living organisms are part of a highly interconnected web of interactions, characterised by species nurturing, competing, parasitizing and preying on one another. Plants have evolved cooperative as well as defensive strategies to interact with neighbour organisms. Among these, the plant-fungus associations are very diverse, ranging from pathogenic to mutualistic. Our current knowledge of plant-fungus interactions suggests a sophisticated coevolution to ensure dynamic plant responses to evolving fungal mutualistic/pathogenic strategies. The plant-fungus communication relies on a rich chemical language. To manipulate the plant defence mechanisms, fungi produce and secrete several classes of biomolecules, whose modeof- action is largely unknown. Upon perception of the fungi, plants produce phytohormones and a battery of secondary metabolites that serve as defence mechanism against invaders or to promote mutualistic associations. These mutualistic chemical signals can be co-opted by pathogenic fungi for their own benefit. Among the plant molecules regulating plant-fungus interaction, phytohormones play a critical role since they modulate various aspects of plant development, defences and stress responses. Intriguingly, fungi can also produce phytohormones, although the actual role of fungalproduced phytohormones in plant-fungus interactions is poorly understood. Here, we discuss the recent advances in fungal production of phytohormone, their putative role as endogenous fungal signals and how fungi manipulate plant hormone balance to their benefits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Effect of hydrophilicity of carbon nanotube arrays on the release rate and activity of recombinant human bone morphogenetic protein-2

    Energy Technology Data Exchange (ETDEWEB)

    Han Zhaojun; Ostrikov, Kostya [Plasma Nanoscience Centre Australia (PNCA), CSIRO Materials Science and Engineering, Lindfield, New South Wales 2070 (Australia); Tan, Cher Ming; Tay, Beng Kang [School of Electrical and Electronic Engineering, Nanyang Technological University, 639798 (Singapore); Peel, Sean A F, E-mail: zhaojun.han@csiro.au [Department of Dentistry, University of Toronto, Toronto, ON, M5G 1G6 (Canada)

    2011-07-22

    Novel nanostructures such as vertically aligned carbon nanotube (CNT) arrays have received increasing interest as drug delivery carriers. In the present study, two CNT arrays with extreme surface wettabilities are fabricated and their effects on the release of recombinant human bone morphogenetic protein-2 (rhBMP-2) are investigated. It is found that the superhydrophilic arrays retained a larger amount of rhBMP-2 than the superhydrophobic ones. Further use of a poloxamer diffusion layer delayed the initial burst and resulted in a greater total amount of rhBMP-2 released from both surfaces. In addition, rhBMP-2 bound to the superhydrophilic CNT arrays remained bioactive while they denatured on the superhydrophobic surfaces. These results are related to the combined effects of rhBMP-2 molecules interacting with poloxamer and the surface, which could be essential in the development of advanced carriers with tailored surface functionalities.

  11. Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

    Directory of Open Access Journals (Sweden)

    Takenobu Katagiri, PhD

    2015-05-01

    Full Text Available Bone morphogenetic protein (BMP was originally discovered by Marshall Urist a half century ago following the observation of a unique activity that induced heterotopic bone formation in skeletal muscle tissue. The molecular mechanisms underlying the induction of heterotopic bone formation in skeletal muscle by BMPs were elucidated through the purification and molecular cloning of BMPs and identification of their functional receptors and downstream effectors, as well as from genetic disorders related to BMP activity. BMPs are important regulators of not only skeletal development and regeneration but also the homeostasis of normal skeletal muscle mass. There is still much to learn about the physiology and pathology at the interface of BMPs and skeletal muscle.

  12. Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall*

    Science.gov (United States)

    Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E.

    2015-01-01

    Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment “ghosts” and applied 2D 13C-13C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. PMID:25825492

  13. Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall.

    Science.gov (United States)

    Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E

    2015-05-29

    Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment "ghosts" and applied 2D (13)C-(13)C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase for anti-fungal therapy

    Directory of Open Access Journals (Sweden)

    Summer R. Hayek

    2014-01-01

    Full Text Available Vacuolar proton-translocating ATPase (V-ATPase is a membrane-bound, multi-subunit enzyme that uses the energy of ATP hydrolysis to pump protons across membranes. V-ATPase activity is critical for pH homeostasis and organelle acidification as well as for generation of the membrane potential that drives secondary transporters and cellular metabolism. V-ATPase is highly conserved across species and is best characterized in the model fungus Saccharomyces cerevisiae (S. cerevisiae. However, recent studies in mammals have identified significant alterations from fungi, particularly in the isoform composition of the 14 subunits and in the regulation of complex disassembly. These differences could be exploited for selectivity between fungi and humans and highlight the potential for V-ATPase as an anti-fungal drug target. Candida albicans (C. albicans is a major human fungal pathogen and causes fatality in 35% of systemic infections, even with anti-fungal treatment. The pathogenicity of C. albicans correlates with environmental, vacuolar, and cytoplasmic pH regulation, and V-ATPase appears to play a fundamental role in each of these processes. Genetic loss of V-ATPase in pathogenic fungi leads to defective virulence, and a comprehensive picture of the mechanisms involved is emerging. Recent studies have explored the practical utility of V-ATPase as an anti-fungal drug target in C. albicans, including pharmacological inhibition, azole therapy, and targeting of downstream pathways. This overview will discuss these studies as well as hypothetical ways to target V-ATPase and novel high-throughput methods for use in future drug discovery screens.

  15. The major Alternaria alternata allergen, Alt a 1: A reliable and specific marker of fungal contamination in citrus fruits.

    Science.gov (United States)

    Gabriel, M F; Uriel, N; Teifoori, F; Postigo, I; Suñén, E; Martínez, J

    2017-09-18

    The ubiquitously present spores of Alternaria alternata can spoil a wide variety of foodstuffs, including a variety of fruits belonging to the Citrus genus. The major allergenic protein of A. alternata, Alt a 1, is a species-specific molecular marker that has been strongly associated with allergenicity and phytopathogenicity of this fungal species. This study aimed to evaluate the potential of the detection of Alt a 1 as a reliable indicator of A. alternata contamination in citrus fruits. To accomplish this aim, sixty oranges were artificially infected with a spore suspension of A. alternata. Internal fruit material was collected at different incubation times (one, two and three weeks after the fungal inoculation) and used for both total RNA extraction and protein extraction. Alt a 1 detection was then performed by polymerase chain reaction (PCR) amplification using Alt a 1 specific primers and by enzyme-linked immunosorbent assay (ELISA). The experimental model presented in this work was effective to simulate the typical Alternaria black rot phenotype and its progression. Although both PCR and ELISA techniques have been successfully carried out for detecting Alt a 1 allergen in A. alternata infected oranges, the PCR method was found to be more sensitive than ELISA. Nevertheless, ELISA results were highly valuable to demonstrate that considerable amounts of Alt a 1 are produced during A. alternata fruit infection process, corroborating the recently proposed hypothesis that this protein plays a role in the pathogenicity and virulence of Alternaria species. Such evidence suggests that the detection of Alt a 1 by PCR-based assay may be used as a specific indicator of the presence of pathogenic and allergenic fungal species, A. alternata, in fruits. This knowledge can be employed to control the fungal infection and mitigate agricultural losses as well as human exposure to A. alternata allergens and toxins. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Xiao Wei

    2018-01-01

    Full Text Available Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA, and matrix Gla protein (MGP in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r=0.929; P<0.01 and serum BMP-4 (r=0.702; P<0.01 levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

  17. Expression of cytokines in aqueous humor from fungal keratitis patients.

    Science.gov (United States)

    Zhang, Yingnan; Liang, Qingfeng; Liu, Yang; Pan, Zhiqiang; Baudouin, Christophe; Labbé, Antoine; Lu, Qingxian

    2018-04-19

    Although a series of reports on corneal fungal infection have been published, studies on pathogenic mechanisms and inflammation-associated cytokines remain limited. In this study, aqueous humor samples from fungal keratitis patients were collected to examine cytokine patterns and cellular profile for the pathogenesis of fungal keratitis. The aqueous humor samples were collected from ten patients with advanced stage fungal keratitis. Eight aqueous humor samples from patients with keratoconus or corneal dystrophy were taken as control. Approximately 100 μl to 300 μl of aqueous humor in each case were obtained for examination. The aqueous humor samples were centrifuged and the cells were stained and examined under optical microscope. Bacterial and fungal cultures were performed on the aqueous humor and corneal buttons of all patients. Cytokines related to inflammation including IL-1β, IL-6, IL-8, IL-10, TNF-α, and IFN-γ were examined using multiplex bead-based Luminex liquid protein array systems. Fungus infection was confirmed in these ten patients by smear stains and/or fungal cultures. Bacterial and fungal cultures revealed negative results in all aqueous humor specimens. Polymorphonuclear leukocytes were the predominant infiltrating cells in the aqueous humor of fungal keratitis. At the advanced stages of fungal keratitis, the levels of IL-1β, IL-6, IL-8, and IFN-γ in the aqueous humor were significantly increased when compared with control (phumor was associated with fungal keratitis.

  18. Transplant tourism and invasive fungal infection.

    Science.gov (United States)

    Al Salmi, I; Metry, A M; Al Ismaili, F; Hola, A; Al Riyami, M; Khamis, F; Al-Abri, S

    2018-04-01

    Deceased and live-related renal transplants (RTXs) are approved procedures that are performed widely throughout the world. In certain regions, commercial RTX has become popular, driven by financial greed. This retrospective, descriptive study was performed at the Royal Hospital from 2013 to 2015. Data were collected from the national kidney transplant registry of Oman. All transplant cases retrieved were divided into two groups: live-related RTX performed in Oman and commercial-unrelated RTX performed abroad. These groups were then divided again into those with and without evidence of fungal infection, either in the wound or renal graft. A total of 198 RTX patients were identified, of whom 162 (81.8%) had undergone a commercial RTX that was done abroad. Invasive fungal infections (IFIs) were diagnosed in 8% of patients who had undergone a commercial RTX; of these patients, 76.9% underwent a nephrectomy and 23.1% continued with a functioning graft. None of the patients with RTXs performed at the Royal Hospital contracted an IFI. The most common fungal isolates were Aspergillus species (including Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, and Aspergillus nigricans), followed by Zygomycetes. However, there was no evidence of fungal infection including Aspergillus outside the graft site. Computed tomography (CT) findings showed infarction of the graft, renal artery thrombosis, aneurysmal dilatation of the external iliac artery, fungal ball, or just the presence of a perigraft collection. Of the total patients with IFIs, 23.1% died due to septic shock and 53.8% were alive and on hemodialysis. The remaining 23.1% who did not undergo nephrectomy demonstrated acceptable graft function. This is the largest single-center study on commercial RTX reporting the highest number of patients with IFI acquired over a relatively short period of time. Aspergillus spp were the main culprit fungi, with no Candida spp being isolated. A high index of suspicion might

  19. Fungal Urinary Tract Infection in Burn Patients‎

    Directory of Open Access Journals (Sweden)

    Suad Yousuf Aldorkee

    2017-11-01

    Full Text Available Background: Urinary tract infection is the most common hospital-acquired infection. Fungal species are unusual causes of urinary tract infection in healthy individuals, but common in the hospital setting or among patients with predisposing diseases and structural abnormalities of the kidney and collecting system. Burn patients are susceptible to nosocomial infections owing to the immunocompromising effects of burn injury, cutaneous and respiratory tract injury, prolonged intensive care unit stays and broad-spectrum antibiotic therapy. Objective: The study population includes adult patients of both genders who presented with different percentages of body burns. Urine sample was collected from each patient at the time of admission and weekly thereafter for 6 weeks and sent for general urine examination and urine culture to test for the possibility of fungal growth. Those who found to develop fungal UTI by urine culture during their hospitalization and had no infection at the time of admission were selected as subjects for our study. Results: 28 (18.6% patients had positive fungal culture during their hospitalization, 11 of them were males and 17 were females, the most common age of presentation was 41-50 years and the mean age ± SD was (44.4 ± 10.7 years. The most common isolated fungi were Candida albicans (64.3%, followed by Candida glabrata (21.4% and Candida tropicalis (7.1%. The majority of patients developed infection within the 2nd and 3rd weeks of hospitalization, however, those who presented with total body surface area burned > 40% developed an earlier infection within the 1st week. Female gender, urethral catheterization and diabetes mellitus were significantly associated with higher risk of infection as the P values were 0.03, 0.005 and 0.004 respectively. Conclusion: Fungal urinary tract infection occurred in 18.6% of burn patients. The most common causative fungi are candida species. Advanced age, female gender, high percentage of

  20. Experimental Infection of Snakes with Ophidiomyces ophiodiicola Causes Pathological Changes That Typify Snake Fungal Disease.

    Science.gov (United States)

    Lorch, Jeffrey M; Lankton, Julia; Werner, Katrien; Falendysz, Elizabeth A; McCurley, Kevin; Blehert, David S

    2015-11-17

    infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative fungal virulence, host response, and host-pathogen evolution. Copyright © 2015 Lorch et al.

  1. Caenorhabditis elegans reveals novel Pseudomonas aeruginosa virulence mechanism

    NARCIS (Netherlands)

    Utari, Putri Dwi; Quax, Wim J.

    The susceptibility of Caenorhabditis elegans to different virulent phenotypes of Pseudomonas aeruginosa makes the worms an excellent model for studying host-pathogen interactions. Including the recently described liquid killing, five different killing assays are now available offering superb

  2. Helicobacter pylori virulence factors in development of gastric carcinoma.

    Science.gov (United States)

    Wang, Ming-Yi; Liu, Xiao-Fei; Gao, Xiao-Zhong

    2015-01-01

    Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.

  3. Molecular Detection of Virulence Genes and Antibiotic Resistance ...

    African Journals Online (AJOL)

    Pathogen, E. coli O157:H7, virulence genes, antibiotic-resistance, beef meat. Correspondence: ... box to the laboratory for further processing. Isolation and identification of ... Technologies (IDT) Inc, U.S.A. The sequences and annealing ...

  4. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides

    NARCIS (Netherlands)

    Li, C.H.; Cervantes, M.; Springer, D.J.; Boekhout, T.; Ruiz-Vazquez, R.M.; Torres-Martinez, S.R.; Heitman, J.; Lee, S.S.

    2011-01-01

    Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a

  5. Virulence Factors Associated with Enterococcus Faecalis Infective Endocarditis

    DEFF Research Database (Denmark)

    Madsen, Kristian T; Skov, Marianne N; Gill, Sabine

    2017-01-01

    INTRODUCTION: The enterococci are accountable for up to 20% of all cases of infective endocarditis, with Enterococcus faecalis being the primary causative isolate. Infective endocarditis is a life-threatening infection of the endocardium that results in the formation of vegetations. Based...... on a literature review, this paper provides an overview of the virulence factors associated with E. faecalis infective endocarditis. Furthermore, it reports the effects of active or passive immunization against some of these involved factors. INDIVIDUAL VIRULENCE FACTORS: Nine virulence factors have in particular...... been associated with E. faecalis infective endocarditis. Absence of these factors entailed attenuation of strains in both mixed- and mono-bacterial infection endocarditis models as well as in in vitro and ex vivo assays when compared to their virulence factor expressing parental strains. PATHOGENESIS...

  6. Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

    Science.gov (United States)

    Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

    2015-01-01

    Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

  7. Influence of Multiple Infection and Relatedness on Virulence: Disease Dynamics in an Experimental Plant Population and Its Castrating Parasite

    Science.gov (United States)

    Buono, Lorenza; López-Villavicencio, Manuela; Shykoff, Jacqui A.; Snirc, Alodie; Giraud, Tatiana

    2014-01-01

    The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration. PMID:24892951

  8. Invasion thresholds and the evolution of nonequilibrium virulence

    OpenAIRE

    Bull, J. J.; Ebert, D.

    2008-01-01

    Abstract The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonopti...

  9. Investigating the ?Trojan Horse? Mechanism of Yersinia pestis Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McCutchen-Maloney, S L; Fitch, J P

    2005-02-08

    Yersinia pestis, the etiological agent of plague, is a Gram-negative, highly communicable, enteric bacterium that has been responsible for three historic plague pandemics. Currently, several thousand cases of plague are reported worldwide annually, and Y. pestis remains a considerable threat from a biodefense perspective. Y. pestis infection can manifest in three forms: bubonic, septicemic, and pneumonic plague. Of these three forms, pneumonic plague has the highest fatality rate ({approx}100% if left untreated), the shortest intervention time ({approx}24 hours), and is highly contagious. Currently, there are no rapid, widely available vaccines for plague and though plague may be treated with antibiotics, the emergence of both naturally occurring and potentially engineered antibiotic resistant strains makes the search for more effective therapies and vaccines for plague of pressing concern. The virulence mechanism of this deadly bacterium involves induction of a Type III secretion system, a syringe-like apparatus that facilitates the injection of virulence factors, termed Yersinia outer membrane proteins (Yops), into the host cell. These virulence factors inhibit phagocytosis and cytokine secretion, and trigger apoptosis of the host cell. Y. pestis virulence factors and the Type III secretion system are induced thermally, when the bacterium enters the mammalian host from the flea vector, and through host cell contact (or conditions of low Ca{sup 2+} in vitro). Apart from the temperature increase from 26 C to 37 C and host cell contact (or low Ca{sup 2+} conditions), other molecular mechanisms that influence virulence induction in Y. pestis are largely uncharacterized. This project focused on characterizing two novel mechanisms that regulate virulence factor induction in Y. pestis, immunoglobulin G (IgG) binding and quorum sensing, using a real-time reporter system to monitor induction of virulence. Incorporating a better understanding of the mechanisms of virulence

  10. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    Directory of Open Access Journals (Sweden)

    Ann Ray

    2016-07-01

    Full Text Available Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells.

  11. Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients.

    Science.gov (United States)

    Amissah, Nana Ama; Chlebowicz, Monika A; Ablordey, Anthony; Tetteh, Caitlin S; Prah, Isaac; van der Werf, Tjip S; Friedrich, Alex W; van Dijl, Jan Maarten; Stienstra, Ymkje; Rossen, John W

    2017-06-01

    Buruli ulcer (BU) is a necrotizing infection of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU wounds may also be colonized with other microorganisms including Staphylococcus aureus. This study aimed to characterize the virulence factors of S. aureus isolated from BU patients. Previously sequenced genomes of 21 S. aureus isolates from BU patients were screened for the presence of virulence genes. The results show that all S. aureus isolates harbored on their core genomes genes for known virulence factors like α-hemolysin, and the α- and β-phenol soluble modulins. Besides the core genome virulence genes, mobile genetic elements (MGEs), i.e. prophages, genomic islands, pathogenicity islands and a Staphylococcal cassette chromosome (SCC) were found to carry different combinations of virulence factors, among them genes that are known to encode factors that promote immune evasion, superantigens and Panton-Valentine Leucocidin. The present observations imply that the S. aureus isolates from BU patients harbor a diverse repertoire of virulence genes that may enhance bacterial survival and persistence in the wound environment and potentially contribute to delayed wound healing. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  12. A Pectate Lyase-Coding Gene Abundantly Expressed during Early Stages of Infection Is Required for Full Virulence in Alternaria brassicicola.

    Directory of Open Access Journals (Sweden)

    Yangrae Cho

    Full Text Available Alternaria brassicicola causes black spot disease of Brassica species. The functional importance of pectin digestion enzymes and unidentified phytotoxins in fungal pathogenesis has been suspected but not verified in A. brassicicola. The fungal transcription factor AbPf2 is essential for pathogenicity and induces 106 genes during early pathogenesis, including the pectate lyase-coding gene, PL1332. The aim of this study was to test the importance and roles of PL1332 in pathogenesis. We generated deletion strains of the PL1332 gene, produced heterologous PL1332 proteins, and evaluated their association with virulence. Deletion strains of the PL1332 gene were approximately 30% less virulent than wild-type A. brassicicola, without showing differences in colony expansion on solid media and mycelial growth in nutrient-rich liquid media or minimal media with pectins as a major carbon source. Heterologous PL1332 expressed as fusion proteins digested polygalacturons in vitro. When the fusion proteins were injected into the apoplast between leaf veins of host plants the tissues turned dark brown and soft, resembling necrotic leaf tissue. The PL1332 gene was the first example identified as a general toxin-coding gene and virulence factor among the 106 genes regulated by the transcription factor, AbPf2. It was also the first gene to have its functions investigated among the 19 pectate lyase genes and several hundred putative cell-wall degrading enzymes in A. brassicicola. These results further support the importance of the AbPf2 gene as a key pathogenesis regulator and possible target for agrochemical development.

  13. Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

    Science.gov (United States)

    Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

    2012-01-01

    Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

  14. Group X hybrid histidine kinase Chk1 is dispensable for stress adaptation, host-pathogen interactions and virulence in the opportunistic yeast Candida guilliermondii.

    Science.gov (United States)

    Navarro-Arias, María J; Dementhon, Karine; Defosse, Tatiana A; Foureau, Emilien; Courdavault, Vincent; Clastre, Marc; Le Gal, Solène; Nevez, Gilles; Le Govic, Yohann; Bouchara, Jean-Philippe; Giglioli-Guivarc'h, Nathalie; Noël, Thierry; Mora-Montes, Hector M; Papon, Nicolas

    2017-09-01

    Hybrid histidine kinases (HHKs) progressively emerge as prominent sensing proteins in the fungal kingdom and as ideal targets for future therapeutics. The group X HHK is of major interest, since it was demonstrated to play an important role in stress adaptation, host-pathogen interactions and virulence in some yeast and mold models, and particularly Chk1, that corresponds to the sole group X HHK in Candida albicans. In the present work, we investigated the role of Chk1 in the low-virulence species Candida guilliermondii, in order to gain insight into putative conservation of the role of group X HHK in opportunistic yeasts. We demonstrated that disruption of the corresponding gene CHK1 does not influence growth, stress tolerance, drug susceptibility, protein glycosylation or cell wall composition in C. guilliermondii. In addition, we showed that loss of CHK1 does not affect C. guilliermondii ability to interact with macrophages and to stimulate cytokine production by human peripheral blood mononuclear cells. Finally, the C. guilliermondii chk1 null mutant was found to be as virulent as the wild-type strain in the experimental model Galleria mellonella. Taken together, our results demonstrate that group X HHK function is not conserved in Candida species. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. Disruption of the GABA shunt affects mitochondrial respiration and virulence in the cereal pathogen Fusarium graminearum.

    Science.gov (United States)

    Bönnighausen, Jakob; Gebhard, Daniel; Kröger, Cathrin; Hadeler, Birgit; Tumforde, Thomas; Lieberei, Reinhard; Bergemann, Jörg; Schäfer, Wilhelm; Bormann, Jörg

    2015-12-01

    The cereal pathogen Fusarium graminearum threatens food and feed production worldwide. It reduces the yield and poisons the remaining kernels with mycotoxins, notably deoxynivalenol (DON). We analyzed the importance of gamma-aminobutanoic acid (GABA) metabolism for the life cycle of this fungal pathogen. GABA metabolism in F. graminearum is partially regulated by the global nitrogen regulator AreA. Genetic disruption of the GABA shunt by deletion of two GABA transaminases renders the pathogen unable to utilize the plant stress metabolites GABA and putrescine. The mutants showed increased sensitivity against oxidative stress, GABA accumulation in the mycelium, downregulation of two key enzymes of the TCA cycle, disturbed potential gradient in the mitochondrial membrane and lower mitochondrial oxygen consumption. In contrast, addition of GABA to the wild type resulted in its rapid turnover and increased mitochondrial steady state oxygen consumption. GABA concentrations are highly upregulated in infected wheat tissues. We conclude that GABA is metabolized by the pathogen during infection increasing its energy production, whereas the mutants accumulate GABA intracellularly resulting in decreased energy production. Consequently, the GABA mutants are strongly reduced in virulence but, because of their DON production, are able to cross the rachis node. © 2015 John Wiley & Sons Ltd.

  16. The effect of Zuccagnia punctata, an Argentine medicinal plant, on virulence factors from candida species.

    Science.gov (United States)

    Gabriela, Nuño; Rosa, Alberto María; Catiana, Zampini Iris; Soledad, Cuello; Mabel, Ordoñez Roxana; Esteban, Sayago Jorge; Veronica, Baroni; Daniel, Wunderlin; Ines, Isla María

    2014-07-01

    Zuccagnia punctata Cav. has been used as a traditional medicine in Argentina for the treatment of bacterial and fungal infections. In this study, we evaluated the ability of Z. punctata extract (ZpE) and compounds isolated from it to inhibit the growth and virulence factors of Candida species. ZpE showed inhibitory activity against planktonic cells of all assayed Candida species with MIC values of 400 microg/mL and with MFC values between 400 and 1,200 microg/mL. The principal identified compounds by HPLC-MS/MS and UV-VIS were chalcones (2',4'-dihydroxy-3'-methoxychalcone, 2',4'- dihydroxychalcone), flavones (galangin, 3,7-dihydroxyflavone and chrysin) and flavanones (naringenin, 7-hydroxyflavanone and pinocembrine). These compounds were more effective as inhibitors than the extracts upon biofilm formation as well as on preformed Candida biofilm and yeast germ tube formation. Furthermore, ZpE and chalcones are able to inhibit exoenzymes, which are responsible for the invasion mechanisms of the pathogens. All these effects could moderate colonization, thereby suppressing the pathogen invasive potential. Our results indicate that ZpE and chalcones could be used in antifungal therapy.

  17. Sensitization to fungal allergens: Resolved and unresolved issues

    Directory of Open Access Journals (Sweden)

    Yuma Fukutomi

    2015-10-01

    Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient.

  18. MoDUO1, a Duo1-like gene, is required for full virulence of the rice blast fungus Magnaporthe oryzae.

    Science.gov (United States)

    Peng, Haowen; Feng, Youjun; Zhu, Xiaohui; Lan, Xiuwan; Tang, Mei; Wang, Jinzi; Dong, Haitao; Chen, Baoshan

    2011-12-01

    Duo1, a major component of the Dam1 complex which has been found in two species of yeast (the budding yeast Saccharomyces cerevisae and the fission yeast Schizosaccharomyces pombe), is involved in mitosis-related chromosome segregation, while its relevance to pathogenicity in filamentous fungi remains unclear. This report elucidated this very fact in the case of the rice blast fungus Magnaporthe oryzae. A gene designated MoDUO1 that encodes a Duo1-like homolog (MoDuo1) was discovered in the M. oryzae genome. Two types of MoDUO1 mutants were obtained using genetic approaches of Agrobacterium-mediated gene disruption and homologous recombination. Both disruption and deletion of MoDUO1 can exert profound effects on the formation pattern of conidiophores and conidial morphology, such as abnormal nucleic numbers in conidia and delayed extension of infectious hyphae. Intriguingly, plant infection assays demonstrated that inactivation of MoDUO1 significantly attenuates the virulence in its natural host rice leaves, and functional complementation can restore it. Subcellular localization assays showed that MoDuo1 is mainly distributed in the cytosol of fungal cells. Proteomics-based investigation revealed that the expression of four mitosis-related proteins is shut down in the MoDUO1 mutant, suggesting that MoDuo1 may have a function in mitosis. In light of the fact that Duo1 orthologs are widespread in plant and human fungal pathogens, our finding may represent a common mechanism underlying fungal virulence. To the best of our knowledge, this is the first example of linking a Duo1-like homolog to the pathogenesis of a pathogenic fungus, which might provide clues to additional studies on the role of Dam1 complex in M. oryzae and its interaction with rice.

  19. The expression and evolution of virulence in multiple infections: the role of specificity, relative virulence and relative dose.

    Science.gov (United States)

    Ben-Ami, Frida; Routtu, Jarkko

    2013-05-03

    Multiple infections of the same host by different strains of the same microparasite species are believed to play a crucial role during the evolution of parasite virulence. We investigated the role of specificity, relative virulence and relative dose in determining the competitive outcome of multiple infections in the Daphnia magna-Pasteuria ramosa host-parasite system. We found that infections by P. ramosa clones (single genotype) were less virulent and produced more spores than infections by P. ramosa isolates (possibly containing multiple genotypes). We also found that two similarly virulent isolates of P. ramosa differed considerably in their within-host competitiveness and their effects on host offspring production when faced with coinfecting P. ramosa isolates and clones. Although the relative virulence of a P. ramosa isolate/clone appears to be a good indicator of its competitiveness during multiple infections, the relative dose may alter the competitive outcome. Moreover, spore counts on day 20 post-infection indicate that the competitive outcome is largely decided early in the parasite's growth phase, possibly mediated by direct interference or apparent competition. Our results emphasize the importance of epidemiology as well as of various parasite traits in determining the outcome of within-host competition. Incorporating realistic epidemiological and ecological conditions when testing theoretical models of multiple infections, as well as using a wider range of host and parasite genotypes, will enable us to better understand the course of virulence evolution.

  20. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

    Science.gov (United States)

    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  1. Natural occurrence of fungi and fungal metabolites in moldy tomatoes

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    Fresh tomatoes, homegrown and from supermarkets, with developing fungal lesions were collected. Each lesion was sampled, and the resulting fungal cultures were identified morphologically, and extracted for analyzes of secondary metabolites. The tomatoes were incubated at 25 degreesC for a week....... extracted, and analyzed for fungal metabolites. Extracts from pure cultures were compared with extracts from the moldy tomatoes and fungal metabolite standards in two HPLC systems with DAD and FLD detection. The results showed that Penicillium tularense, Stemphylium eturmiunum. and S. cf. lycopersici were...

  2. Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism

    Science.gov (United States)

    Khalil, Zeinab G.; Kalansuriya, Pabasara; Capon, Robert J.

    2014-01-01

    We report on a preliminary investigation of the use the Gram-negative bacterial cell wall constituent lipopolysaccharide (LPS) as a natural chemical cue to stimulate and alter the expression of fungal secondary metabolism. Integrated high-throughput micro-cultivation and micro-analysis methods determined that 6 of 40 (15%) of fungi tested responded to an optimal exposure to LPS (0.6 ng/mL) by activating, enhancing or accelerating secondary metabolite production. To explore the possible mechanisms behind this effect, we employed light and fluorescent microscopy in conjunction with a nitric oxide (NO)-sensitive fluorescent dye and an NO scavenger to provide evidence that LPS stimulation of fungal secondary metabolism coincided with LPS activation of NO. Several case studies demonstrated that LPS stimulation can be scaled from single microplate well (1.5 mL) to preparative (>400 mL) scale cultures. For example, LPS treatment of Penicillium sp. (ACM-4616) enhanced pseurotin A and activated pseurotin A1 and pseurotin A2 biosynthesis, whereas LPS treatment of Aspergillus sp. (CMB-M81F) substantially accelerated and enhanced the biosynthesis of shornephine A and a series of biosynthetically related ardeemins and activated production of neoasterriquinone. As an indication of broader potential, we provide evidence that cultures of Penicillium sp. (CMB-TF0411), Aspergillus niger (ACM-4993F), Rhizopus oryzae (ACM-165F) and Thanatephorus cucumeris (ACM-194F) were responsive to LPS stimulation, the latter two examples being particular noteworthy as neither are known to produce secondary metabolites. Our results encourage the view that LPS stimulation can be used as a valuable tool to expand the molecular discovery potential of fungal strains that either have been exhaustively studied by or are unresponsive to traditional culture methodology. PMID:25379339

  3. Fungal cell gigantism during mammalian infection.

    Directory of Open Access Journals (Sweden)

    Oscar Zaragoza

    2010-06-01

    Full Text Available The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  4. Complications of hematopoietic stem transplantation: Fungal infections.

    Science.gov (United States)

    Omrani, Ali S; Almaghrabi, Reem S

    2017-12-01

    Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients. The improved diagnostic performance of serum biomarkers such as galactomannan and β-D-glucan, as well as polymerase chain reaction assays has allowed the development of diagnostic-driven antifungal therapy strategies for high risk patients. Diagnostic-driven approaches have resulted in reduced unnecessary antifungal exposure, improved diagnosis of invasive fungal disease, and reduced costs without increased risk of mortality. The appropriateness of diagnostic-driven antifungal strategy for individual HSCT centers depends on the availability and turnaround times for diagnostics, multidisciplinary expertise, and the local epidemiology of invasive fungal infections. Echinocandins are the treatment of choice for invasive candidiasis in most HSCT recipients. Fluconazole may be used for the treatment of invasive candidiasis in hemodynamically stable patients with no prior azole exposure. The primary treatment of choice for invasive aspergillosis is voriconazole. Alternatives include isavuconazole and lipid formulations of amphotericin. Currently available evidence does not support routine primary combination antifungal therapy for invasive aspergillosis. However, combination salvage antifungal therapy may be considered in selected patients. Therapeutic drug monitoring is recommended for the majority of HSCT recipients on itraconazole, posaconazole, or voriconazole. Copyright © 2017

  5. Optic neuropathy due to allergic fungal rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Jiji Tresa Cyriac

    2011-01-01

    Full Text Available An uncommon case of allergic fungal rhinosinusitis presented to the ophthalmology outpatient department of our hospital with complaints of blurred vision in the right eye of a few days duration and vague complaints of pain around the eyes. The visual acuity on examination was grossly reduced in the right eye and normal in the left eye. Color vision was normal. Anterior segment examination including pupils was normal. Dilated fundus examination was normal except for temporal pallor in the right optic disc. Automated perimetry and magnetic resonance imaging (MRI scan of brain and orbit were done. The imaging report showed a bilateral pansinusitis with pressure on the right optic nerve. Perimetry showed a superior field defect on the right side. ENT consultation and computed tomography (CT with contrast helped to diagnose this as a case of allergic fungal rhinosinusitis. The patient was started on systemic steroids under the care of the ENT surgeon. After a few days, pre-operative assessment showed a gross improvement of visual acuity. Endoscopic sinus surgery was done to remove the polyps and thick mucus material. Histopathologic examination confirmed allergic fungal mucin. Days after surgery, the visual acuity improved further and repeat perimetry showed gross improvement in the visual field. Good history taking and a detailed ophthalmic examination, keeping in mind the probable causes of loss of vision of few days duration with no findings other than a decreased visual acuity and a suspicious disc, were key to the early diagnosis and investigation in this case. This helped in early referral and management of the case before permanent damage and irreversible visual loss occurred. The optic nerve is a cranial nerve which, once damaged permanently, will not regenerate. The amount of sinus involvement was extensive on both sides and invariably the left optic nerve would have been involved in a few days, if intervention was delayed.

  6. Fungal cell gigantism during mammalian infection.

    Science.gov (United States)

    Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

    2010-06-17

    The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  7. Fungal infections of the mucous membrane.

    Science.gov (United States)

    Marques, Silvio Alencar

    2010-01-01

    A clinical review of three potentially severe fungal diseases, which are characterized in many cases by mucosal involvement, is presented. They are paracoccidioidomycosis, histoplasmosis, and mucormycosis. Mucosal involvement for paracoccidioidomycosis and rhinocerebral mucormycosis is frequent. Thus, oral involvement may provide early clue for diagnosis. In paracoccidioidomycosis, the mucosal lesion classically shows superficial ulcers with granular appearance and hemorrhagic points, usually on lips, palate, and jugal mucosa. In mucormycosis, necrosis of the palate followed for purulent discharge is a hallmark of rhinocerebral disease. Treatment with amphotericin B desoxycholate or the new second-generation triazoles is highly efficacious.

  8. Bacterial and fungal markers in tobacco smoke

    International Nuclear Information System (INIS)

    Szponar, B.; Pehrson, C.; Larsson, L.

    2012-01-01

    Previous research has demonstrated that cigarette smoke contains bacterial and fungal components including lipopolysaccharide (LPS) and ergosterol. In the present study we used gas chromatography–mass spectrometry to analyze tobacco as well as mainstream and second hand smoke for 3-hydroxy fatty acids (3-OH FAs) of 10 to 18 carbon chain lengths, used as LPS markers, and ergosterol, used as a marker of fungal biomass. The air concentrations of LPS were 0.0017 nmol/m 3 (N = 5) and 0.0007/m 3 (N = 6) in the smoking vs. non-smoking rooms (p = 0.0559) of the studied private houses, and 0.0231 nmol/m 3 (N = 5) vs. 0.0006 nmol/m 3 (N = 5) (p = 0.0173), respectively, at the worksite. The air concentrations of ergosterol were also significantly higher in rooms with ongoing smoking than in rooms without smoking. A positive correlation was found between LPS and ergosterol in rooms with smoking but not in rooms without smoking. 3-OH C14:0 was the main 3-OH FA, followed by 3-OH C12:0, both in mainstream and second hand smoke and in phenol:water smoke extracts prepared in order to purify the LPS. The Limulus activity of the phenolic phase of tobacco was 3900 endotoxin units (EU)/cigarette; the corresponding amount of the smoke, collected on filters from 8 puffs, was 4 EU/cigarette. Tobacco smoking has been associated with a range of inflammatory airway conditions including COPD, asthma, bronchitis, alveolar hypersensitivity etc. Significant levels of LPS and ergosterol were identified in tobacco smoke and these observations support the hypothesis that microbial components of tobacco smoke contribute to inflammation and airway disease. -- Highlights: ► Air concentration of bacterial and fungal markers is significantly higher in rooms with ongoing smoking than without smoking. ► Bacterial LPS correlates with fungal marker in rooms with ongoing smoking but not without smoking. ► LPS from mainstream smoke contains 3-hydroxy 14:0 and 12:0 fatty acids in similar proportion as

  9. Fungal Fourniers Gangrene in an Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Winston Crowell

    2016-01-01

    Full Text Available Fournier's Gangrene is a rapidly progressive necrotizing fasciitis of the groin, perianal and perineal region that is often polymicrobial in nature, often averaging 3 species of bacteria per patient. The typical infection can be due to a host of microbes, including gram positive, gram negative and anaerobic species including. Many of the causative organisms are found in the normal microbial flora of the perineum. Therefore, Fourniers is an opportunistic infection most commonly affecting the immunosuppressed. The majority of Fournier's gangrene are bacterial; however there have been cases of fungal Fournier's gangrene reported in the literature.

  10. Bacterial and fungal markers in tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Szponar, B., E-mail: szponar@iitd.pan.wroc.pl [Lund University, Dept. of Laboratory Medicine, Soelvegatan 23, 223 62 Lund (Sweden); Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw (Poland); Pehrson, C.; Larsson, L. [Lund University, Dept. of Laboratory Medicine, Soelvegatan 23, 223 62 Lund (Sweden)

    2012-11-01

    Previous research has demonstrated that cigarette smoke contains bacterial and fungal components including lipopolysaccharide (LPS) and ergosterol. In the present study we used gas chromatography-mass spectrometry to analyze tobacco as well as mainstream and second hand smoke for 3-hydroxy fatty acids (3-OH FAs) of 10 to 18 carbon chain lengths, used as LPS markers, and ergosterol, used as a marker of fungal biomass. The air concentrations of LPS were 0.0017 nmol/m{sup 3} (N = 5) and 0.0007/m{sup 3} (N = 6) in the smoking vs. non-smoking rooms (p = 0.0559) of the studied private houses, and 0.0231 nmol/m{sup 3} (N = 5) vs. 0.0006 nmol/m{sup 3} (N = 5) (p = 0.0173), respectively, at the worksite. The air concentrations of ergosterol were also significantly higher in rooms with ongoing smoking than in rooms without smoking. A positive correlation was found between LPS and ergosterol in rooms with smoking but not in rooms without smoking. 3-OH C14:0 was the main 3-OH FA, followed by 3-OH C12:0, both in mainstream and second hand smoke and in phenol:water smoke extracts prepared in order to purify the LPS. The Limulus activity of the phenolic phase of tobacco was 3900 endotoxin units (EU)/cigarette; the corresponding amount of the smoke, collected on filters from 8 puffs, was 4 EU/cigarette. Tobacco smoking has been associated with a range of inflammatory airway conditions including COPD, asthma, bronchitis, alveolar hypersensitivity etc. Significant levels of LPS and ergosterol were identified in tobacco smoke and these observations support the hypothesis that microbial components of tobacco smoke contribute to inflammation and airway disease. -- Highlights: Black-Right-Pointing-Pointer Air concentration of bacterial and fungal markers is significantly higher in rooms with ongoing smoking than without smoking. Black-Right-Pointing-Pointer Bacterial LPS correlates with fungal marker in rooms with ongoing smoking but not without smoking. Black-Right-Pointing-Pointer LPS

  11. Aureusimines in Staphylococcus aureus are not involved in virulence.

    Science.gov (United States)

    Sun, Fei; Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; He, Chuan; Bae, Taeok

    2010-12-29

    Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS), raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process. Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment. Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal virulence.

  12. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides.

    Science.gov (United States)

    Li, Charles H; Cervantes, Maria; Springer, Deborah J; Boekhout, Teun; Ruiz-Vazquez, Rosa M; Torres-Martinez, Santiago R; Heitman, Joseph; Lee, Soo Chan

    2011-06-01

    Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (-) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (-) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have

  13. Aureusimines in Staphylococcus aureus are not involved in virulence.

    Directory of Open Access Journals (Sweden)

    Fei Sun

    2010-12-01

    Full Text Available Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS, raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process.Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment.Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal

  14. A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces.

    Directory of Open Access Journals (Sweden)

    Robert King

    2017-10-01

    Full Text Available Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast "yeast-like" growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2. Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2 suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices.

  15. A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces

    Science.gov (United States)

    Plummer, Amy; Halsey, Kirstie; Lovegrove, Alison; Hammond-Kosack, Kim

    2017-01-01

    Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast “yeast-like” growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices. PMID:29020037

  16. Defining the predicted protein secretome of the fungal wheat leaf pathogen Mycosphaerella graminicola.

    Directory of Open Access Journals (Sweden)

    Alexandre Morais do Amaral

    Full Text Available The Dothideomycete fungus Mycosphaerella graminicola is the causal agent of Septoria tritici blotch, a devastating disease of wheat leaves that causes dramatic decreases in yield. Infection involves an initial extended period of symptomless intercellular colonisation prior to the development of visible necrotic disease lesions. Previous functional genomics and gene expression profiling studies have implicated the production of secreted virulence effector proteins as key facilitators of the initial symptomless growth phase. In order to identify additional candidate virulence effectors, we re-analysed and catalogued the predicted protein secretome of M. graminicola isolate IPO323, which is currently regarded as the reference strain for this species. We combined several bioinformatic approaches in order to increase the probability of identifying truly secreted proteins with either a predicted enzymatic function or an as yet unknown function. An initial secretome of 970 proteins was predicted, whilst further stringent selection criteria predicted 492 proteins. Of these, 321 possess some functional annotation, the composition of which may reflect the strictly intercellular growth habit of this pathogen, leaving 171 with no functional annotation. This analysis identified a protein family encoding secreted peroxidases/chloroperoxidases (PF01328 which is expanded within all members of the family Mycosphaerellaceae. Further analyses were done on the non-annotated proteins for size and cysteine content (effector protein hallmarks, and then by studying the distribution of homologues in 17 other sequenced Dothideomycete fungi within an overall total of 91 predicted proteomes from fungal, oomycete and nematode species. This detailed M. graminicola secretome analysis provides the basis for further functional and comparative genomics studies.

  17. Characterization of the complete uric acid degradation pathway in the fungal pathogen Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    I Russel Lee

    Full Text Available Degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. In humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. Uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. In contrast, uric acid is completely degraded to ammonia in most fungi. Currently, relatively little is known about uric acid catabolism in the fungal pathogen Cryptococcus neoformans even though this yeast is commonly isolated from uric acid-rich pigeon guano. In addition, uric acid utilization enhances the production of the cryptococcal virulence factors capsule and urease, and may potentially modulate the host immune response during infection. Based on these important observations, we employed both Agrobacterium-mediated insertional mutagenesis and bioinformatics to predict all the uric acid catabolic enzyme-encoding genes in the H99 genome. The candidate C. neoformans uric acid catabolic genes identified were named: URO1 (urate oxidase, URO2 (HIU hydrolase, URO3 (OHCU decarboxylase, DAL1 (allantoinase, DAL2,3,3 (allantoicase-ureidoglycolate hydrolase fusion protein, and URE1 (urease. All six ORFs were then deleted via homologous recombination; assaying of the deletion mutants' ability to assimilate uric acid and its pathway intermediates as the sole nitrogen source validated their enzymatic functions. While Uro1, Uro2, Uro3, Dal1 and Dal2,3,3 were demonstrated to be dispensable for virulence, the significance of using a modified animal model system of cryptococcosis for improved mimicking of human pathogenicity is discussed.

  18. The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.

    Science.gov (United States)

    Leonhardt, Ines; Spielberg, Steffi; Weber, Michael; Albrecht-Eckardt, Daniela; Bläss, Markus; Claus, Ralf; Barz, Dagmar; Scherlach, Kirstin; Hertweck, Christian; Löffler, Jürgen; Hünniger, Kerstin; Kurzai, Oliver

    2015-03-17

    Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance. Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be

  19. Fungal osteomyelitis with vertebral re-ossification.

    Science.gov (United States)

    O Guinn, Devon J; Serletis, Demitre; Kazemi, Noojan

    2016-01-01

    We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Fungal biomass production from coffee pulp juice

    Energy Technology Data Exchange (ETDEWEB)

    De Leon, R.; Calzada, F.; Herrera, R.; Rolz, C.

    1980-01-01

    Coffee pulp or skin represents about 40% of the weight of the fresh coffee fruit. It is currently a waste and its improper handling creates serious pollution problems for coffee producing countries. Mechanical pressing of the pulp will produce two fractions: coffee pulp juice (CPJ) and pressed pulp. Aspergillus oryzae, Trichoderma harzianum, Penicillium crustosum and Gliocladium deliquescens grew well in supplemented CPJ. At shake flask level the optimum initial C/N ratio was found to be in the range of 8 to 14. At this scale, biomass values of up to 50 g/l were obtained in 24 hours. Biomass production and total sugar consumption were not significantly different to all fungal species tested at the bench-scale level, even when the initial C/N ratio was varied. Best nitrogen consumption values were obtained when the initial C/N ratio was 12. Maximum specific growth rates occurred between 4-12 hours for all fungal species tested. (Refs. 8).

  1. 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

  2. Burden of serious fungal infections in Mexico.

    Science.gov (United States)

    Corzo-León, D E; Armstrong-James, D; Denning, D W

    2015-10-01

    Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100,000) followed by allergic bronchopulmonary aspergillosis (60 per 100,000), chronic pulmonary aspergillosis (15.9 per 100,000), fungal keratitis (10.4 per 100,000), invasive candidiasis (8.6 per 100,000) and SFIs in HIV (8.2 per 100,000); coccidioidomycosis (7.6 per 100,000), IA (4.56 per 100,000). These correspond to 2,749,159 people affected in any year (2.45% of the population), probably >10,000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists. © 2015 Blackwell Verlag GmbH.

  3. Empirical support for optimal virulence in a castrating parasite.

    Directory of Open Access Journals (Sweden)

    Knut Helge Jensen

    2006-07-01

    Full Text Available The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times

  4. Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

    Directory of Open Access Journals (Sweden)

    Zhang X

    2018-01-01

    Full Text Available Xiaochen Zhang,1,* Quan Yu,2,* Yan-an Wang,1 Jun Zhao2 1Department of Oral and Maxillofacial-Head and Neck Oncology, 2Department of Orthodontics, College of Stomatology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China *These authors contributed equally to this work Introduction: To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2 are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods: A new growth factor delivery system was fabricated using BMP-2-loaded TiO2 nanotubes by lyophilization with trehalose (TiO2-Lyo-Tre-BMP-2. We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT, sequential fluorescent labelling, and histological analysis. Results: Compared with absorbed BMP-2-loaded TiO2 nanotubes (TiO2-BMP-2, TiO2-Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO2-Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO2-BMP-2 nanotubes. Conclusion: Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects. Keywords: bone morphogenetic protein-2, dose reduction, delivery system, trehalose, lyophilization, TiO2 nanotubes, BMP-2, regenerative medicine, surface

  5. Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions.

    Science.gov (United States)

    Krieger, John N; Thumbikat, Praveen

    2016-02-01

    Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.

  6. Screening of virulence genes in Staphylococcus aureus isolates from rabbits

    Directory of Open Access Journals (Sweden)

    David Viana Martín

    2015-09-01

    Full Text Available Staphylococcus aureus is a versatile pathogen able to cause disease in both humans and animals. In rabbits, this bacterium infects animals of different ages, producing several purulent lesions. The ability of S. aureus to cause disease depends on a combination of virulence factors. The aim of this study was therefore to investigate the distribution of bacterial virulence determinants in 69 S. aureus isolates from rabbits. Some virulence factors (7 adhesins, 1 toxin and 1 protease were positive in all rabbit S. aureus isolates analysed, while others (1 adhesin and 10 toxins were always negative. The remaining virulence factors were more variable among isolates. An association between genotype and the different profiles of virulence factors was observed, but not with the type of lesion (P<0.05. One strain of each genotype was further analysed by multilocus sequence typing, generating ST121, ST96 and ST2951, determining a greater number of enterotoxins in ST121 isolates compared to ST96 and ST2951 isolates, which could justify the different pathogenicity between strains. 

  7. Genetic Regulation of Virulence and Antibiotic Resistance in Acinetobacter baumannii

    Science.gov (United States)

    Kröger, Carsten; Kary, Stefani C.; Schauer, Kristina; Cameron, Andrew D. S.

    2016-01-01

    Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus Acinetobacter have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance. Here, we review current knowledge regarding the regulation of virulence genes and antibiotic resistance in Acinetobacter baumannii. A survey of the two-component systems AdeRS, BaeSR, GacSA and PmrAB explains how each contributes to antibiotic resistance and virulence gene expression, while BfmRS regulates cell envelope structures important for pathogen persistence. A. baumannii uses the transcription factors Fur and Zur to sense iron or zinc depletion and upregulate genes for metal scavenging as a critical survival tool in an animal host. Quorum sensing, nucleoid-associated proteins, and non-classical transcription factors such as AtfA and small regulatory RNAs are discussed in the context of virulence and antibiotic resistance. PMID:28036056

  8. Role of dupA in virulence of Helicobacter pylori.

    Science.gov (United States)

    Talebi Bezmin Abadi, Amin; Perez-Perez, Guillermo

    2016-12-14

    Helicobacter pylori ( H. pylori ) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori -associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a ( cagA ) and vacA , there are conflicting data about their actual participation as specific risk factor for H. pylori -related diseases. Duodenal ulcer promoting gene a ( dupA ) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.

  9. Molecular determinants of Ebola virus virulence in mice.

    Directory of Open Access Journals (Sweden)

    Hideki Ebihara

    2006-07-01

    Full Text Available Zaire ebolavirus (ZEBOV causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. The molecular basis for the extreme virulence of ZEBOV remains elusive. While adult mice resist ZEBOV infection, the Mayinga strain of the virus has been adapted to cause lethal infection in these animals. To understand the pathogenesis underlying the extreme virulence of Ebola virus (EBOV, here we identified the mutations responsible for the acquisition of the high virulence of the adapted Mayinga strain in mice, by using reverse genetics. We found that mutations in viral protein 24 and in the nucleoprotein were primarily responsible for the acquisition of high virulence. Moreover, the role of these proteins in virulence correlated with their ability to evade type I interferon-stimulated antiviral responses. These findings suggest a critical role for overcoming the interferon-induced antiviral state in the pathogenicity of EBOV and offer new insights into the pathogenesis of EBOV infection.

  10. The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus.

    Science.gov (United States)

    Hodille, Elisabeth; Rose, Warren; Diep, Binh An; Goutelle, Sylvain; Lina, Gerard; Dumitrescu, Oana

    2017-10-01

    Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease. Copyright © 2017 American Society for Microbiology.

  11. OrfX, a Nucleomodulin Required for Listeria monocytogenes Virulence

    Directory of Open Access Journals (Sweden)

    Andrzej Prokop

    2017-10-01

    Full Text Available Listeria monocytogenes is a bacterial pathogen causing severe foodborne infections in humans and animals. Listeria can enter into host cells and survive and multiply therein, due to an arsenal of virulence determinants encoded in different loci on the chromosome. Several key Listeria virulence genes are clustered in Listeria pathogenicity island 1. This important locus also contains orfX (lmo0206, a gene of unknown function. Here, we found that OrfX is a small, secreted protein whose expression is positively regulated by PrfA, the major transcriptional activator of Listeria virulence genes. We provide evidence that OrfX is a virulence factor that dampens the oxidative response of infected macrophages, which contributes to intracellular survival of bacteria. OrfX is targeted to the nucleus and interacts with the regulatory protein RybP. We show that in macrophages, the expression of OrfX decreases the level of RybP, which controls cellular infection. Collectively, these data reveal that Listeria targets RybP and evades macrophage oxidative stress for efficient infection. Altogether, OrfX is after LntA, the second virulence factor acting directly in the nucleus.

  12. Vacuolar zinc transporter Zrc1 is required for detoxification of excess intracellular zinc in the human fungal pathogen Cryptococcus neoformans.

    Science.gov (United States)

    Cho, Minsu; Hu, Guanggan; Caza, Mélissa; Horianopoulos, Linda C; Kronstad, James W; Jung, Won Hee

    2018-01-01

    Zinc is an important transition metal in all living organisms and is required for numerous biological processes. However, excess zinc can also be toxic to cells and cause cellular stress. In the model fungus Saccharomyces cerevisiae, a vacuolar zinc transporter, Zrc1, plays important roles in the storage and detoxification of excess intracellular zinc to protect the cell. In this study, we identified an ortholog of the S. cerevisiae ZRC1 gene in the human fungal pathogen Cryptococcus neoformans. Zrc1 was localized in the vacuolar membrane in C. neoformans, and a mutant lacking ZRC1 showed significant growth defects under high-zinc conditions. These results suggested a role for Zrc1 in zinc detoxification. However, contrary to our expectation, the expression of Zrc1 was induced in cells grown in zinc-limited conditions and decreased upon the addition of zinc. These expression patterns were similar to those of Zip1, the high-affinity zinc transporter in the plasma membrane of C. neoformans. Furthermore, we used the zrc1 mutant in a murine model of cryptococcosis to examine whether a mammalian host could inhibit the survival of C. neoformans using zinc toxicity. We found that the mutant showed no difference in virulence compared with the wildtype strain. This result suggests that Zrc1-mediated zinc detoxification is not required for the virulence of C. neoformans, and imply that zinc toxicity may not be an important aspect of the host immune response to the fungus.

  13. Physicochemical Properties of Fungal Detoxified Cassava Mash and ...

    African Journals Online (AJOL)

    The physicochemical properties of fungal detoxified cassava mash and sensory characteristics of wheat-detoxified cassava composite doughnuts were investigated. Fungal isolates from soils collected at cassava processing sites were isolated, quantified and identified. Cassava mash from grated tuber was partially ...

  14. The Top 10 fungal pathogens in molecular plant pathology

    NARCIS (Netherlands)

    Dean, R.; Kan, van J.A.L.; Pretorius, Z.A.; Hammond-Kosack, K.E.; Pietro, Di A.; Spanu, P.D.; Rudd, J.J.; Dickman, M.; Kahmann, R.; Ellis, J.; Foster, G.D.

    2012-01-01

    The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a ‘Top 10’ based on scientific/economic importance. The survey generated 495 votes from the international

  15. Chronic invasive fungal granulomatous rhino-sinusitis: a case report ...

    African Journals Online (AJOL)

    Fungal Rhino-Sinusitis (FRS) is a relatively uncommon entity. The chronic invasive granulomatous form of FRS (FGRS) is a slowly progressive form of fungal infection characterized by chronic granulomatous process with a time course of longer than 12 weeks. The aim of this report is to draw the attention of colleagues to ...

  16. Structure and biosynthesis of fungal alpha-glucans

    NARCIS (Netherlands)

    Grün, Christian Hugo

    2003-01-01

    The fungal cell wall is unique among eukaryotes and therefore it forms an ideal target for the development of novel antifungal drugs. Fungal cell morphology and integrity depend on a cell-surrounding wall, which is composed of glycoproteins and polysaccharides. Disrupting enzymes that are involved

  17. First genomic survey of human skin fungal diversity

    Science.gov (United States)

    Fungal infections of the skin affect 29 million people in the United States. In the first study of human fungal skin diversity, National Institutes of Health researchers sequenced the DNA of fungi that thrive at different skin sites of healthy adults to d

  18. Studies on the fungal flora of Garri, processed cassava ( Manihot ...

    African Journals Online (AJOL)

    In Nsukka area of southeastern Nigeria, garri is usually displayed in the open market for sale which no doubt exposes the food stuff to dust particles from moving vehicles, wind and other sources. Thus, fungal spores from the air and soil environment could serve as major sources of fungal contamination of this product.

  19. Isolation and identification of fungal species from dried date palm ...

    African Journals Online (AJOL)

    A total of 360 dried date palm (Phoenix dactylifera) fruits were collected from hawkers, shops and market places within Maiduguri metropolis for the detection of the presence of fungal species. Investigation was based on cultural, microscopically and biochemical tests. Of the 327 (90.83%) fungal isolates recovered on ...

  20. Production of Microbial Protease from Selected Soil Fungal Isolates ...

    African Journals Online (AJOL)

    Production of Microbial Protease from Selected Soil Fungal Isolates. ... Nigerian Journal of Biotechnology ... and 500C. The optimal pH on the enzyme production was observed to be between pH 3.5 and 5.5 for the organisms. Keywords: Soil microorganism, fungal isolate, incubation period, microbial enzyme. Nig J. Biotech.