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Sample records for antibacterial host defense

  1. Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis.

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    Stella E Autenrieth

    2012-02-01

    Full Text Available Dendritic cells (DCs as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye. We used CD11c-diphtheria toxin (DT mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection.

  2. A fossil antibacterial peptide gives clues to structural diversity of cathelicidin-derived host defense peptides.

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    Zhu, Shunyi; Gao, Bin

    2009-01-01

    Cathelicidins, a group of vertebrate- specific immune effector molecules, developed into a multigene family through gene duplication in the Cetartiodactyla lineage, in which structural changes of the antimicrobial domains (AMDs) among paralogs during evolution are clearly associated with functional diversification of cathelicidins. However, the evolutionary mechanism for such structural diversity remains largely unsolved. Although at the genomic level, the 3'-exon alone encoding the variable AMD repertoire would favor a role of exon shuffling, the observation that two structurally unrelated subfamilies of AMDs (protegrins and prophenins) display high similarity in some nucleotide regions of the 3'-exons of their genes provides evidence for postduplication sequence remodeling. This opinion is further strengthened by finding a proline-arginine-rich antibacterial peptide of 38 residues (named PR-38) encoded by an open reading frame located in the 3' untranslated region of protegrins, which is in frame with prophenins. The latter appears to have undergone internal motif repeats in the region corresponding to PR-38. PR-38 exhibits similar amino acid sequence and carboxyl-terminal amidation feature to PR-39s, a subfamily of cathelicidin peptides conserved across Cetartiodactyla. Functional assays of the chemically synthesized PR-38 confirmed its antibacterial activity with a similar action mode to PR-39 against both gram-positive and gram-negative bacteria at micromolar concentrations, supporting an ancient functional link among cathelicidin members belonging to different subfamilies. Resurrecting the fossil peptide highlights the evolutionary position of PR-39 in generating structurally variable subfamilies of porcine cathelicidins through postduplication sequence remodeling. PMID:18796560

  3. The Inflammasome in Host Defense

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    Gang Chen

    2009-12-01

    Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

  4. A Diverse Family of Host-Defense Peptides (Piscidins) Exhibit Specialized Anti-Bacterial and Anti-Protozoal Activities in Fishes.

    Science.gov (United States)

    Salger, Scott A; Cassady, Katherine R; Reading, Benjamin J; Noga, Edward J

    2016-01-01

    Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, α-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis). In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology) and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3) show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7) primarily show anti-protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5) have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture. PMID:27552222

  5. Carp erythrodermatitis: host defense-pathogen interaction.

    OpenAIRE

    Pourreau, C.N.

    1990-01-01

    The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the host's defense system. On the other hand, the host's resistance to a bacterial attack depends on its physiological state, the intensity of the bacterial attack and the efficacy of the defense system to neutralize toxins a...

  6. Carp erythrodermatitis: host defense-pathogen interaction.

    NARCIS (Netherlands)

    Pourreau, C.N.

    1990-01-01

    The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the host's defense syste

  7. The lactoperoxidase system links anion transport to host defense in cystic fibrosis.

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    Conner, Gregory E; Wijkstrom-Frei, Corinne; Randell, Scott H; Fernandez, Vania E; Salathe, Matthias

    2007-01-23

    Chronic respiratory infections in cystic fibrosis result from CFTR channel mutations but how these impair antibacterial defense is less clear. Airway host defense depends on lactoperoxidase (LPO) that requires thiocyanate (SCN-) to function and epithelia use CFTR to concentrate SCN- at the apical surface. To test whether CFTR mutations result in impaired LPO-mediated host defense, CF epithelial SCN- transport was measured. CF epithelia had significantly lower transport rates and did not accumulate SCN- in the apical compartment. The lower CF [SCN-] did not support LPO antibacterial activity. Modeling of airway LPO activity suggested that reduced transport impairs LPO-mediated defense and cannot be compensated by LPO or H2O2 upregulation.

  8. Hepcidin and Host Defense against Infectious Diseases

    OpenAIRE

    Michels, Kathryn; Nemeth, Elizabeta; Ganz, Tomas; Mehrad, Borna

    2015-01-01

    Hepcidin is the master regulator of iron homeostasis in vertebrates. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. While the role of hepcidin in iron regulation is well established, its contribution to host defense is emerging as complex and multifaceted. In this review, we summarize the literature on the role of hepcidin as a mediator of antimicrobial immunity. Hepcidin induction during infection causes depletion of extracellular iron, which is tho...

  9. Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications

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    Guolong Zhang

    2014-02-01

    Full Text Available Host defense peptides (HDPs are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens.

  10. Host defense and hepatic metallothionein induction

    International Nuclear Information System (INIS)

    This is a brief review of my investigations to search a mechanism of the promotion of radioresistance in mice regarding the activation of host defense mechanism which seems to involve chemical as well as immunological protections. Intraperitoneal (i.p.) injection of a metal salt: MnCl2 (10mg Mn/kg) or of a biological response modifier (BRM): IL-1 (40 μg/kg) or OK432 (15mg/kg), or Chinese herbal medicine, Toki (270mg/kg) or Shigoka (250mg/kg), one day prior to 7.5 Gy of X-ray irradiation produced prominent radioprotection in mice. While i.p. injection of MgCl2 (10mg/kg), or PS-K (50mg/kg) or Lentinan (5mg/kg) showed none. The obtained dose reduction factor (DRF) was 1.2 - 1.3. Pretreated mice in which more than 4 or 5 times of hepatic metallothionein (MT) synthesis of the control level was observed showed prominent radioresistance, while pretreated mice in which hepatic MT induction was less than 3 times of the control showed no promotion of radioresistance. The administration of MnCl2, CdCl2, OK432 or Toki as well as skin excision, caused enhancement in superoxide anion production (SOA) in peripheral leukocytes measured by chemiluminescence response, which was due to an increase in the number of polymorphonuclear leukocytes (PMN). The increase in SOA in peripheral leukocytes and hepatic MT synthesis occurred almost concomitantly. The degree of radioresistance was also consistent with peripheral blood corpuscle counts measured on the 10th and 15th postirradiation days. We, therefore, speculate that the enhancement of radioresistance by the preirradiation treatment with a certain metal and/or BRM or stressful load might be established by a coordinating promotion between chemical and immunological protection mechanisms. (author)

  11. Host defense reinforces host–parasite cospeciation

    OpenAIRE

    Clayton, Dale H.; Bush, Sarah E.; Goates, Brad M.; Johnson, Kevin P.

    2003-01-01

    Cospeciation occurs when interacting groups, such as hosts and parasites, speciate in tandem, generating congruent phylogenies. Cospeciation can be a neutral process in which parasites speciate merely because they are isolated on diverging host islands. Adaptive evolution may also play a role, but this has seldom been tested. We explored the adaptive basis of cospeciation by using a model system consisting of feather lice (Columbicola) and their pigeon and dove hosts (Columbiformes). We recon...

  12. Insights from human studies into the host defense against candidiasis.

    Science.gov (United States)

    Filler, Scott G

    2012-04-01

    Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections.

  13. Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology

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    Suresh, Rahul; Mosser, David M.

    2013-01-01

    Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.…

  14. The host defense proteome of human and bovine milk.

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    Kasper Hettinga

    Full Text Available Milk is the single source of nutrients for the newborn mammal. The composition of milk of different mammals has been adapted during evolution of the species to fulfill the needs of the offspring. Milk not only provides nutrients, but it also serves as a medium for transfer of host defense components to the offspring. The host defense proteins in the milk of different mammalian species are expected to reveal signatures of evolution. The aim of this study is therefore to study the difference in the host defense proteome of human and bovine milk. We analyzed human and bovine milk using a shot-gun proteomics approach focusing on host defense-related proteins. In total, 268 proteins in human milk and 269 proteins in bovine milk were identified. Of these, 44 from human milk and 51 from bovine milk are related to the host defense system. Of these proteins, 33 were found in both species but with significantly different quantities. High concentrations of proteins involved in the mucosal immune system, immunoglobulin A, CD14, lactoferrin, and lysozyme, were present in human milk. The human newborn is known to be deficient for at least two of these proteins (immunoglobulin A and CD14. On the other hand, antimicrobial proteins (5 cathelicidins and lactoperoxidase were abundant in bovine milk. The high concentration of lactoperoxidase is probably linked to the high amount of thiocyanate in the plant-based diet of cows. This first detailed analysis of host defense proteins in human and bovine milk is an important step in understanding the function of milk in the development of the immune system of these two mammals.

  15. The Host Defense Proteome of Human and Bovine Milk

    NARCIS (Netherlands)

    Hettinga, K.A.; Valenberg, van H.J.F.; Vries, de S.C.; Boeren, S.; Hooijdonk, van A.C.M.; Arendonk, van J.A.M.; Vervoort, J.J.M.

    2011-01-01

    Milk is the single source of nutrients for the newborn mammal. The composition of milk of different mammals has been adapted during evolution of the species to fulfill the needs of the offspring. Milk not only provides nutrients, but it also serves as a medium for transfer of host defense components

  16. Crossing the Rubicon: New Roads Lead to Host Defense

    OpenAIRE

    Bradfield, Clinton J.; Kim, Bae-Hoon; MacMicking, John D.

    2012-01-01

    Rubicon is a protein known to engage the Beclin-1/Vps34-PI3K/UVRAG complex and inhibit endosome and autophagosomal fusion with lysosomes. Yang et al. (2012) uncover new roles for this adaptor protein within noncanonical p22phox or CARD9 complexes that regulate oxidative and cytokine responses in activated macrophages, respectively. Both complexes impact pathogen-specific host defense.

  17. Toll-Like Receptor Initiated Host Defense against Toxoplasma gondii

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    Eric Y. Denkers

    2010-01-01

    Full Text Available Toxoplasma gondii is an intracellular pathogen notable for its ability to establish a stable host-parasite relationship amongst a wide range of host species and in a large percentage of the human population. Toll-like receptor signaling through MyD88 is a critical pathway in initiating defense against this opportunistic protozoan and may also be a mediator of pathology during immune dysfunction. Other MyD88 independent signaling pathways are also involved in the host-parasite interaction. These responses can be triggered by the parasite itself, but interactions with the intestinal microbiota add additional complexity during enteric infection.

  18. Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

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    Wy Ching Ng

    2012-01-01

    Full Text Available Host defenses against viral infections depend on a complex interplay of innate (nonspecific and adaptive (specific components. In the early stages of infection, innate mechanisms represent the main line of host defense, acting to limit the spread of virus in host tissues prior to the induction of the adaptive immune response. Serum and lung fluids contain a range of lectins capable of recognizing and destroying influenza A viruses (IAV. Herein, we review the mechanisms by which soluble endogenous lectins mediate anti-IAV activity, including their role in modulating IAV-induced inflammation and disease and their potential as prophylactic and/or therapeutic treatments during severe IAV-induced disease.

  19. The roles of antimicrobial peptides in innate host defense.

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    Diamond, Gill; Beckloff, Nicholas; Weinberg, Aaron; Kisich, Kevin O

    2009-01-01

    Antimicrobial peptides (AMPs) are multi-functional peptides whose fundamental biological role in vivo has been proposed to be the elimination of pathogenic microorganisms, including Gram-positive and -negative bacteria, fungi, and viruses. Genes encoding these peptides are expressed in a variety of cells in the host, including circulating phagocytic cells and mucosal epithelial cells, demonstrating a wide range of utility in the innate immune system. Expression of these genes is tightly regulated; they are induced by pathogens and cytokines as part of the host defense response, and they can be suppressed by bacterial virulence factors and environmental factors which can lead to increased susceptibility to infection. New research has also cast light on alternative functionalities, including immunomodulatory activities, which are related to their unique structural characteristics. These peptides represent not only an important component of innate host defense against microbial colonization and a link between innate and adaptive immunity, but also form a foundation for the development of new therapeutic agents.

  20. Airway acidification initiates host defense abnormalities in cystic fibrosis mice

    Science.gov (United States)

    Shah, Viral S.; Meyerholz, David K.; Tang, Xiao Xiao; Reznikov, Leah; Alaiwa, Mahmoud Abou; Ernst, Sarah E.; Karp, Philip H.; Wohlford-Lenane, Christine L.; Heilmann, Kristopher P.; Leidinger, Mariah R.; Allen, Patrick D.; Zabner, Joseph; McCray, Paul B.; Ostedgaard, Lynda S.; Stoltz, David A.; Randak, Christoph O.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  1. Interleukin 17-Mediated Host Defense against Candida albicans

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    Florian Sparber

    2015-08-01

    Full Text Available Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic mucocutaneous candidiasis led to the identification of interleukin-17 (IL-17 as a key factor in host defense against mucosal fungal infection. Experimental infections in mice confirmed the critical role of IL-17 in mucocutaneous immunity against C. albicans. Research on mouse models has also contributed importantly to our current understanding of the regulation of IL-17 production by different cellular sources and its effector functions in distinct tissues. In this review, we highlight recent findings on IL-17-mediated immunity against C. albicans in mouse and man.

  2. NOD1-Mediated Mucosal Host Defense against Helicobacter pylori

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    Tomohiro Watanabe

    2010-01-01

    Full Text Available Infection of the stomach with Helicobacter pylori is an important risk factor for gastritis, peptic ulcer, and gastric carcinoma. Although it has been well established that persistent colonization by H. pylori is associated with adaptive Th1 responses, the innate immune responses leading to these Th1 responses are poorly defined. Recent studies have shown that the activation of nucleotide-binding oligomerization domain 1 (NOD1 in gastric epithelial cells plays an important role in innate immune responses against H. pylori. The detection of H. pylori-derived ligands by cytosolic NOD1 induces several host defense factors, including antimicrobial peptides, cytokines, and chemokines. In this paper, we review the molecular mechanisms by which NOD1 contributes to mucosal host defense against H. pylori infection of the stomach.

  3. Insights from human studies into the host defense against candidiasis

    OpenAIRE

    Filler, Scott G

    2011-01-01

    Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is crit...

  4. Green tea consumption after intense taekwondo training enhances salivary defense factors and antibacterial capacity.

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    Shiuan-Pey Lin

    Full Text Available The aim of this study was to investigate the short-term effects of green tea consumption on selected salivary defense proteins, antibacterial capacity and anti-oxidation activity in taekwondo (TKD athletes, following intensive training. Twenty-two TKD athletes performed a 2-hr TKD training session. After training, participants ingested green tea (T, caffeine 6 mg/kg and catechins 22 mg/kg or an equal volume of water (W. Saliva samples were collected at three time points: before training (BT-T; BT-W, immediately after training (AT-T; AT-W, and 30 min after drinking green tea or water (Rec-T; Rec-W. Salivary total protein, immunoglobulin A (SIgA, lactoferrin, α-amylase activity, free radical scavenger activity (FRSA and antibacterial capacity were measured. Salivary total protein, lactoferrin, SIgA concentrations and α-amylase activity increased significantly immediately after intensive TKD training. After tea drinking and 30 min rest, α-amylase activity and the ratio of α-amylase to total protein were significantly higher than before and after training. In addition, salivary antibacterial capacity was not affected by intense training, but green tea consumption after training enhanced salivary antibacterial capacity. Additionally, we observed that salivary FRSA was markedly suppressed immediately after training and quickly returned to pre-exercise values, regardless of which fluid was consumed. Our results show that green tea consumption significantly enhances the activity of α-amylase and salivary antibacterial capacity.

  5. Host Defense Peptides from Asian Frogs as Potential Clinical Therapies

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    Vineeth T.V. Kumar

    2015-03-01

    Full Text Available Host defense peptides (HDPs are currently major focal points of medical research as infectious microbes are gaining resistance to existing drugs. They are effective against multi-drug resistant pathogens due to their unique primary target, biological membranes, and their peculiar mode of action. Even though HDPs from 60 Asian frog species belonging to 15 genera have been characterized, research into these peptides is at a very early stage. The purpose of this review is to showcase the status of peptide research in Asia. Here we provide a summary of HDPs from Asian frogs.

  6. Functions of antimicrobial peptides in host defense and immunity.

    Science.gov (United States)

    Beisswenger, Christoph; Bals, Robert

    2005-06-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Besides their direct antimicrobial function, they have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis, immune induction, and protease-antiprotease balance. Furthermore, AMPs qualify as prototypes of innovative drugs that may be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation. This review summarizes the current knowledge about the basic and applied biology of antimicrobial peptides and discusses features of AMPs in host defense and inflammation.

  7. Necroptosis: The Trojan horse in cell autonomous antiviral host defense.

    Science.gov (United States)

    Mocarski, Edward S; Guo, Hongyan; Kaiser, William J

    2015-05-01

    Herpesviruses suppress cell death to assure sustained infection in their natural hosts. Murine cytomegalovirus (MCMV) encodes suppressors of apoptosis as well as M45-encoded viral inhibitor of RIP activation (vIRA) to block RIP homotypic interaction motif (RHIM)-signaling and recruitment of RIP3 (also called RIPK3), to prevent necroptosis. MCMV and human cytomegalovirus encode a viral inhibitor of caspase (Casp)8 activation to block apoptosis, an activity that unleashes necroptosis. Herpes simplex virus (HSV)1 and HSV2 incorporate both RHIM and Casp8 suppression strategies within UL39-encoded ICP6 and ICP10, respectively, which are herpesvirus-conserved homologs of MCMV M45. Both HSV proteins sensitize human cells to necroptosis by blocking Casp8 activity while preventing RHIM-dependent RIP3 activation and death. In mouse cells, HSV1 ICP6 interacts with RIP3 and, surprisingly, drives necroptosis. Thus, herpesviruses have illuminated the contribution of necoptosis to host defense in the natural host as well as its potential to restrict cross-species infections in nonnatural hosts. PMID:25819165

  8. Characterization of a proteolytically stable multifunctional host defense peptidomimetic

    DEFF Research Database (Denmark)

    Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik;

    2013-01-01

    The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentra......The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory......-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition......, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α....

  9. Epithelial antimicrobial peptides in host defense against infection

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    Bals Robert

    2000-10-01

    Full Text Available Abstract One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation.

  10. Green Tea Consumption after Intense Taekwondo Training Enhances Salivary Defense Factors and Antibacterial Capacity

    OpenAIRE

    Lin, Shiuan-Pey; Li, Chia-Yang; Suzuki, Katsuhiko; Chang, Chen-Kang; Chou, Kuei-Ming; Fang, Shih-Hua

    2014-01-01

    The aim of this study was to investigate the short-term effects of green tea consumption on selected salivary defense proteins, antibacterial capacity and anti-oxidation activity in taekwondo (TKD) athletes, following intensive training. Twenty-two TKD athletes performed a 2-hr TKD training session. After training, participants ingested green tea (T, caffeine 6 mg/kg and catechins 22 mg/kg) or an equal volume of water (W). Saliva samples were collected at three time points: before training (B...

  11. Addicted? Reduced host resistance in populations with defensive symbionts.

    Science.gov (United States)

    Martinez, Julien; Cogni, Rodrigo; Cao, Chuan; Smith, Sophie; Illingworth, Christopher J R; Jiggins, Francis M

    2016-06-29

    Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing Drosophila melanogaster populations to infection with the pathogenic Drosophila C virus (DCV) in the presence or absence of Wolbachia, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of Wolbachia the resistant allele of pastrel-a gene that has a major effect on resistance to DCV-was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens. PMID:27335421

  12. Addicted? Reduced host resistance in populations with defensive symbionts

    Science.gov (United States)

    Cogni, Rodrigo; Cao, Chuan; Smith, Sophie; Illingworth, Christopher J. R.; Jiggins, Francis M.

    2016-01-01

    Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing Drosophila melanogaster populations to infection with the pathogenic Drosophila C virus (DCV) in the presence or absence of Wolbachia, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of Wolbachia the resistant allele of pastrel—a gene that has a major effect on resistance to DCV—was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens. PMID:27335421

  13. Host defense mechanism-based rational design of live vaccine.

    Directory of Open Access Journals (Sweden)

    Yo Han Jang

    Full Text Available Live attenuated vaccine (LAV, mimicking natural infection, provides an excellent protection against microbial infection. The development of LAV, however, still remains highly empirical and the rational design of clinically useful LAV is scarcely available. Apoptosis and caspase activation are general host antiviral responses in virus-infected cells. Utilizing these tightly regulated host defense mechanisms, we present a novel apoptosis-triggered attenuation of viral virulence as a rational design of live attenuated vaccine with desired levels of safety, efficacy, and productivity. Mutant influenza viruses carrying caspase recognition motifs in viral NP and the interferon-antagonist NS1 proteins were highly attenuated both in vitro and in vivo by caspase-mediated cleavage of those proteins in infected cells. Both viral replication and interferon-resistance were substantially reduced, resulting in a marked attenuation of virulence of the virus. Despite pronounced attenuation, the viruses demonstrated high growth phenotype in embryonated eggs at lower temperature, ensuring its productivity. A single dose vaccination with the mutant virus elicited high levels of systemic and mucosal antibody responses and provided complete protection against both homologous and heterologous lethal challenges in mouse model. While providing a practical means to generate seasonal or pandemic influenza live vaccines, the sensitization of viral proteins to pathogen-triggered apoptotic signals presents a potentially universal, mechanism-based rational design of live vaccines against many viral infections.

  14. Host defense mechanism-based rational design of live vaccine.

    Science.gov (United States)

    Jang, Yo Han; Byun, Young Ho; Lee, Kwang-Hee; Park, Eun-Sook; Lee, Yun Ha; Lee, Yoon-Jae; Lee, Jinhee; Kim, Kyun-Hwan; Seong, Baik Lin

    2013-01-01

    Live attenuated vaccine (LAV), mimicking natural infection, provides an excellent protection against microbial infection. The development of LAV, however, still remains highly empirical and the rational design of clinically useful LAV is scarcely available. Apoptosis and caspase activation are general host antiviral responses in virus-infected cells. Utilizing these tightly regulated host defense mechanisms, we present a novel apoptosis-triggered attenuation of viral virulence as a rational design of live attenuated vaccine with desired levels of safety, efficacy, and productivity. Mutant influenza viruses carrying caspase recognition motifs in viral NP and the interferon-antagonist NS1 proteins were highly attenuated both in vitro and in vivo by caspase-mediated cleavage of those proteins in infected cells. Both viral replication and interferon-resistance were substantially reduced, resulting in a marked attenuation of virulence of the virus. Despite pronounced attenuation, the viruses demonstrated high growth phenotype in embryonated eggs at lower temperature, ensuring its productivity. A single dose vaccination with the mutant virus elicited high levels of systemic and mucosal antibody responses and provided complete protection against both homologous and heterologous lethal challenges in mouse model. While providing a practical means to generate seasonal or pandemic influenza live vaccines, the sensitization of viral proteins to pathogen-triggered apoptotic signals presents a potentially universal, mechanism-based rational design of live vaccines against many viral infections.

  15. Granzyme A impairs host defense during Streptococcus pneumoniae pneumonia.

    Science.gov (United States)

    van den Boogaard, Florry E; van Gisbergen, Klaas P J M; Vernooy, Juanita H; Medema, Jan P; Roelofs, Joris J T H; van Zoelen, Marieke A D; Endeman, Henrik; Biesma, Douwe H; Boon, Louis; Van't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2016-08-01

    Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia (CAP). Granzyme A (GzmA) is a serine protease produced by a variety of cell types involved in the immune response. We sought to determine the role of GzmA on the host response during pneumococcal pneumonia. GzmA was measured in bronchoalveolar lavage fluid (BALF) harvested from CAP patients from the infected and contralateral uninfected side and in lung tissue slides from CAP patients and controls. In CAP patients, GzmA levels were increased in BALF obtained from the infected lung. Human lungs showed constitutive GzmA expression by both parenchymal and nonparenchymal cells. In an experimental setting, pneumonia was induced in wild-type (WT) and GzmA-deficient (GzmA(-/-)) mice by intranasal inoculation of S. pneumoniae In separate experiments, WT and GzmA(-/-) mice were treated with natural killer (NK) cell depleting antibodies. Upon infection with S. pneumoniae, GzmA(-/-) mice showed a better survival and lower bacterial counts in BALF and distant body sites compared with WT mice. Although NK cells showed strong GzmA expression, NK cell depletion did not influence bacterial loads in either WT or GzmA(-/-) mice. These results implicate that GzmA plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on NK cells. PMID:27343190

  16. Immune regulatory activities of fowlicidin-1, a cathelicidin host defense peptide.

    Science.gov (United States)

    Bommineni, Yugendar R; Pham, Giang H; Sunkara, Lakshmi T; Achanta, Mallika; Zhang, Guolong

    2014-05-01

    Appropriate modulation of immunity is beneficial in antimicrobial therapy and vaccine development. Host defense peptides (HDPs) constitute critically important components of innate immunity with both antimicrobial and immune regulatory activities. We previously showed that a chicken HDP, namely fowlicidin-1(6-26), has potent antibacterial activities in vitro and in vivo. Here we further revealed that fowl-1(6-26) possesses strong immunomodulatory properties. The peptide is chemotactic specifically to neutrophils, but not monocytes or lymphocytes, after injected into the mouse peritoneum. Fowl-1(6-26) also has the capacity to activate macrophages by inducing the expression of inflammatory mediators including IL-1β, CCL2, and CCL3. However, unlike bacterial lipopolysaccharide that triggers massive production of inflammatory cytokines and chemokines, fowl-1(6-26) only marginally increased their expression in mouse RAW264.7 macrophages. Additionally, fowl-1(6-26) enhanced the surface expression of MHC II and CD86 on RAW264.7 cells, suggesting that it may facilitate development of adaptive immune response. Indeed, co-immunization of mice with chicken ovalbumin (OVA) and fowl-1(6-26) augmented both OVA-specific IgG1 and IgG2a titers, relative to OVA alone. We further showed that fowl-1(6-26) is capable of preventing a methicillin-resistant Staphylococcus aureus (MRSA) infection due to its enhancement of host defense. All mice survived from an otherwise lethal infection when the peptide was administered 1-2 days prior to MRSA infection, and 50% mice were protected if receiving the peptide 4 days before infection. Taken together, with a strong capacity to stimulate innate and adaptive immunity, fowl-1(6-26) may have potential to be developed as a novel antimicrobial and a vaccine adjuvant.

  17. Autophagy is redundant for the host defense against systemic Candida albicans infections

    NARCIS (Netherlands)

    Smeekens, S.P.; Malireddi, R.K.; Plantinga, T.S.; Buffen, K.; Oosting, M.; Joosten, L.A.B.; Kullberg, B.J.; Perfect, J.R.; Scott, W.K.; Veerdonk, F.L. van de; Xavier, R.J.; Vosse, E. van de; Kanneganti, T.D.; Johnson, M.D.; Netea, M.G.

    2014-01-01

    Autophagy has been demonstrated to play an important role in the immunity against intracellular pathogens, but very little is known about its role in the host defense against fungal pathogens such as Candida albicans. Therefore, the role of autophagy for the host defense against C. albicans was asse

  18. GENES, IN ADDITION TO TOLL-LIKE RECEPTOR 2, PLAY A ROLE IN ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL PNEUMONIA

    Science.gov (United States)

    Streptococcus infection in human populations continues to be a major cause of morbidity and mortality. To evaluate the effect of genetic background and toll-like receptor 2 (TLR2) on antibacterial defense to streptococcal infection, eight genetically diverse strains of mic...

  19. Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.

    Directory of Open Access Journals (Sweden)

    Miriam H P van Lieshout

    2014-09-01

    Full Text Available Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88(-/- and myeloid plus endothelial (Tie2-Myd88(-/- cells showed enhanced lethality and bacterial growth. Tie2-Myd88(-/- mice reconstituted with control bone marrow, representing mice with a selective MyD88 deficiency in endothelial cells, showed an unremarkable antibacterial defense. Myeloid or endothelial cell MyD88 deficiency did not impact on lung pathology or distant organ injury during late stage sepsis, while LysM-Myd88(-/- mice demonstrated a strongly attenuated inflammatory response in the airways early after infection. These data suggest that myeloid but not endothelial MyD88 is important for host defense during gram-negative pneumonia derived sepsis.

  20. The effect of chronic exposure to tobacco smoke on the antibacterial defenses of the lung.

    Science.gov (United States)

    Huber, G L; Pochay, V E; Mahajan, V K; McCarthy, C R; Hinds, W C; Davies, P; Drath, D B; Sornberger, G C

    1977-01-01

    To evaluate the effects of cigarette smoking on the host defenses of the lung, male CD rats were exposed to fresh whole smoke for up to 60 consecutive days. Intrapulmonary deposition of smoke and animal exposure levels, quantified with decachlorobiphenyl and other smoke tracers, indicated a daily cigarette exposure equivalent to approximately a pack and a half per day in man. Pulmonary alveolar macrophage function in situ was quantified by the inactivation of an aerosolized challenge of Staphylococcus aureus six hours after inoculation. Controls (n=120) inactivated 88.8+/-0.64% of the staphylococci. Exposure to whole smoke did not impair intrapulmonary antistaphylococcal defenses, with inactivation rates of 89.8+/-0.97% (n=49) and 89.1+/-0.46% (n=74) at 30 and 60 days, respectively. Inactivation distribution frequency analysis in controls revealed that 7% of animals had inactivation values greater than two standard deviations from the mean. With prolonged exposure mean with less skewing towards the abnormal. Alveolar macrophages harvested from smoked animals were comparable in viability and in vitro antistaphylococcal activity to controls, appeared to be metabolically activated and had specific stereologic ultrastructural alterations. These studies indicate that chronic exposure to tobacco smoke does not impair, and in fact may stimulate, the host defenses of the lung, as evaluated by in vivo and in vitro pulmonary alveolar macrophage function. PMID:843645

  1. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of action....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism of action

  2. Host defense peptides and their antimicrobial-immunomodulatory duality.

    Science.gov (United States)

    Steinstraesser, Lars; Kraneburg, Ursula; Jacobsen, Frank; Al-Benna, Sammy

    2011-03-01

    Host defence peptides (HDPs) are short cationic molecules produced by the immune systems of most multicellular organisms and play a central role as effector molecules of innate immunity. Host defence peptides have a wide range of biological activities from direct killing of invading pathogens to modulation of immunity and other biological responses of the host. HDPs have important functions in multiple, clinically relevant disease processes and their imbalanced expression is associated with pathology in different organ systems and cell types. Furthermore, HDPs are now evaluated as model molecules for the development of novel natural antibiotics and immunoregulatory compounds. This review provides an overview of HDPs focused on their antimicrobial-immunomodulatory duality.

  3. The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity.

    Science.gov (United States)

    Yang, D; Chertov, O; Oppenheim, J J

    2001-06-01

    Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms. The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses. The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37). The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules. They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin. In contrast, C5a and C3b are produced by activation of the serum complement cascade. The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces. The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet. The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects. Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation.

  4. Modification of FMDV anti-host defense mechanism

    OpenAIRE

    Guan, Suhua; Belsham, Graham

    2014-01-01

    Foot-and-mouth disease virus (FMDV) is the etiologic agent of FMD, an infectious and sometimes fatal viral disease that affects cloven-hoofed animals. The FMDV genome encodes a large polyprotein, the first component of which is the Leader protein. Unusually, within the picornavirus family, the FMDV Leader protein (Lpro) is a protease. This protease induces a very rapid inhibition of host cell cap-dependent protein synthesis within infected cells. This results from cleavage of the cellular tra...

  5. Modification of FMDV anti-host defense mechanism

    DEFF Research Database (Denmark)

    Guan, Suhua; Belsham, Graham

    Foot-and-mouth disease virus (FMDV) is the etiologic agent of FMD, an infectious and sometimes fatal viral disease that affects cloven-hoofed animals. The FMDV genome encodes a large polyprotein, the first component of which is the Leader protein. Unusually, within the picornavirus family, the FM...... allow design of mutant viruses that are deficient in blocking host cell responses to infection (e.g. interferon induction) and assist in the rational design of antiviral agents targeting this process....

  6. Candida Infections: An Update on Host Immune Defenses and Anti-Fungal Drugs

    Directory of Open Access Journals (Sweden)

    Ning Gao

    2016-04-01

    Full Text Available Infections by fungal pathogens such as Candida albicans and non-albicans Candida species are becoming increasing prevalent in the human population. Such pathogens cause life-threatening diseases with high mortality, particularly in immunocompromised patients. Host defenses against fungal infections are provided by an exquisite interplay between innate and adaptive immune responses. However, effective anti-fungal agents for Candida infections are limited, and fungal drug resistance is a significant treatment challenge. In this review, we summarize the current understanding of host–fungal interactions, discuss the modes action of anti-fungal drugs, explore host defense mechanisms, and define the new challenges for treating Candida infections.

  7. Diverse Functions of Pulmonary Collectins in Host Defense of the Lung

    OpenAIRE

    Yoshio Kuroki; Chiaki Nishitani; Shigeru Ariki

    2012-01-01

    Pulmonary surfactant is a mixture of lipids and proteins that covers alveolar surfaces and keeps alveoli from collapsing. Four specific proteins have been identified in surfactant. Among them, two C-type lectins, surfactant proteins A and D (SP-A and SP-D), are known to be implicated in host defense and regulation of inflammatory responses of the lung. These host defense lectins are structurally characterized by N-terminal collagen-like domains and lectin domains and are called pulmonary coll...

  8. Symbiotic Bacteria Enable Olive Fly Larvae to Overcome Host Defenses

    International Nuclear Information System (INIS)

    Ripe fruit offer readily available nutrients for many animals, including fruit fly larvae (Diptera: Tephritidae) and their associated rot-inducing bacteria. Yet, during most of their ontogeny, fruit remain chemically defended and effectively suppress herbivores and pathogens by high levels of secondary metabolites. Olive flies (Bactrocera oleae) are uniquely able to develop in unripe olives. Unlike other frugivorous tephritids, the larvae maintain bacteria confined within their midgut caeca. We examined the interaction between larvae, their associated bacteria, and fruit chemical defence, hypothesizing that bacterial contribution to larval development is contingent on the phenology of fruit defensive chemistry. We demonstrate that larvae require their natural complement of bacteria (Candidatus Erwinia dacicola: Enterobacteriaceae) in order to develop in unripe olives. Conversely, when feeding on ripe fruit, larval development proceeds independently of these bacteria. Our experiments suggest that bacteria counteract the inhibitory effect of oleuropein—the principal phenolic glycoside in unripe olives. In light of these results, we suggest that the unique symbiosis in olive flies, compared with other frugivorous tephritids, is understood by considering the relationship between the fly, bacteria and fruit chemistry. When applied in an evolutionary context, this approach may also point out the forces which shaped symbioses across the Tephritidae. (author)

  9. Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata

    NARCIS (Netherlands)

    Ifrim, D.C.; Bain, J.M.; Reid, D.M.; Oosting, M.; Verschueren, I.; Gow, N.A.; Krieken, J.H.J.M. van; Brown, G.D.; Kullberg, B.J.; Joosten, L.A.B.; Meer, J.W.M. van der; Koentgen, F.; Erwig, L.P.; Quintin, J.; Netea, M.G.

    2014-01-01

    Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here, we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C.

  10. Reed warbler hosts fine-tune their defenses to track three decades of cuckoo decline.

    Science.gov (United States)

    Thorogood, Rose; Davies, Nicholas B

    2013-12-01

    Interactions between avian hosts and brood parasites can provide a model for how animals adapt to a changing world. Reed warbler (Acrocephalus scirpaceus) hosts employ costly defenses to combat parasitism by common cuckoos (Cuculus canorus). During the past three decades cuckoos have declined markedly across England, reducing parasitism at our study site (Wicken Fen) from 24% of reed warbler nests in 1985 to 1% in 2012. Here we show with experiments that host mobbing and egg rejection defenses have tracked this decline in local parasitism risk: the proportion of reed warbler pairs mobbing adult cuckoos (assessed by responses to cuckoo mounts and models) has declined from 90% to 38%, and the proportion rejecting nonmimetic cuckoo eggs (assessed by responses to model eggs) has declined from 61% to 11%. This is despite no change in response to other nest enemies or mimetic model eggs. Individual variation in both defenses is predicted by parasitism risk during the host's egg-laying period. Furthermore, the response of our study population to temporal variation in parasitism risk can also explain spatial variation in egg rejection behavior in other populations across Europe. We suggest that spatial and temporal variation in parasitism risk has led to the evolution of plasticity in reed warbler defenses. PMID:24299407

  11. Cryptococcus neoformans is resistant to surfactant protein A mediated host defense mechanisms.

    Directory of Open Access Journals (Sweden)

    Steven S Giles

    Full Text Available Initiation of a protective immune response to infection by the pathogenic fungus Cryptococcus neoformans is mediated in part by host factors that promote interactions between immune cells and C. neoformans yeast. Surfactant protein A (SP-A contributes positively to pulmonary host defenses against a variety of bacteria, viruses, and fungi in part by promoting the recognition and phagocytosis of these pathogens by alveolar macrophages. In the present study we investigated the role of SP-A as a mediator of host defense against the pulmonary pathogen, C. neoformans. Previous studies have shown that SP-A binds to acapsular and minimally encapsulated strains of C. neoformans. Using in vitro binding assays we confirmed that SP-A does not directly bind to a fully encapsulated strain of C. neoformans (H99. However, we observed that when C. neoformans was incubated in bronchoalveolar fluid, SP-A binding was detected, suggesting that another alveolar host factor may enable SP-A binding. Indeed, we discovered that SP-A binds encapsulated C. neoformans via a previously unknown IgG dependent mechanism. The consequence of this interaction was the inhibition of IgG-mediated phagocytosis of C. neoformans by alveolar macrophages. Therefore, to assess the contribution of SP-A to the pulmonary host defenses we compared in vivo infections using SP-A null mice (SP-A-/- and wild-type mice in an intranasal infection model. We found that the immune response assessed by cellular counts, TNFalpha cytokine production, and fungal burden in lungs and bronchoalveolar lavage fluids during early stages of infection were equivalent. Furthermore, the survival outcome of C. neoformans infection was equivalent in SP-A-/- and wild-type mice. Our results suggest that unlike a variety of bacteria, viruses, and other fungi, progression of disease with an inhalational challenge of C. neoformans does not appear to be negatively or positively affected by SP-A mediated mechanisms of

  12. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.

    Science.gov (United States)

    Hancock, Robert E W; Sahl, Hans-Georg

    2006-12-01

    Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.

  13. Non-host defense response in a novel Arabidopsis-Xanthomonas citri subsp. citri pathosystem.

    Directory of Open Access Journals (Sweden)

    Chuanfu An

    Full Text Available Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc, is one of the most destructive diseases of citrus. Progress of breeding citrus canker-resistant varieties is modest due to limited resistant germplasm resources and lack of candidate genes for genetic manipulation. The objective of this study is to establish a novel heterologous pathosystem between Xcc and the well-established model plant Arabidopsis thaliana for defense mechanism dissection and resistance gene identification. Our results indicate that Xcc bacteria neither grow nor decline in Arabidopsis, but induce multiple defense responses including callose deposition, reactive oxygen species and salicylic aicd (SA production, and defense gene expression, indicating that Xcc activates non-host resistance in Arabidopsis. Moreover, Xcc-induced defense gene expression is suppressed or attenuated in several well-characterized SA signaling mutants including eds1, pad4, eds5, sid2, and npr1. Interestingly, resistance to Xcc is compromised only in eds1, pad4, and eds5, but not in sid2 and npr1. However, combining sid2 and npr1 in the sid2npr1 double mutant compromises resistance to Xcc, suggesting genetic interactions likely exist between SID2 and NPR1 in the non-host resistance against Xcc in Arabidopsis. These results demonstrate that the SA signaling pathway plays a critical role in regulating non-host defense against Xcc in Arabidopsis and suggest that the SA signaling pathway genes may hold great potential for breeding citrus canker-resistant varieties through modern gene transfer technology.

  14. A Review of Ribonuclease 7's Structure, Regulation, and Contributions to Host Defense.

    Science.gov (United States)

    Becknell, Brian; Spencer, John David

    2016-01-01

    The Ribonuclease A Superfamily is composed of a group of structurally similar peptides that are secreted by immune cells and epithelial tissues. Several members of the Ribonuclease A Superfamily demonstrate antimicrobial activity, and it has been suggested that some of these ribonucleases play an essential role in host defense. Ribonuclease 7 (RNase 7) is an epithelial-derived secreted peptide with potent broad-spectrum antimicrobial activity. This review summarizes the published literature on RNase 7's antimicrobial properties, structure, regulation, and contributions to host defense. In doing so, we conclude by highlighting key knowledge gaps that must be investigated to completely understand the potential of developing RNase 7 as a novel therapeutic for human infectious diseases. PMID:27011175

  15. A Review of Ribonuclease 7’s Structure, Regulation, and Contributions to Host Defense

    Directory of Open Access Journals (Sweden)

    Brian Becknell

    2016-03-01

    Full Text Available The Ribonuclease A Superfamily is composed of a group of structurally similar peptides that are secreted by immune cells and epithelial tissues. Several members of the Ribonuclease A Superfamily demonstrate antimicrobial activity, and it has been suggested that some of these ribonucleases play an essential role in host defense. Ribonuclease 7 (RNase 7 is an epithelial-derived secreted peptide with potent broad-spectrum antimicrobial activity. This review summarizes the published literature on RNase 7’s antimicrobial properties, structure, regulation, and contributions to host defense. In doing so, we conclude by highlighting key knowledge gaps that must be investigated to completely understand the potential of developing RNase 7 as a novel therapeutic for human infectious diseases.

  16. Cuckoos combat socially transmitted defenses of reed warbler hosts with a plumage polymorphism.

    Science.gov (United States)

    Thorogood, Rose; Davies, Nicholas B

    2012-08-01

    In predator-prey and host-parasite interactions, an individual's ability to combat an opponent often improves with experience--for example, by learning to identify enemy signals. Although learning occurs through individual experience, individuals can also assess threats from social information. Such recognition could promote the evolution of polymorphisms if socially transmitted defenses depend on enemy morph frequency. This would allow rare variants to evade detection. Female brood parasitic common cuckoos, Cuculus canorus, are either gray or rufous. The gray morph is a Batesian mimic whose hawk-like appearance deters host attack. Hosts reject this disguise through social learning, increasing their own defenses when they witness neighbors mobbing a cuckoo. Our experiments reveal that social learning is specific to the cuckoo morph that neighbors mob. Therefore, while neighbors alert hosts to local cuckoo activity, frequency-dependent social information selects for a cuckoo plumage polymorphism to thwart host detection. Our results suggest that selection for mimicry and polymorphisms comes not only from personal experience but also from social learning. PMID:22859487

  17. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function

    OpenAIRE

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P.; Kobzik, Lester

    2015-01-01

    Plasma gelsolin (pGSN) functions as part of the “extracellular actin-scavenging system,” but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularens...

  18. Lymphotoxin organizes contributions to host defense and metabolic illness from innate lymphoid cells

    OpenAIRE

    Upadhyay, Vaibhav; Fu, Yang-Xin

    2013-01-01

    The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome....

  19. OXIDATIVE EPITHELIAL HOST DEFENSE IS REGULATED BY INFECTIOUS AND INFLAMMATORY STIMULI

    OpenAIRE

    Gattas, Monica Valencia; Forteza, Radia; Fragoso, Miryam A.; Fregien, Nevis; Salas, Pedro; Salathe, Matthias; Conner, Gregory E.

    2009-01-01

    Epithelia express oxidative anti-microbial protection that uses lactoperoxidase (LPO), hydrogen peroxide (H2O2) and thiocyanate to generate the reactive hypothiocyanite. Duox1 and Duox2, found in epithelia, are hypothesized to provide H2O2 for use by the LPO. To investigate regulation of oxidative LPO-mediated host defense by bacterial and inflammatory stimuli, LPO and Duox mRNA were followed in differentiated primary human airway epithelial cells, challenged with Pseudomonas aeruginosa flage...

  20. Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense

    OpenAIRE

    Cristea, Ileana M.; Diner, Benjamin A.; Budayeva, Hanna G.; Guise, Amanda J.

    2013-01-01

    Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions. Here, we review the mechanisms underlying HDAC regulation during herpesvirus infection. We next discuss the roles of acetylation in host defense against herpesvirus infect...

  1. An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.

    Science.gov (United States)

    Najibi, Mehran; Labed, Sid Ahmed; Visvikis, Orane; Irazoqui, Javier Elbio

    2016-05-24

    The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Gαq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKCα was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution.

  2. Diverse Functions of Pulmonary Collectins in Host Defense of the Lung

    Directory of Open Access Journals (Sweden)

    Shigeru Ariki

    2012-01-01

    Full Text Available Pulmonary surfactant is a mixture of lipids and proteins that covers alveolar surfaces and keeps alveoli from collapsing. Four specific proteins have been identified in surfactant. Among them, two C-type lectins, surfactant proteins A and D (SP-A and SP-D, are known to be implicated in host defense and regulation of inflammatory responses of the lung. These host defense lectins are structurally characterized by N-terminal collagen-like domains and lectin domains and are called pulmonary collectins. They prevent dissemination of infectious microbes by their biological activities including agglutination and growth inhibition. They also promote clearance of microbes by enhancing phagocytosis in macrophages. In addition, they interact with the other pattern-recognition molecules, including Toll-like receptors (TLRs and TLR-associated molecules, CD14 and MD-2, and regulate inflammatory responses. Furthermore, recent studies have demonstrated that these collectins modulate functions of neutrophil-derived innate immune molecules by interacting with them. These findings indicate that pulmonary collectins play critical roles in host defense of the lung.

  3. DMPD: The role of type I interferon production by dendritic cells in host defense. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17544561 The role of type I interferon production by dendritic cells in host defens...tml) (.csml) Show The role of type I interferon production by dendritic cells in host defense. PubmedID 1754...4561 Title The role of type I interferon production by dendritic cells in host de

  4. Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut.

    Science.gov (United States)

    Sana, Thibault G; Flaugnatti, Nicolas; Lugo, Kyler A; Lam, Lilian H; Jacobson, Amanda; Baylot, Virginie; Durand, Eric; Journet, Laure; Cascales, Eric; Monack, Denise M

    2016-08-23

    The mammalian gastrointestinal tract is colonized by a high-density polymicrobial community where bacteria compete for niches and resources. One key competition strategy includes cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), a multiprotein needle-like apparatus that injects effector proteins into prokaryotic and/or eukaryotic target cells. However, the contribution of T6SS antibacterial activity during pathogen invasion of the gut has not been demonstrated. We report that successful establishment in the gut by the enteropathogenic bacterium Salmonella enterica serovar Typhimurium requires a T6SS encoded within Salmonella pathogenicity island-6 (SPI-6). In an in vitro setting, we demonstrate that bile salts increase SPI-6 antibacterial activity and that S Typhimurium kills commensal bacteria in a T6SS-dependent manner. Furthermore, we provide evidence that one of the two T6SS nanotube subunits, Hcp1, is required for killing Klebsiella oxytoca in vitro and that this activity is mediated by the specific interaction of Hcp1 with the antibacterial amidase Tae4. Finally, we show that K. oxytoca is killed in the host gut in an Hcp1-dependent manner and that the T6SS antibacterial activity is essential for Salmonella to establish infection within the host gut. Our findings provide an example of pathogen T6SS-dependent killing of commensal bacteria as a mechanism to successfully colonize the host gut. PMID:27503894

  5. DMPD: Toll-like receptors and the host defense against microbial pathogens: bringingspecificity to the innate-immune system. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15075354 Toll-like receptors and the host defense against microbial pathogens: brin... the host defense against microbial pathogens: bringingspecificity to the innate-...immune system. PubmedID 15075354 Title Toll-like receptors and the host defense against microbial pathogens:

  6. Guardian of the Human Genome: Host Defense Mechanisms against LINE-1 Retrotransposition

    Science.gov (United States)

    Ariumi, Yasuo

    2016-01-01

    Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome, encoding a newly identified ORF0 with unknown function, ORF1p with RNA-binding activity and ORF2p with endonuclease and reverse transcriptase activities required for L1 retrotransposition. L1 utilizes an endonuclease (EN) to insert L1 cDNA into target DNA, which induces DNA double-strand breaks (DSBs). The ataxia-telangiectasia mutated (ATM) is activated by DSBs and subsequently the ATM-signaling pathway plays a role in regulating L1 retrotransposition. In addition, the host DNA repair machinery such as non-homologous end-joining (NHEJ) repair pathway is also involved in L1 retrotransposition. On the other hand, L1 is an insertional mutagenic agent, which contributes to genetic change, genomic instability, and tumorigenesis. Indeed, high-throughput sequencing-based approaches identified numerous tumor-specific somatic L1 insertions in variety of cancers, such as colon cancer, breast cancer, and hepatocellular carcinoma (HCC). In fact, L1 retrotransposition seems to be a potential factor to reduce the tumor suppressive property in HCC. Furthermore, recent study demonstrated that a specific viral-human chimeric transcript, HBx-L1, contributes to hepatitis B virus (HBV)-associated HCC. In contrast, host cells have evolved several defense mechanisms protecting cells against retrotransposition including epigenetic regulation through DNA methylation and host defense factors, such as APOBEC3, MOV10, and SAMHD1, which restrict L1 mobility as a guardian of the human genome. In this review, I focus on somatic L1 insertions into the human genome in cancers and host defense mechanisms against deleterious L1 insertions. PMID:27446907

  7. The adaptor molecule Trif contributes to murine host defense during Leptospiral infection.

    Science.gov (United States)

    Jayaraman, Priya A; Devlin, Amy A; Miller, Jennifer C; Scholle, Frank

    2016-09-01

    Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon β (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans. PMID:27259371

  8. Antibacterial activity of the sponge Suberites domuncula and its primmorphs: Potential basis for epibacterial chemical defense

    Digital Repository Service at National Institute of Oceanography (India)

    Thakur, N.L.; Hentschel, U.; Krasko, A.; Pabel, C.T.; Anil, A.C.; Mueller, W.E.G.

    perforin and displayed antibacterial activity. Human perforin is found in lytic granules of cytotoxic natural killer and T-cells (Lowin et al. 1994). After release, perforin forms pores in the target cell membranes, initiating osmotic lysis. Hence, perforin... in membrane-bound proteins and in secreted molecules (Campbell & Bork 1993). Furthermore, a C2 domain, with lower similarity, between aa 72 to aa 155 is present; the C2 domain is thought to be involved in Ca 2+ -dependent phospho- lipid binding (Davletov...

  9. Viral RNA Silencing Suppressors (RSS): Novel Strategy of Viruses to Ablate the Host RNA Interference (RNAi) Defense System

    OpenAIRE

    Bivalkar-Mehla, Shalmali; Vakharia, Janaki; Mehla, Rajeev; Abreha, Measho; Kanwar, Jagat Rakesh; Tikoo, Akshay; Chauhan, Ashok

    2010-01-01

    Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recen...

  10. The role of NOD1 and NOD2 in host defense against chlamydial infection.

    Science.gov (United States)

    Zou, Yan; Lei, Wenbo; He, Zhansheng; Li, Zhongyu

    2016-09-01

    Chlamydial species are common intracellular parasites that cause various diseases, mainly characterized by persistent infection, which lead to inflammatory responses modulated by pattern recognition receptors (PRRs). The best understood PRRs are the extracellular Toll-like receptors, but recent significant advances have focused on two important proteins, NOD1 and NOD2, which are members of the intracellular nucleotide-binding oligomerization domain receptor family and are capable of triggering the host innate immune signaling pathways. This results in the production of pro-inflammatory cytokines, which is vital for an adequate host defense against intracellular chlamydial infection. NOD1/2 ligands are known to derive from peptidoglycan, and the latest research has resolved the paradox of whether chlamydial species possess this bacterial cell wall component; this finding is likely to promote in-depth investigations into the interaction between the NOD proteins and chlamydial pathogens. In this review, we summarize the basic characteristics and signal transduction functions of NOD1 and NOD2 and highlight the new research on the roles of NOD1 and NOD2 in the host defense against chlamydial infection.

  11. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.

    Directory of Open Access Journals (Sweden)

    T Eoin West

    2014-09-01

    Full Text Available Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encoding type III secretion systems, B. pseudomallei may trigger numerous host pathogen recognition receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4, along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome in the cytoplasm that responds to flagellin (in mice and type III secretion system components (in mice and humans. In a murine model of respiratory melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in the lung much of this effect was attributable to Nlrc4, despite relative preservation of pulmonary IL-1β production in Nlrc4(-/- mice. Histologically, deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated with survival in melioidosis patients with pulmonary involvement. Co-inheritance of rs6757121 and a functional TLR5 polymorphism had an additive effect on survival. Our results show that NLRC4 and TLR5, key components of two flagellin sensing pathways, each contribute to host defense in respiratory melioidosis.

  12. Strong down-regulation of glycophorin genes: A host defense mechanism against rotavirus infection.

    Science.gov (United States)

    Salas, Antonio; Marco-Puche, Guillermo; Triviño, Juan Carlos; Gómez-Carballa, Alberto; Cebey-López, Miriam; Rivero-Calle, Irene; Vilanova-Trillo, Lucía; Rodríguez-Tenreiro, Carmen; Gómez-Rial, José; Martinón-Torres, Federico

    2016-10-01

    The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection. Most interesting was the inhibition of genes of the glycophorins A and B (GYPA/B) family, which are the major sialoglycoproteins of the human erythrocyte membrane and receptor of several viruses for host invasion. RV infection induces a complex and global response in the host. The strong inhibition of glycophorins suggests a novel defense mechanism of the host to prevent viral infection, inhibiting the expression of receptors used by the virus for infection. The present results add further support to the systemic nature of RV infection. PMID:27491455

  13. Exploring the pharmacological potential of promiscuous host-defense peptides: from natural screenings to biotechnological applications

    Directory of Open Access Journals (Sweden)

    Osmar Nascimento Silva

    2011-11-01

    Full Text Available In the last few years, the number of bacteria with enhanced resistance to conventional antibiotics has dramatically increased. Most of such bacteria belong to regular microbial flora, becoming a real challenge, especially for immune-depressed patients. Since the treatment is sometimes extremely expensive, and in some circumstances completely inefficient for the most severe cases, researchers are still determined to discover novel compounds. Among them, host-defense peptides (HDPs have been found as the first natural barrier against microorganisms in nearly all living groups. This molecular class has been gaining attention every day for multiple reasons. For decades, it was believed that these defense peptides had been involved only with the permeation of the lipid bilayer in pathogen membranes, their main target. Currently, it is known that these peptides can bind to numerous targets, as well as lipids including proteins and carbohydrates, from the surface to deep within the cell. Moreover, by using in vivo models, it was shown that host-defense peptides could act both in pathogens and cognate hosts, improving immunological functions as well as acting through multiple pathways to control infections. This review focuses on structural and functional properties of HDP peptides and the additional strategies used to select them. Furthermore, strategies to avoid problems in large scale manufacture by using molecular and biochemical techniques will also be explored. In summary, this review intends to construct a bridge between academic research and pharmaceutical industry, providing novel insights into the utilization of HDPs against resistant bacterial strains that cause infections in humans.

  14. MyD88 Signaling Regulates Both Host Defense and Immunopathogenesis during Pneumocystis Infection

    OpenAIRE

    Bello-Irizarry, Sheila N.; Wang, Jing; Johnston, Carl J.; Gigliotti, Francis; Wright, Terry W.

    2013-01-01

    The immune response protects against Pneumocystis infection, but is also a key component of PcP-related immunopathogenesis. Signaling through MyD88 is critical for activation of immune pathways downstream of TLRs and IL-1 receptor. To determine whether MyD88 regulates normal host defense against Pneumocystis, non-immunosuppressed wild-type (WT) and MyD88 deficient mice were infected. MyD88−/− mice had higher early Pneumocystis burdens than WT mice, but mounted an effective adaptive immune res...

  15. Host defense peptides as effector molecules of the innate immune response: a sledgehammer for drug resistance?

    Science.gov (United States)

    Steinstraesser, Lars; Kraneburg, Ursula M; Hirsch, Tobias; Kesting, Marco; Steinau, Hans-Ulrich; Jacobsen, Frank; Al-Benna, Sammy

    2009-09-09

    Host defense peptides can modulate the innate immune response and boost infection-resolving immunity, while dampening potentially harmful pro-inflammatory (septic) responses. Both antimicrobial and/or immunomodulatory activities are an integral part of the process of innate immunity, which itself has many of the hallmarks of successful anti-infective therapies, namely rapid action and broad-spectrum antimicrobial activities. This gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections. This review details the role and activities of these peptides, and examines their applicability as development candidates for use against bacterial infections.

  16. The late endosomal adaptor p14 is a macrophage host-defense factor against Salmonella infection.

    Science.gov (United States)

    Taub, Nicole; Nairz, Manfred; Hilber, Diana; Hess, Michael W; Weiss, Günter; Huber, Lukas A

    2012-06-01

    The outcome of an infection depends on the balance between host resistance and bacterial virulence. Here, we show that the late endosomal adaptor p14 (also known as LAMTOR2) is one of the components for cellular host defense against the intracellular pathogen Salmonella enterica serovar Typhimurium. During Salmonella infection, the complex of p14 and MP1 is required for the accurately timed transport of Salmonella through the endolysosomal system. Loss of p14 opens a time window that allows Salmonella to populate a replication niche, in which early and late antimicrobial effector systems, comprising NADPH phagocytic oxidase and inducible nitric oxide synthase, respectively, are inappropriately activated. Thus, p14 supports the accurate transport of Salmonella through the endolysosomal system, thereby limiting bacterial replication in both, professional phagocytes and in non-phagocytic cells in vitro, and helps mice to successfully battle Salmonella infection in vivo.

  17. mRNA expression profiling reveals a role of Helicobacter pylorivacuolating toxin in escaping host defense

    Institute of Scientific and Technical Information of China (English)

    Jian-Ping Yuan; Tao Li; Zhen-Hong Li; Gui-Zhen Yang; Bao-Yu Hu; Xiao-Dong Shi; Tie-Liu Shi; Shan-Qing Tong; Xiao-Kui Guo

    2004-01-01

    AIM: To study the immune response of host to Helicobacter pylori VacA.METHODS: The monocyte/macrophage-like U937 cells were infected with Helicobacter pylori vacA-positive strain NCTC 11638 or isogenic vacA-negative mutant. Differentially expressed genes were identified at 2, 6, 10, and 24 h postinfection by cDNA microarray. Differential expressions of some genes were confirmed by Northern blot.RESULTS: More than 100 genes altered their mRNA expression at different time points respectively, many of which were identified to be related to immune evasion.CONCLUSION: VacA is a crucial element for H pylorito escape from host immune defense by means of differentially regulating the expression of some related genes. These genes, previously known or unknown to be involved in the mechanism of immune evasion, deserve further investigation to unearth much more information complicated in the immune response.

  18. The Cnes2 locus on mouse chromosome 17 regulates host defense against cryptococcal infection through pleiotropic effects on host immunity.

    Science.gov (United States)

    Shourian, Mitra; Flaczyk, Adam; Angers, Isabelle; Mindt, Barbara C; Fritz, Jörg H; Qureshi, Salman T

    2015-12-01

    The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. neoformans susceptibility (Cnes1, Cnes2, and Cnes3). To validate and characterize the role of Cnes2 during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2 mice 35 days after C. neoformans infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-γ) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b(+) dendritic cells, and CD4(+) cells in B6.CBA-Cnes2 than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2 mice. Taken together, these findings demonstrate that the Cnes2 interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization following C. neoformans infection.

  19. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function.

    Science.gov (United States)

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P; Kobzik, Lester

    2015-07-01

    Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging system," but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-) mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ∼15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia. PMID:25957291

  20. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function

    Science.gov (United States)

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P.

    2015-01-01

    Plasma gelsolin (pGSN) functions as part of the “extracellular actin-scavenging system,” but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser1177) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3−/− macrophages in vitro or bacterial clearance in NOS3−/− mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ∼15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia. PMID:25957291

  1. The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis.

    Science.gov (United States)

    Ifrim, Daniela C; Quintin, Jessica; Courjol, Flavie; Verschueren, Ineke; van Krieken, J Han; Koentgen, Frank; Fradin, Chantal; Gow, Neil A R; Joosten, Leo A B; van der Meer, Jos W M; van de Veerdonk, Frank; Netea, Mihai G

    2016-04-01

    Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies. PMID:27046240

  2. Exploration of Phage-Host Interactions in Fish Pathogen Vibrio anguillarum and Anti-Phage Defense Strategies

    DEFF Research Database (Denmark)

    Tan, Demeng

    of bacterial pathogenicity development. Therefore, successful application of phage therapy in the treatment of vibriosis requires a detailed understanding of phage-host interactions, especially with regards to anti-phage defense mechanisms in the host. Part I. As a first approach, 24 V. anguillarum and 13....... In conclusion, this thesis provides a first insight into the dynamic vibriophage-host interactions, indicating the complexity of phage therapy in the treatment of vibriosis, regarding the evolution of anti-phage defense mechanisms, gene regulation, quorum sensing, biofilm formation, as well as pathogenesis...... outcome of phage therapy and QS inhibiting molecules....

  3. Host Active Defense Responses Occur within 24 Hours after Pathogen Inoculation in the Rice Blast System

    Institute of Scientific and Technical Information of China (English)

    WANG Zhong-hua; JIA Yu-lin; LIN Hui; Adair INTERN; Barbara VALENT; J. Neil RUTGER

    2007-01-01

    Phenotypical, cytological and molecular responses of rice to the fungus Magnaporthe grisea were studied using rice cultivars and lesion mimic plants. The cultivar Katy was susceptible to several virulent M. grisea isolates, and a Sekiguchi like-lesion mimic mutant of Katy (LmmKaty) showed enhanced resistance to these isolates. Lesion mimic phenotype of LmmKaty was rapidly induced by virulent M. grisea isolates or by avirulent ones only at high levels of inoculum.Autofluorescence (a sign of an active defense response) was visible under ultraviolet light 24 h after localized inoculation in the incompatible interaction, whereas, not evident in the compatible interaction. Autofluorescence was also observed in LmmKaty 20 h after pathogen inoculation, indicating that rapid cell death is a mechanism of LmmKaty to restrict pathogen invasion. Rapid accumulations of defense related (DR) gene transcripts, phenylalanine ammonia lyase and β-glucanase,were observed beginning at 6 h and were obvious at 16 h and 24 h after inoculation in an incompatible interaction. Rapid transcript accumulations of PR-1 and chitinase had occurred by 24 h after inoculation in an incompatible interaction.Accumulations of these transcripts were delayed in the compatible interaction. These results indicate that host active defense responses occur 24 h after pathogen inoculation and that LmmKaty exhibits enhanced resistance to M. grisea. It is suggested that the autofluorescence and expression of the DR genes after heavy inoculation are important cytological and molecular markers respectively for early determination of the host response to M. grisea in the rice blast system.

  4. Adult Drosophila melanogaster evolved for antibacterial defense invest in infection-induced expression of both humoral and cellular immunity genes

    Directory of Open Access Journals (Sweden)

    McGraw Elizabeth A

    2011-08-01

    Full Text Available Abstract Background While the transcription of innate immunity genes in response to bacterial infection has been well-characterised in the Drosophila model, we recently demonstrated the capacity for such transcription to evolve in flies selected for improved antibacterial defense. Here we use this experimental system to examine how insects invest in constitutive versus infection-induced transcription of immunity genes. These two strategies carry with them different consequences with respect to energetic and pleiotropic costs and may be more or less effective in improving defense depending on whether the genes contribute to humoral or cellular aspects of immunity. Findings Contrary to expectation we show that selection preferentially increased the infection-induced expression of both cellular and humoral immunity genes. Given their functional roles, infection induced increases in expression were expected for the humoral genes, while increases in constitutive expression were expected for the cellular genes. We also report a restricted ability to improve transcription of immunity genes that is on the order of 2-3 fold regardless of total transcription level of the gene. Conclusions The evolved increases in infection-induced expression of the cellular genes may result from specific cross talk with humoral pathways or from generalised strategies for enhancing immunity gene transcription. A failure to see improvements in constitutive expression of the cellular genes suggests either that increases might come at too great a cost or that patterns of expression in adults are decoupled from the larval phase where increases would be most effective. The similarity in fold change increase across all immunity genes may suggest a shared mechanism for the evolution of increased transcription in small, discrete units such as duplication of cis-regulatory elements.

  5. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

    Full Text Available Rats with Metabolic Syndrome (MetaS have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S. aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS and high capacity runner (HCR rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF, and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  6. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Science.gov (United States)

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  7. Circulating lipoproteins are a crucial component of host defense against invasive Salmonella typhimurium infection.

    Directory of Open Access Journals (Sweden)

    Mihai G Netea

    Full Text Available BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS, thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/- mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p<0.001, and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an altered biodistribution of the microorganisms during the first hours of infection: after intravenous injection of Salmonella into LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the circulation from where they were efficiently cleared, with decreased organ invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism against invasive Salmonella infection, by blocking adhesion of Salmonella to the host cells and subsequent tissue invasion.

  8. Inbreeding compromises host plant defense gene expression and improves herbivore survival.

    Science.gov (United States)

    Portman, Scott L; Kariyat, Rupesh R; Johnston, Michelle A; Stephenson, Andrew G; Marden, James H

    2015-01-01

    Inbreeding commonly occurs in flowering plants and often results in a decline in the plant's defense response. Insects prefer to feed and oviposit on inbred plants more than outbred plants--suggesting that selecting inbred host plants offers them fitness benefits. Until recently, no studies have examined the effects of host plant inbreeding on insect fitness traits such as growth and dispersal ability. In a recent article, we documented that tobacco hornworm (Manduca sexta L.) larvae that fed on inbred horsenettle (Solanum carolinense L.) plants exhibited accelerated larval growth and increased adult flight capacity compared to larvae that fed on outbred plants. Here we report that M. sexta mortality decreased by 38.2% when larvae were reared on inbred horsenettle plants compared to larvae reared on outbreds. Additionally, inbred plants showed a notable reduction in the average relative expression levels of lipoxygenease-D (LoxD) and 12-oxophytodienoate reductase-3 (OPR3), two genes in the jasmonic acid signaling pathway that are upregulated in response to herbivore damage. Our study presents evidence that furthers our understanding of the biochemical mechanism responsible for differences in insect performance on inbred vs. outbred host plants. PMID:26039489

  9. Biomembrane interactions reveal the mechanism of action of surface-immobilized host defense IDR-1010 peptide.

    Science.gov (United States)

    Gao, Guangzheng; Cheng, John T J; Kindrachuk, Jason; Hancock, Robert E W; Straus, Suzana K; Kizhakkedathu, Jayachandran N

    2012-02-24

    Dissecting the mechanism of action of surface-tethered antimicrobial and immunomodulatory peptides is critical to the design of optimized anti-infection coatings on biomedical devices. To address this, we compared the biomembrane interactions of host defense peptide IDR-1010cys (1) in free form, (2) as a soluble polymer conjugate, and (3) with one end tethered to a solid support with model bacterial and mammalian lipid membranes. Our results show that IDR-1010cys in all three distinct forms interacted with bacterial and mammalian lipid vesicles, but the extent of the interactions as monitored by the induction of secondary structure varied. The enhanced interaction of surface-tethered peptides is well correlated with their very good antimicrobial activities. Our results demonstrate that there may be a difference in the mechanism of action of surface-tethered versus free IDR-1010cys.

  10. Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts.

    Science.gov (United States)

    Grassmé, H; Jendrossek, V; Riehle, A; von Kürthy, G; Berger, J; Schwarz, H; Weller, M; Kolesnick, R; Gulbins, E

    2003-03-01

    Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen. PMID:12563314

  11. Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides

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    Hao Li

    2016-06-01

    Full Text Available Host defense peptides (HDPs are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs.

  12. Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity.

    Science.gov (United States)

    Auvynet, Constance; Rosenstein, Yvonne

    2009-11-01

    The term 'antimicrobial peptides' refers to a large number of peptides first characterized on the basis of their antibiotic and antifungal activities. In addition to their role as endogenous antibiotics, antimicrobial peptides, also called host defense peptides, participate in multiple aspects of immunity (inflammation, wound repair, and regulation of the adaptive immune system) as well as in maintaining homeostasis. The possibility of utilizing these multifunctional molecules to effectively combat the ever-growing group of antibiotic-resistant pathogens has intensified research aimed at improving their antibiotic activity and therapeutic potential, without the burden of an exacerbated inflammatory response, but conserving their immunomodulatory potential. In this minireview, we focus on the contribution of small cationic antimicrobial peptides - particularly human cathelicidins and defensins - to the immune response and disease, highlighting recent advances in our understanding of the roles of these multifunctional molecules.

  13. Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity.

    Science.gov (United States)

    Takahashi, Daisuke; Shukla, Sanjeev K; Prakash, Om; Zhang, Guolong

    2010-09-01

    Antimicrobial host defense peptides (HDPs) are a critical component of the innate immunity with microbicidal, endotoxin-neutralizing, and immunostimulatory properties. HDPs kill bacteria primarily through non-specific membrane lysis, therefore with a less likelihood of provoking resistance. Extensive structure-activity relationship studies with a number of HDPs have revealed that net charge, amphipathicity, hydrophobicity, and structural propensity are among the most important physicochemical and structural parameters that dictate their ability to interact with and disrupt membranes. A delicate balance among these factors, rather than a mere alteration of a single factor, is critically important for HDPs to ensure the antimicrobial potency and target cell selectivity. With a better understanding of the structural determinants of HDPs for their membrane-lytic activities, it is expected that novel HDP-based antimicrobials with minimum toxicity to eukaryotic cells can be developed for resistant infections, which have become a global public health crisis.

  14. Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver.

    Science.gov (United States)

    McVicker, Benita L; Thiele, Geoffrey M; Tuma, Dean J; Casey, Carol A

    2014-09-01

    The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.

  15. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.

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    Constantin F Urban

    2009-10-01

    Full Text Available Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins and the release of Neutrophil Extracellular Traps (NETs. NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.

  16. Sequestration of host plant glucosinolates in the defensive hemolymph of the sawfly Athalia rosae.

    Science.gov (United States)

    Müller, C; Agerbirk, N; Olsen, C E; Boevé, J L; Schaffner, U; Brakefield, P M

    2001-12-01

    Interactions between insects and glucosinolate-containing plant species have been investigated for a long time. Although the glucosinolate-myrosinase system is believed to act as a defense mechanism against generalist herbivores and fungi, several specialist insects use these secondary metabolites for host plant finding and acceptance and can handle them physiologically. However, sequestration of glucosinolates in specialist herbivores has been less well studied. Larvae of the tumip sawfly Athalia rosae feed on several glucosinolate-containing plant species. When larvae are disturbed by antagonists, they release one or more small droplets of hemolymph from their integument. This "reflex bleeding" is used as a defense mechanism. Specific glucosinolate analysis, by conversion to desulfoglucosinolates and analysis of these by high-performance liquid chromatography coupled to diode array UV spectroscopy and mass spectrometry, revealed that larvae incorporate and concentrate the plant's characteristic glucosinolates from their hosts. Extracts of larvae that were reared on Sinapis alba contained sinalbin, even when the larvae were first starved for 22 hr and, thus, had empty guts. Hemolymph was analyzed from larvae that were reared on either S. alba, Brassica nigra, or Barbarea stricta. Leaves were analyzed from the same plants the larvae had fed on. Sinalbin (from S. alba), sinigrin (B. nigra), or glucobarbarin and glucobrassicin (B. stricta) were present in leaves in concentrations less than 1 micromol/g fresh weight, while the same glucosinolates could be detected in the larvae's hemolymph in concentrations between 10 and 31 micromol/g fresh weight, except that glucobrassicin was present only as a trace. In larval feces, only trace amounts of glucosinolates (sinalbin and sinigrin) could be detected. The glucosinolates were likewise found in freshly emerged adults, showing that the sequestered phytochemicals were transferred through the pupal stage. PMID:11789955

  17. Modulation of antimicrobial host defense peptide gene expression by free fatty acids.

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    Lakshmi T Sunkara

    Full Text Available Routine use of antibiotics at subtherapeutic levels in animal feed drives the emergence of antimicrobial resistance. Development of antibiotic-alternative approaches to disease control and prevention for food animals is imperatively needed. Previously, we showed that butyrate, a major species of short-chain fatty acids (SCFAs fermented from undigested fiber by intestinal microflora, is a potent inducer of endogenous antimicrobial host defense peptide (HDP genes in the chicken (PLoS One 2011, 6: e27225. In the present study, we further revealed that, in chicken HD11 macrophages and primary monocytes, induction of HDPs is largely in an inverse correlation with the aliphatic hydrocarbon chain length of free fatty acids, with SCFAs being the most potent, medium-chain fatty acids moderate and long-chain fatty acids marginal. Additionally, three SCFAs, namely acetate, propionate, and butyrate, exerted a strong synergy in augmenting HDP gene expression in chicken cells. Consistently, supplementation of chickens with a combination of three SCFAs in water resulted in a further reduction of Salmonella enteritidis in the cecum as compared to feeding of individual SCFAs. More importantly, free fatty acids enhanced HDP gene expression without triggering proinflammatory interleukin-1β production. Taken together, oral supplementation of SCFAs is capable of boosting host immunity and disease resistance, with potential for infectious disease control and prevention in animal agriculture without relying on antibiotics.

  18. Splenic autotransplantation in rabbits: no restoration of response to host defense

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective:TO explore the effectiveness of splenic tissue autotransplantation in restoring host defense. Methods: Rabbits were divided into three groups,Sham Operation(SO), Splenic Autotransplantation(SA)and Total Splenectomy(TS), and dynamic changes in histology and immunology were observed for over 24 weeks. Results: Histologic study shows that the white pulps were poorly developed and central arterioles disappeared in the regenerated splenic tissue. The weight of regenerated spleens recovered six months later in SA was 11% of that in SO, and was significantly reduced comparing with the implanted weight( P <0.05). Tere were no significant difference in the number of T lymphocytes and the levels of serum lysozyme among the three groups. A poor antibody response by the rabbits of SA and TS as compared to those of SO was noted after the primary intravenous administration with sheep red blood cells. After the challenge with type 3 pneumococci intravenously, pneumococcal clearance from bloodstream in SA did not differ significantly from that in TS,but was marKedly delayed compared with that in SO(P<0.01). Conclusion: The results indicate that the low quantity and poor quality of the regenerated spleens may contribute to the inferior immunoprotective ability of 1/3 splenic autotransplantation. Therefore, it implies that the regenerated spleens can not fully compensate the original one in im-munology, especially, host resistance to infection.

  19. Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection.

    Science.gov (United States)

    Gladiator, André; Wangler, Nicolette; Trautwein-Weidner, Kerstin; LeibundGut-Landmann, Salomé

    2013-01-15

    IL-17-mediated immunity has emerged as a crucial host defense mechanism against fungal infections. Although Th cells are generally thought to act as the major source of IL-17 in response to Candida albicans, we show that fungal control is mediated by IL-17-secreting innate lymphoid cells (ILCs) and not by Th17 cells. By using a mouse model of oropharyngeal candidiasis we found that IL-17A and IL-17F, which are both crucial for pathogen clearance, are produced promptly upon infection in an IL-23-dependent manner, and that ILCs in the oral mucosa are the main source for these cytokines. Ab-mediated depletion of ILCs in RAG1-deficient mice or ILC deficiency in retinoic acid-related orphan receptor c(-/-) mice resulted in a complete failure to control the infection. Taken together, our data uncover the cellular basis for the IL-23/IL-17 axis, which acts right at the onset of infection when it is most needed for fungal control and host protection.

  20. SP-A and SP-D in host defense against fungal infections and allergies.

    Science.gov (United States)

    Pandit, Hrishikesh; Madhukaran, Shanmuga P; Nayak, Annapurna; Madan, Taruna

    2012-01-01

    Innate immunity mediated by pattern recognition proteins is relevant in the host defense against fungi. SP-A and SP-D are two such proteins belonging to the class of collagen domain containing C-type lectins, or collectins. They bind to the sugar moieties present on the cell walls of various fungi in a dose dependent manner via their carbohydrate recognition domain (CRD). SP-A and SP-D directly interact with alveolar macrophages, neutrophils, lymphocytes. We review these roles of SP-A and SP-D against various clinically relevant fungal pathogens and fungal allergens. SP-A and SP-D gene deficient mice showed increased susceptibility/ resistance to various fungal infections. Patients of fungal infections and allergies are reported with alterations in the serum or lung lavage levels of SP-A and SP-D. There are studies associating the gene polymorphisms in SP-A and SP-D with alterations in their levels or functions or susceptibility of the host to fungal diseases. In view of the protective role of SP-D in murine models of Aspergillus fumigatus infections and allergies, therapeutic use of SP-D could be explored further.

  1. Flagellum-Mediated Biofilm Defense Mechanisms of Pseudomonas aeruginosa against Host-Derived Lactoferrin ▿

    Science.gov (United States)

    Leid, Jeff G.; Kerr, Mathias; Selgado, Candice; Johnson, Chelsa; Moreno, Gabriel; Smith, Alyssa; Shirtliff, Mark E.; O'Toole, George A.; Cope, Emily K.

    2009-01-01

    Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant lacks flagella, which results in defects in early biofilm development (up to 36 h). For these experiments, the flgK-disrupted strain and the parental strain (PA14) were used in a modified version of the 96-well plate microtiter assay. Biofilms were challenged with freshly isolated human leukocytes for 4 to 6 h and viable bacteria enumerated by CFU. Subsequent to the challenge, both mononuclear cells (monocytes and lymphocytes) and neutrophils, along with tumor necrosis factor alpha (TNF-α), were required for optimal killing of the flgK biofilm bacteria. We identified a cytokine cross talk network between mononuclear cells and neutrophils that was essential to the production of lactoferrin and bacterial killing. Our data suggest that TNF-α is secreted from mononuclear cells, causing neutrophil activation, resulting in the secretion of bactericidal concentrations of lactoferrin. These results extend previous studies of the importance of lactoferrin in the innate immune defense against bacterial biofilms. PMID:19651866

  2. Post-ejection nest-desertion of common cuckoo hosts : a second defense mechanism or avoiding reduced reproductive success?

    NARCIS (Netherlands)

    Moskat, Csaba; Rosendaal, Erik C.; Boers, Myra; Zoelei, Aniko; Ban, Miklos; Komdeur, Jan; Soler, M.

    2011-01-01

    Hosts of the common cuckoo (Cuculus canorus), an avian brood parasite, develop antiparasite defense mechanisms to increase their reproductive success. Ejection of the parasite egg and desertion of the parasitized nest are the most typical adaptations in response to brood parasitism, but nest deserti

  3. Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

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    David Proud

    Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

  4. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    Science.gov (United States)

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. PMID:26927796

  5. Identification of genetic loci required for Campylobacter resistance to fowlicidin-1, a chicken host defense peptide

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    Ky Van Hoang

    2012-03-01

    Full Text Available Antimicrobial peptides (AMPs are critical components of host defense limiting bacterial infections at the gastrointestinal mucosal surface. Bacterial pathogens have co-evolved with host innate immunity and developed means to counteract the effect of endogenous AMPs. However, molecular mechanisms of AMP resistance in Campylobacter, an important human food borne pathogen with poultry as a major reservoir, are still largely unknown. In this study, random transposon mutagenesis and targeted site-directed mutagenesis approaches were used to identify genetic loci contributing Campylobacter resistance to fowlicidin-1, a chicken AMP belonging to cathelicidin family. An efficient transposon mutagenesis approach (EZ::TNTM Transposome in conjunction with a microtiter plate screening identified three mutants whose susceptibilities to fowlicidin-1 were significantly increased. Backcrossing of the transposon mutations into parent strain confirmed that the AMP-sensitive phenotype in each mutant was linked to the specific transposon insertion. Direct sequencing showed that these mutants have transposon inserted in the genes encoding two-component regulator CbrR, transporter CjaB, and putative trigger factor Tig. Genomic analysis also revealed an operon (Cj1580c-1584c that is homologous to sapABCDF, an operon conferring resistance to AMP in other pathogens. Insertional inactivation of Cj1583c (sapB significantly increased susceptibility of Campylobacter to fowlicidin-1. The sapB as well as tig and cjaB mutants were significantly impaired in their ability to compete with their wild-type strain 81-176 to colonize the chicken cecum. Together, this study identified four genetic loci in Campylobacter that will be useful for characterizing molecular basis of Campylobacter resistance to AMPs, a significant knowledge gap in Campylobacter pathogenesis.

  6. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.

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    Shikha Bhatia

    Full Text Available The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1, a key marker of alternatively activated macrophages (AAMs. The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c(+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.

  7. The DNA Sensor AIM2 Maintains Intestinal Homeostasis via Regulation of Epithelial Antimicrobial Host Defense.

    Science.gov (United States)

    Hu, Shuiqing; Peng, Lan; Kwak, Youn-Tae; Tekippe, Erin McElvania; Pasare, Chandrashekhar; Malter, James S; Hooper, Lora V; Zaki, Md Hasan

    2015-12-01

    Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2(-/-) mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2(-/-) mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2(-/-) mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2(-/-) mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.

  8. The DNA Sensor AIM2 Maintains Intestinal Homeostasis via Regulation of Epithelial Antimicrobial Host Defense

    Directory of Open Access Journals (Sweden)

    Shuiqing Hu

    2015-12-01

    Full Text Available Microbial pattern molecules in the intestine play immunoregulatory roles via diverse pattern recognition receptors. However, the role of the cytosolic DNA sensor AIM2 in the maintenance of intestinal homeostasis is unknown. Here, we show that Aim2−/− mice are highly susceptible to dextran sodium sulfate-induced colitis that is associated with microbial dysbiosis as represented by higher colonic burden of commensal Escherichia coli. Colonization of germ-free mice with Aim2−/− mouse microbiota leads to higher colitis susceptibility. In-depth investigation of AIM2-mediated host defense responses reveals that caspase-1 activation and IL-1β and IL-18 production are compromised in Aim2−/− mouse colons, consistent with defective inflammasome function. Moreover, IL-18 infusion reduces E. coli burden as well as colitis susceptibility in Aim2−/− mice. Altered microbiota in inflammasome-defective mice correlate with reduced expression of several antimicrobial peptides in intestinal epithelial cells. Together, these findings implicate DNA sensing by AIM2 as a regulatory mechanism for maintaining intestinal homeostasis.

  9. Assessment of antimicrobial (host defense) peptides as anti-cancer agents.

    Science.gov (United States)

    Douglas, Susan; Hoskin, David W; Hilchie, Ashley L

    2014-01-01

    Cationic antimicrobial (host defense) peptides (CAPs) are able to kill microorganisms and cancer cells, leading to their consideration as novel candidate therapeutic agents in human medicine. CAPs can physically associate with anionic membrane structures, such as those found on cancer cells, causing pore formation, intracellular disturbances, and leakage of cell contents. In contrast, normal cells are less negatively-charged and are typically not susceptible to CAP-mediated cell death. Because the interaction of CAPs with cells is based on charge properties rather than cell proliferation, both rapidly dividing and quiescent cancer cells, as well as multidrug-resistant cancer cells, are targeted by CAPs, making CAPS potentially valuable as anti-cancer agents. CAPs often exist as families of peptides with slightly different amino acid sequences. In addition, libraries of synthetic peptide variants based on naturally occurring CAP templates can be generated in order to improve upon their action. High-throughput screens are needed to quickly and efficiently assess the suitability of each CAP variant. Here we present the methods for assessing CAP-mediated cytotoxicity against cancer cells (suspension and adherent) and untransformed cells (measured using the tritiated thymidine-release or MTT assay), and for discriminating between cell death caused by necrosis (measured using lactate dehydrogenase- or (51)Cr-release assays), or apoptosis and necrosis (single-stranded DNA content measured by flow cytometry). In addition the clonogenic assay, which assesses the ability of single transformed cells to multiply and produce colonies, is described.

  10. Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis.

    Science.gov (United States)

    Ryan, Lisa K; Freeman, Katie B; Masso-Silva, Jorge A; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G; Fatahzadeh, Mahnaz; Scott, Richard W; Diamond, Gill

    2014-07-01

    There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.

  11. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

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    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  12. Microbial pathogens trigger host DNA double-strand breaks whose abundance is reduced by plant defense responses.

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    Junqi Song

    2014-04-01

    Full Text Available Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs in host plant DNA. DNA damage detected by histone γ-H2AX abundance or DNA comet assays arose hours before the disease-associated necrosis caused by virulent Pseudomonas syringae pv. tomato. Necrosis-inducing paraquat did not cause detectable DSBs at similar stages after application. Non-pathogenic E. coli and Pseudomonas fluorescens bacteria also did not induce DSBs. Elevation of reactive oxygen species (ROS is common during plant immune responses, ROS are known DNA damaging agents, and the infection-induced host ROS burst has been implicated as a cause of host DNA damage in animal studies. However, we found that DSB formation in Arabidopsis in response to P. syringae infection still occurs in the absence of the infection-associated oxidative burst mediated by AtrbohD and AtrbohF. Plant MAMP receptor stimulation or application of defense-activating salicylic acid or jasmonic acid failed to induce a detectable level of DSBs in the absence of introduced pathogens, further suggesting that pathogen activities beyond host defense activation cause infection-induced DNA damage. The abundance of infection-induced DSBs was reduced by salicylic acid and NPR1-mediated defenses, and by certain R gene-mediated defenses. Infection-induced formation of γ-H2AX still occurred in Arabidopsis atr/atm double mutants, suggesting the presence of an alternative mediator of pathogen-induced H2AX phosphorylation. In summary, pathogenic microorganisms can induce plant DNA damage. Plant defense mechanisms help to suppress rather than promote this damage, thereby contributing to the maintenance of genome integrity in somatic tissues.

  13. Obligate Biotroph Pathogens of the Genus Albugo Are Better Adapted to Active Host Defense Compared to Niche Competitors.

    Science.gov (United States)

    Ruhe, Jonas; Agler, Matthew T; Placzek, Aleksandra; Kramer, Katharina; Finkemeier, Iris; Kemen, Eric M

    2016-01-01

    Recent research suggested that plants behave differently under combined versus single abiotic and biotic stress conditions in controlled environments. While this work has provided a glimpse into how plants might behave under complex natural conditions, it also highlights the need for field experiments using established model systems. In nature, diverse microbes colonize the phyllosphere of Arabidopsis thaliana, including the obligate biotroph oomycete genus Albugo, causal agent of the common disease white rust. Biotrophic, as well as hemibiotrophic plant pathogens are characterized by efficient suppression of host defense responses. Lab experiments have even shown that Albugo sp. can suppress non-host resistance, thereby enabling otherwise avirulent pathogen growth. We asked how a pathogen that is vitally dependent on a living host can compete in nature for limited niche space while paradoxically enabling colonization of its host plant for competitors? To address this question, we used a proteomics approach to identify differences and similarities between lab and field samples of Albugo sp.-infected and -uninfected A. thaliana plants. We could identify highly similar apoplastic proteomic profiles in both infected and uninfected plants. In wild plants, however, a broad range of defense-related proteins were detected in the apoplast regardless of infection status, while no or low levels of defense-related proteins were detected in lab samples. These results indicate that Albugo sp. do not strongly affect immune responses and leave distinct branches of the immune signaling network intact. To validate our findings and to get mechanistic insights, we tested a panel of A. thaliana mutant plants with induced or compromised immunity for susceptibility to different biotrophic pathogens. Our findings suggest that the biotroph pathogen Albugo selectively interferes with host defense under different environmental and competitive pressures to maintain its ecological niche

  14. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.

    Science.gov (United States)

    Han, SeungHye; Mallampalli, Rama K

    2015-05-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications. PMID:25742123

  15. Depression as sickness behavior? A test of the host defense hypothesis in a high pathogen population.

    Science.gov (United States)

    Stieglitz, Jonathan; Trumble, Benjamin C; Thompson, Melissa Emery; Blackwell, Aaron D; Kaplan, Hillard; Gurven, Michael

    2015-10-01

    Sadness is an emotion universally recognized across cultures, suggesting it plays an important functional role in regulating human behavior. Numerous adaptive explanations of persistent sadness interfering with daily functioning (hereafter "depression") have been proposed, but most do not explain frequent bidirectional associations between depression and greater immune activation. Here we test several predictions of the host defense hypothesis, which posits that depression is part of a broader coordinated evolved response to infection or tissue injury (i.e. "sickness behavior") that promotes energy conservation and reallocation to facilitate immune activation. In a high pathogen population of lean and relatively egalitarian Bolivian forager-horticulturalists, we test whether depression and its symptoms are associated with greater baseline concentration of immune biomarkers reliably associated with depression in Western populations (i.e. tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and C-reactive protein [CRP]). We also test whether greater pro-inflammatory cytokine responses to ex vivo antigen stimulation are associated with depression and its symptoms, which is expected if depression facilitates immune activation. These predictions are largely supported in a sample of older adult Tsimane (mean±SD age=53.2±11.0, range=34-85, n=649) after adjusting for potential confounders. Emotional, cognitive and somatic symptoms of depression are each associated with greater immune activation, both at baseline and in response to ex vivo stimulation. The association between depression and greater immune activation is therefore not unique to Western populations. While our findings are not predicted by other adaptive hypotheses of depression, they are not incompatible with those hypotheses and future research is necessary to isolate and test competing predictions. PMID:26044086

  16. Saliva-Induced Clotting Captures Streptococci: Novel Roles for Coagulation and Fibrinolysis in Host Defense and Immune Evasion.

    Science.gov (United States)

    Wollein Waldetoft, Kristofer; Mohanty, Tirthankar; Karlsson, Christofer; Mörgelin, Matthias; Frick, Inga-Maria; Malmström, Johan; Björck, Lars

    2016-10-01

    Streptococcal pharyngitis is among the most common bacterial infections, but the molecular mechanisms involved remain poorly understood. Here we investigate the interactions among three major players in streptococcal pharyngitis: streptococci, plasma, and saliva. We find that saliva activates the plasma coagulation system through both the extrinsic and the intrinsic pathways, entrapping the bacteria in fibrin clots. The bacteria escape the clots by activating host plasminogen. Our results identify a potential function for the intrinsic pathway of coagulation in host defense and a corresponding role for fibrinolysis in streptococcal immune evasion. PMID:27456827

  17. Skin Electroporation of a Plasmid Encoding hCAP-18/LL-37 Host Defense Peptide Promotes Wound Healing

    OpenAIRE

    Steinstraesser, Lars; Lam, Martin C; Jacobsen, Frank; Porporato, Paolo E; Chereddy, Kiran Kumar; Becerikli, Mustafa; Stricker, Ingo; Hancock, Robert EW; Lehnhardt, Marcus; Sonveaux, Pierre; Préat, Véronique; Vandermeulen, Gaëlle

    2014-01-01

    Host defense peptides, in particular LL-37, are emerging as potential therapeutics for promoting wound healing and inhibiting bacterial growth. However, effective delivery of the LL-37 peptide remains limiting. We hypothesized that skin-targeted electroporation of a plasmid encoding hCAP-18/LL-37 would promote the healing of wounds. The plasmid was efficiently delivered to full-thickness skin wounds by electroporation and it induced expression of LL-37 in the epithelium. It significantly acce...

  18. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen, Candida albicans

    OpenAIRE

    Hise, Amy G.; Tomalka, Jeffrey; Ganesan, Sandhya; Patel, Krupen; Hall, Brian A.; Brown, Gordon D.; Fitzgerald, Katherine A.

    2009-01-01

    Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection we investigated the role of the proinflammatory cytokine IL-1β in host-defense to Candida albicans. We find that the synthesis, processing and release of IL-1β in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1 mediated...

  19. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents

    OpenAIRE

    Morash, Michael G.; Douglas, Susan E.; Anna Robotham; Ridley, Christina M.; Gallant, Jeffrey W.; Soanes, Kelly H.

    2011-01-01

    SUMMARY The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of actio...

  20. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents

    OpenAIRE

    Michael G. Morash; Douglas, Susan E.; Anna Robotham; Ridley, Christina M.; Gallant, Jeffrey W.; Soanes, Kelly H.

    2011-01-01

    SUMMARY The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of action. ...

  1. Induction of Porcine Host Defense Peptide Gene Expression by Short-Chain Fatty Acids and Their Analogs

    OpenAIRE

    Zeng, Xiangfang; Sunkara, Lakshmi T; Jiang, Weiyu; Bible, Megan; Carter, Scott; Ma, Xi; Qiao, Shiyan; Zhang, Guolong

    2013-01-01

    Dietary modulation of the synthesis of endogenous host defense peptides (HDPs) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes...

  2. NLRP7 and related inflammasome activating pattern recognition receptors and their function in host defense and disease.

    Science.gov (United States)

    Radian, Alexander D; de Almeida, Lucia; Dorfleutner, Andrea; Stehlik, Christian

    2013-01-01

    Host defense requires the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and the induction of pyroptotic cell death, which depends on the activation of inflammatory Caspases within inflammasomes by innate immune cells. Several cytosolic pattern recognition receptors (PRRs) have been implicated in this process in response to infectious and sterile agonists. Here we summarize the current knowledge on inflammasome-organizing PRRs, emphasizing the recently described NLRP7, and their implications in human disease.

  3. Geographically Distinct Expression Proifle of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

    Institute of Scientific and Technical Information of China (English)

    Guiying LING; Li LI; Jiuxiang GAO; Haining YU; Yipeng WANG; Jiang ZHOU

    2013-01-01

    Odorrana margaretae (Anura:Ranidae) is widely distributed in the southern provinces of China. Previously, 72 antimicrobial peptides (AMPs) belonging to 21 families were identiifed from the skin of O. margaretae, which were captured in the Hunan province. In the present study, ifve O. margaretae frogs were captured from the Guizhou province and a total of 28 cDNAs encoding 17 host defense peptides (HDPs) belonging to 14 families were cloned from the skin cDNA library of O. margaretae. Among the 17 HDPs, only one (brevinin-1-Omar5) had been characterized. The distinct HDP expression proifles for O. margaretae in the previous and present study may be attributed to the environmental differences between the sampling locations and the genetic divergence among O. margaretae populations. Besides, 11 of the 17 HDPs identiifed in the present study were novel for ranids. In order to understand their roles in host defense reactions, three HDPs (odorranain-H-OM1, odorranain-M-OM and ranatuerin-2-OM), which possess low sequence similarity with the known amphibian HDPs, were selected for further chemical synthesis and functional analysis. Odorranain-H-OM1 showed direct antimicrobial activity against bacteria and fungi. Odorranain-M-OM exhibited concentration-dependent anti-oxidant activity. Ranatuerin-2-OM showed lectin-like activity and could strongly hemagglu-tinate human intact erythrocytes with or without the presence of Ca2+. The diverse activities of HDPs implied that they may play different roles in host defense reactions of O. margaretae.

  4. ELR chemokine signaling in host defense and disease in a viral model of central nervous system disease

    Directory of Open Access Journals (Sweden)

    Martin P Hosking

    2014-06-01

    Full Text Available Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV into the central nervous system (CNS of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice that survive the acute stage of disease develop an immune-mediated demyelinating diseases characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Early following JHMV infection, there is a dynamic expression of chemokines and chemokine receptors that contribute to neuroinflammation by regulating innate and adaptive immune responses as well influencing glial biology. In response to JHMV infection, we have shown that signaling through the chemokine receptor CXCR2 contributes to host defense through recruitment of polymorphonuclear cells (PMNs to the CNS that enhance permeability of the blood-brain-barrier (BBB and facilitating entry of virus-specific T cells into the parenchyma. Further, CXCR2 promotes the protection of oligodendroglia from cytokine-induced apoptosis and restricts the severity of demyelination. This review covers aspects related to the role of CXCR2 in host defense and disease in response to JHMV infection.

  5. Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.

    Directory of Open Access Journals (Sweden)

    Lee R Haines

    Full Text Available BACKGROUND: Tropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. There is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. One new approach is to apply host defense peptides (HDP; formerly called antimicrobial peptides to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in their insect vectors. A potent anti-parasite effector is bovine myeloid antimicrobial peptide-27 (BMAP-27, a member of the cathelicidin family. Although BMAP-27 is a potent inhibitor of microbial growth, at higher concentrations it also exhibits cytotoxicity to mammalian cells. We tested the anti-parasite activity of BMAP-18, a truncated peptide that lacks the hydrophobic C-terminal sequence of the BMAP-27 parent molecule, an alteration that confers reduced toxicity to mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: BMAP-18 showed strong growth inhibitory activity against several species and life cycle stages of African trypanosomes, fish trypanosomes and Leishmania parasites in vitro. When compared to native BMAP-27, the truncated BMAP-18 peptide showed reduced cytotoxicity on a wide variety of mammalian and insect cells and on Sodalis glossindius, a bacterial symbiont of the tsetse vector. The fluorescent stain rhodamine 123 was used in immunofluorescence microscopy and flow cytometry experiments to show that BMAP-18 at low concentrations rapidly disrupted mitochondrial potential without obvious alteration of parasite plasma membranes, thus inducing death by apoptosis. Scanning electron microscopy revealed that higher concentrations of BMAP-18 induced membrane lesions in the parasites as early as 15 minutes after exposure, thus killing them by necrosis. In addition to direct killing of parasites, BMAP-18 was shown to inhibit LPS

  6. Cyclosporine A impairs nucleotide binding oligomerization domain (Nod1-mediated innate antibacterial renal defenses in mice and human transplant recipients.

    Directory of Open Access Journals (Sweden)

    Emilie Tourneur

    2013-01-01

    Full Text Available Acute pyelonephritis (APN, which is mainly caused by uropathogenic Escherichia coli (UPEC, is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA, decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN. We show that CsA-treated mice exhibit impaired production of the chemoattractant chemokines CXCL2 and CXCL1, decreased intrarenal recruitment of neutrophils, and greater susceptibility to UPEC than vehicle-treated mice. Strikingly, renal expression of Toll-like receptor 4 (Tlr4 and nucleotide-binding oligomerization domain 1 (Nod1, neutrophil migration capacity, and phagocytic killing of E. coli were significantly reduced in CsA-treated mice. CsA inhibited lipopolysaccharide (LPS-induced, Tlr4-mediated production of CXCL2 by epithelial collecting duct cells. In addition, CsA markedly inhibited Nod1 expression in neutrophils, macrophages, and renal dendritic cells. CsA, acting through inhibition of the nuclear factor of activated T-cells (NFATs, also markedly downregulated Nod1 in neutrophils and macrophages. Silencing the NFATc1 isoform mRNA, similar to CsA, downregulated Nod1 expression in macrophages, and administration of the 11R-VIVIT peptide inhibitor of NFATs to mice also reduced neutrophil bacterial phagocytosis and renal resistance to UPEC. Conversely, synthetic Nod1 stimulating agonists given to CsA-treated mice significantly increased renal resistance to UPEC. Renal transplant recipients receiving CsA exhibited similar decrease in NOD1 expression and neutrophil phagocytosis of E. coli. The findings suggest that such mechanism of NFATc1-dependent inhibition of Nod1-mediated innate immune response together with the decrease in Tlr4-mediated production of chemoattractant chemokines caused by Cs

  7. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Mathieu Blanc

    2011-03-01

    transcription level. The reduction in srebf2 gene transcription upon infection and IFN treatment is also found to be strictly dependent on ifnar1. Altogether these results show that type 1 IFN signaling is both necessary and sufficient for reducing the sterol metabolic network activity upon infection, thereby linking the regulation of the sterol pathway with interferon anti-viral defense responses. These findings bring a new link between sterol metabolism and interferon antiviral response and support the idea of using host metabolic modifiers of innate immunity as a potential antiviral strategy.

  8. Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Na; Zhu, Yongqun; Lu, Qiuhe; Hu, Liyan; Zheng, Yuqing; Shao, Feng (NIBS-China); (Zhejiang)

    2012-10-10

    Rab GTPases are frequent targets of vacuole-living bacterial pathogens for appropriate trafficking of the vacuole. Here we discover that bacterial effectors including VirA from nonvacuole Shigella flexneri and EspG from extracellular Enteropathogenic Escherichia coli (EPEC) harbor TBC-like dual-finger motifs and exhibits potent RabGAP activities. Specific inactivation of Rab1 by VirA/EspG disrupts ER-to-Golgi trafficking. S. flexneri intracellular persistence requires VirA TBC-like GAP activity that mediates bacterial escape from autophagy-mediated host defense. Rab1 inactivation by EspG severely blocks host secretory pathway, resulting in inhibited interleukin-8 secretion from infected cells. Crystal structures of VirA/EspG-Rab1-GDP-aluminum fluoride complexes highlight TBC-like catalytic role for the arginine and glutamine finger residues and reveal a 3D architecture distinct from that of the TBC domain. Structure of Arf6-EspG-Rab1 ternary complex illustrates a pathogenic signaling complex that rewires host Arf signaling to Rab1 inactivation. Structural distinctions of VirA/EspG further predict a possible extensive presence of TBC-like RabGAP effectors in counteracting various host defenses.

  9. A novel pathogenicity gene is required in the rice blast fungus to suppress the basal defenses of the host.

    Directory of Open Access Journals (Sweden)

    Myoung-Hwan Chi

    2009-04-01

    Full Text Available For successful colonization and further reproduction in host plants, pathogens need to overcome the innate defenses of the plant. We demonstrate that a novel pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses against host basal resistance. The DES1 gene was identified by screening for pathogenicity-defective mutants in a T-DNA insertional mutant library. Bioinformatic analysis revealed that this gene encodes a serine-rich protein that has unknown biochemical properties, and its homologs are strictly conserved in filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on developmental morphogenesis, including vegetative growth, conidial germination, appressorium formation, and appressorium-mediated penetration. Conidial size of the mutant became smaller than that of the wild type, but the mutant displayed no defects on cell wall integrity. The Deltades1 mutant was hypersensitive to exogenous oxidative stress and the activity and transcription level of extracellular enzymes including peroxidases and laccases were severely decreased in the mutant. In addition, ferrous ion leakage was observed in the Deltades1 mutant. In the interaction with a susceptible rice cultivar, rice cells inoculated with the Deltades1 mutant exhibited strong defense responses accompanied by brown granules in primary infected cells, the accumulation of reactive oxygen species (ROS, the generation of autofluorescent materials, and PR gene induction in neighboring tissues. The Deltades1 mutant displayed a significant reduction in infectious hyphal extension, which caused a decrease in pathogenicity. Notably, the suppression of ROS generation by treatment with diphenyleneiodonium (DPI, an inhibitor of NADPH oxidases, resulted in a significant reduction in the defense responses in plant tissues challenged with the Deltades1 mutant. Furthermore, the Deltades1 mutant recovered its normal infectious growth in DPI-treated plant tissues

  10. Lipooligosaccharide structure is an important determinant in the resistance of Neisseria gonorrhoeae to antimicrobial agents of innate host defense

    Directory of Open Access Journals (Sweden)

    Jacqueline T Balthazar

    2011-02-01

    Full Text Available The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS. We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS, could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal

  11. Secretory phospholipase A2 in dromedary tears: a host defense against staphylococci and other gram-positive bacteria.

    Science.gov (United States)

    Ben Bacha, Abir; Abid, Islem

    2013-03-01

    The best known physiologic function of secreted phospholipase A2 (sPLA2) group IIA (sPLA2-IIA) is defense against bacterial infection through hydrolytic degradation of bacterial membrane phospholipids. In fact, sPLA2-IIA effectively kills Gram-positive bacteria and to a lesser extent Gram-negative bacteria and is considered a major component of the eye's innate immune defense system. The antibacterial properties of sPLA2 have been demonstrated in rabbit and human tears. In this report, we have analyzed the bactericidal activity of dromedary tears and the subsequently purified sPLA2 on several Gram-positive bacteria. Our results showed that the sPLA2 displays a potent bactericidal activity against all the tested bacteria particularly against the Staphylococcus strains when tested in the ionic environment of tears. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2. Interestingly, lysozyme purified from dromedary tears showed a significant bactericidal activity against Listeria monocytogene and Staphylococcus epidermidis, whereas the one purified from human tears displayed no activity against these two strains. We have also demonstrated that Ca(2+) is crucial for the activity of dromedary tear sPLA2 and to a less extent Mg(2+) ions. Given the presence of sPLA2 in tears and intestinal secretions, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against Gram-positive bacteria.

  12. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    Directory of Open Access Journals (Sweden)

    Nadine T Nehme

    Full Text Available BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.

  13. Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  14. Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

    Directory of Open Access Journals (Sweden)

    Peter Sperisen

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  15. Relationships among CFTR expression, HCO3- secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies.

    Science.gov (United States)

    Shah, Viral S; Ernst, Sarah; Tang, Xiao Xiao; Karp, Philip H; Parker, Connor P; Ostedgaard, Lynda S; Welsh, Michael J

    2016-05-10

    Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Airway disease is the major source of morbidity and mortality. Successful implementation of gene- and cell-based therapies for CF airway disease requires knowledge of relationships among percentages of targeted cells, levels of CFTR expression, correction of electrolyte transport, and rescue of host defense defects. Previous studies suggested that, when ∼10-50% of airway epithelial cells expressed CFTR, they generated nearly wild-type levels of Cl(-) secretion; overexpressing CFTR offered no advantage compared with endogenous expression levels. However, recent discoveries focused attention on CFTR-mediated HCO3 (-) secretion and airway surface liquid (ASL) pH as critical for host defense and CF pathogenesis. Therefore, we generated porcine airway epithelia with varying ratios of CF and wild-type cells. Epithelia with a 50:50 mix secreted HCO3 (-) at half the rate of wild-type epithelia. Likewise, heterozygous epithelia (CFTR(+/-) or CFTR(+/∆F508)) expressed CFTR and secreted HCO3 (-) at ∼50% of wild-type values. ASL pH, antimicrobial activity, and viscosity showed similar relationships to the amount of CFTR. Overexpressing CFTR increased HCO3 (-) secretion to rates greater than wild type, but ASL pH did not exceed wild-type values. Thus, in contrast to Cl(-) secretion, the amount of CFTR is rate-limiting for HCO3 (-) secretion and for correcting host defense abnormalities. In addition, overexpressing CFTR might produce a greater benefit than expressing CFTR at wild-type levels when targeting small fractions of cells. These findings may also explain the risk of airway disease in CF carriers. PMID:27114540

  16. EBAG9 modulates host immune defense against tumor formation and metastasis by regulating cytotoxic activity of T lymphocytes

    OpenAIRE

    Miyazaki, T; Ikeda, K.; Horie-Inoue, K.; Kondo, T; Takahashi, S.; Inoue, S.

    2014-01-01

    Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a primary estrogen-responsive gene that we previously identified in MCF-7 breast cancer cells using the CpG genomic binding-site cloning technique. The expression of EBAG9 protein is often upregulated in malignant tumors, suggesting that this protein is involved in cancer pathophysiology. In the present study, we investigated the role of EBAG9 in host defense against implanted tumors in Ebag9-knockout (Ebag9KO) mice. MB-49 mou...

  17. Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

    Science.gov (United States)

    Warburton, Elizabeth M; Kam, Michael; Bar-Shira, Enav; Friedman, Aharon; Khokhlova, Irina S; Koren, Lee; Asfur, Mustafa; Geffen, Eli; Kiefer, Daniel; Krasnov, Boris R; Degen, A Allan

    2016-09-01

    Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system. PMID:27130319

  18. Differential control of pre-invasive and post-invasive antibacterial defense by the Arabidopsis circadian clock.

    Science.gov (United States)

    Korneli, Christin; Danisman, Selahattin; Staiger, Dorothee

    2014-09-01

    Plants show a suite of inducible defense responses against bacterial pathogens. Here we investigate in detail the effect of the circadian clock on these reactions in Arabidopsis thaliana. The magnitude of immune responses elicited by flg22, by virulent and by avirulent Pseudomonas syringae strains depends on the time of day of inoculation. The oxidative burst is stronger when flg22 is infiltrated in the morning in wild-type plants but not in the arrhythmic clock mutant lux arrhythmo/phytoclock1 (pcl1), and thus is controlled by the endogenous clock. Similarly, when bacteria are syringe-infiltrated into the leaf, defense gene induction is higher and bacterial growth is suppressed more strongly after morning inoculation in wild-type but not in pcl1 plants. Furthermore, cell death associated with the hypersensitive response was found to be under clock control. Notably, the clock effect depends on the mode of infection: upon spray inoculation onto the leaf surface, defense gene induction is higher and bacterial growth is suppressed more strongly upon evening inoculation. This different phasing of pre-invasive and post-invasive defense relates to clock-regulated stomatal movement. In particular, TIME FOR COFFEE may impact pathogen defense via clock-regulated stomata movement apart from its known role in time-of-day-dependent jasmonate responses. Taken together, these data highlight the importance of the circadian clock for the control of different immune responses at distinct times of the day. PMID:24974385

  19. Host-pathogen interactions between the human innate immune system and Candida albicans - Understanding and modeling defense and evasion strategies

    Directory of Open Access Journals (Sweden)

    Sybille eDühring

    2015-06-01

    Full Text Available The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given.

  20. Haematophagous arthropod saliva and host defense system: a tale of tear and blood

    Directory of Open Access Journals (Sweden)

    Andrade Bruno B.

    2005-01-01

    Full Text Available The saliva from blood-feeding arthropod vectors is enriched with molecules that display diverse functions that mediate a successful blood meal. They function not only as weapons against host's haemostatic, inflammatory and immune responses but also as important tools to pathogen establishment. Parasites, virus and bacteria taking advantage of vectors' armament have adapted to facilitate their entry in the host. Today, many salivary molecules have been identified and characterized as new targets to the development of future vaccines. Here we focus on current information on vector's saliva and the molecules responsible to modify host's hemostasis and immune response, also regarding their role in disease transmission.

  1. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

    NARCIS (Netherlands)

    Smeekens, Sanne P.; Ng, Aylwin; Kumar, Vinod; Johnson, Melissa D.; Plantinga, Theo S.; van Diemen, Cleo; Arts, Peer; Verwiel, Eugene T. P.; Gresnigt, Mark S.; Fransen, Karin; van Sommeren, Suzanne; Oosting, Marije; Cheng, Shih-Chin; Joosten, Leo A. B.; Hoischen, Alexander; Kullberg, Bart-Jan; Scott, William K.; Perfect, John R.; van der Meer, Jos W. M.; Wijmenga, Cisca; Netea, Mihai G.; Xavier, Ramnik J.

    2013-01-01

    Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candid

  2. Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor

    OpenAIRE

    Miguel A. Mata; Satterly, Neal; Versteeg, Gijs A.; Frantz, Doug; Wei, Shuguang; Williams, Noelle; Schmolke, Mirco; Peña-Llopis, Samuel; Brugarolas, James; Forst, Christian V.; White, Michael A.; García-Sastre, Adolfo; Roth, Michael G.; Fontoura, Beatriz M.A.

    2011-01-01

    A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occu...

  3. Chemical Inhibition of RNA Viruses Reveals REDD1 as Host Defense Factor

    OpenAIRE

    Miguel A. Mata; Satterly, Neal; Versteeg, Gijs A.; Frantz, Doug; Wei, Shuguang; Williams, Noelle; Schmolke, Mirco; Pena-Llopis, Samuel; Brugarolas, James; Forst, Christian; White, Michael A.; Garcia-Sastre, Adolfo; Roth, Michael G.; Fontoura, Beatriz M.A.

    2011-01-01

    A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reverted NS1-mediated inhibition of host gene expression. A counter-screen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus. The mechanism of action was throu...

  4. Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses.

    Science.gov (United States)

    Gay, Gabrielle; Braun, Laurence; Brenier-Pinchart, Marie-Pierre; Vollaire, Julien; Josserand, Véronique; Bertini, Rose-Laurence; Varesano, Aurélie; Touquet, Bastien; De Bock, Pieter-Jan; Coute, Yohann; Tardieux, Isabelle; Bougdour, Alexandre; Hakimi, Mohamed-Ali

    2016-08-22

    An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-γ activates a variety of T. gondii-targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-γ defenses by interfering with the transcription of IFN-γ-stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1(+) inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-γ-mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism. PMID:27503074

  5. Review: The intersection of surfactant homeostasis and innate host defense of the lung: lessons from newborn infants.

    Science.gov (United States)

    Whitsett, Jeffrey A

    2010-06-01

    The study of pulmonary surfactant, directed towards prevention and treatment of respiratory distress syndrome in preterm infants, led to the identification of novel proteins/genes that determine the synthesis, packaging, secretion, function, and catabolism of alveolar surfactant. The surfactant proteins, SP-A, SP-B, SP-C, and SP-D, and the surfactant lipid associated transporter, ABCA3, play critical roles in surfactant homeostasis. The study of their structure and function provided insight into a system that integrates the biophysical need to reduce surface tension in the alveoli and the innate host defenses required to maintain pulmonary structure and function after birth. Alveolar homeostasis depends on the intrinsic, multifunctional structures of the surfactant-associated proteins and the shared transcriptional regulatory modules that determine both the expression of genes involved in surfactant production as well as those critical for host defense. Identification of the surfactant proteins and the elucidation of the genetic networks regulating alveolar homeostasis have provided the basis for understanding and diagnosing rare and common pulmonary disorders, including respiratory distress syndrome, inherited disorders of surfactant homeostasis, and pulmonary alveolar proteinosis. PMID:20351134

  6. Important role for Toll-like receptor 9 in host defense against meningococcal sepsis

    DEFF Research Database (Denmark)

    Sjölinder, Hong; Mogensen, Trine; Kilian, Mogens;

    2008-01-01

    Neisseria meningitidis is a leading cause of meningitis and sepsis. The pathogenesis of meningococcal disease is determined by both bacterial virulence factors and the host inflammatory response. Toll-like receptors (TLRs) are prominent activators of the inflammatory response, and TLR2, -4, and -9...... have been reported to be involved in the host response to N. meningitidis. While TLR4 has been suggested to play an important role in early containment of infection, the roles of TLR2 and TLR9 in meningococcal disease are not well described. Using a model for meningococcal sepsis, we report that TLR9...

  7. Increased host investment in extrafloral nectar (EFN improves the efficiency of a mutualistic defensive service.

    Directory of Open Access Journals (Sweden)

    Marcia González-Teuber

    Full Text Available Extrafloral nectar (EFN plays an important role as plant indirect defence through the attraction of defending ants. Like all rewards produced in the context of a mutualism, however, EFN is in danger of being exploited by non-ant consumers that do not defend the plant against herbivores. Here we asked whether plants, by investing more in EFN, can improve their indirect defence, or rather increase the risk of losing this investment to EFN thieves. We used the obligate plant-ant Acacia-Pseudomyrmex system and examined experimentally in the field during the dry and the rainy seasons how variations in EFN secretion are related to (i ant activity, to (ii the ant-mediated defence against herbivores and (iii the exploitation of EFN by non-ant consumers. Extrafloral investment enhanced ant recruitment and was positively related to the ant mediated defence against herbivores. The ant-mediated protection from exploiters also increased in proportion to the nectar sugar concentration. Although the daily peak of EFN production coincided with the highest activity of EFN thieves, Pseudomyrmex ferrugineus ants protected this resource effectively from exploiters. Nevertheless, the defensive effects by ants differed among seasons. During the dry season, plants grew slower and secreted more EFN than in the rainy season, and thus, experienced a higher level of ant-mediated indirect defence. Our results show that an increased plant investment in an indirect defence trait can improve the resulting defensive service against both herbivores and exploiters. EFN secretion by obligate ant-plants represents a defensive trait for which the level of investment correlates positively with the beneficial effects obtained.

  8. In vitro and ex vivo effects of cyclosporin A on phagocytic host defenses against Aspergillus fumigatus.

    OpenAIRE

    Roilides, E.; Robinson, T.; T Sein; Pizzo, P A; Walsh, T J

    1994-01-01

    Because cyclosporin A (CsA) is extensively used as an immunosuppressive agent, its effects on phagocytic defenses against Aspergillus fumigatus were studied in vitro and ex vivo. After incubation with 10 to 250 ng of CsA per ml at 37 degrees C for 60 min, polymorphonuclear leukocytes (PMNs) exhibited unaltered superoxide anion (O2-) production in response to phorbol myristate acetate and N-formylmethionyl leucyl phenylalanine, whereas > or = 500 ng/ml significantly suppressed it (P < 0.01). M...

  9. Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

    Directory of Open Access Journals (Sweden)

    Matthew A Crawford

    Full Text Available Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.

  10. LPS inmobilization on porous and non-porous supports as an approach for the isolation of anti-LPS host-defense peptides.

    Directory of Open Access Journals (Sweden)

    Carlos eLopez-Abarrategui

    2013-12-01

    Full Text Available Lipopolysaccharides (LPS are the major molecular component of the outer membrane of Gram-negative bacteria. This molecule is recognized as a sign of bacterial infection, responsible for the development of local inflammatory response and, in extreme cases, septic shock. Unfortunately, despite substantial advances in the pathophysiology of sepsis, there is no efficacious therapy against this syndrome yet. As a consequence, septic shock syndrome continues to increase, reaching mortality rates over 50% in some cases. Even though many preclinical studies and clinical trials have been conducted, there is no FDA-approved drug yet that interacts directly against LPS. Cationic host defense peptides could be an alternative solution since they possess both antimicrobial and antiseptic properties. Host defense peptides are small, positively charged peptides which are evolutionarily conserved components of the innate immune response. In fact, binding to diverse chemotypes of LPS and inhibition of LPS-induced pro-inflammatory cytokines from macrophages have been demonstrated for different host defense peptides (HDPs. Curiously, none of them have been isolated by their affinity to LPS. A diversity of supports could be useful for such biological interaction and suitable for isolating host defense peptides that recognize LPS. This approach could expand the rational search for anti-LPS host defense peptides.

  11. Host defense pathways against fungi: the basis for vaccines and immunotherapy

    Directory of Open Access Journals (Sweden)

    Agostinho eCarvalho

    2012-05-01

    Full Text Available Fungal vaccines have long been a goal in the fields of immunology and microbiology to counter the high mortality and morbidity rates owing to fungal diseases, particularly in immunocompromised patients. However, the design of effective vaccination formulations for durable protection to the different fungi has lagged behind due to the important differences among fungi and their biology and our limited understanding of the complex host-pathogen interactions and immune responses. Overcoming these challenges is expected to contribute to improved vaccination strategies aimed at personalized efficacy across distinct target patient populations. This likely requires the integration of multifaceted approaches encompassing advanced immunology, systems biology, immunogenetics and bioinformatics in the fields of fungal and host biology and their reciprocal interactions.

  12. Root border cells and secretions as critical elements in plant host defense.

    Science.gov (United States)

    Driouich, Azeddine; Follet-Gueye, Marie-Laure; Vicré-Gibouin, Maïté; Hawes, Martha

    2013-08-01

    Border cells and border-like cells are released from the root tip as individual cells and small aggregates, or as a group of attached cells. These are viable components of the root system that play a key role in controlling root interaction with living microbes of the rhizosphere. As their separation from root tip proceeds, the cells synthesize and secrete a hydrated mucilage that contains polysaccharides, secondary metabolites, antimicrobial proteins and extracellular DNA (exDNA). This exDNA-based matrix seems to function in root defense in a way similar to that of recently characterized neutrophil extracellular traps (NETs) in mammalian cells. This review discusses the role of the cells and secreted compounds in the protection of root tip against microbial infections.

  13. Using antimicrobial host defense peptides as anti-infective and immunomodulatory agents.

    Science.gov (United States)

    Kruse, Thomas; Kristensen, Hans-Henrik

    2008-12-01

    Virtually all life forms express short antimicrobial cationic peptides as an important component of their innate immune defenses. They serve as endogenous antibiotics that are able to rapidly kill an unusually broad range of bacteria, fungi and viruses. Consequently, considerable efforts have been expended to exploit the therapeutic potential of these antimicrobial peptides. Within the last couple of years, it has become increasingly clear that many of these peptides, in addition to their direct antimicrobial activity, also have a wide range of functions in modulating both innate and adaptive immunity. For one class of antimicrobial peptides, such as the human defensins, their primary role may even be as immunomodulators. These properties potentially provide entirely new therapeutic approaches to anti-infective therapy.

  14. Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment.

    Science.gov (United States)

    Wikel, Stephen

    2013-01-01

    Ticks are unique among hematophagous arthropods by continuous attachment to host skin and blood feeding for days; complexity and diversity of biologically active molecules differentially expressed in saliva of tick species; their ability to modulate the host defenses of pain and itch, hemostasis, inflammation, innate and adaptive immunity, and wound healing; and, the diverse array of infectious agents they transmit. All of these interactions occur at the cutaneous interface in a complex sequence of carefully choreographed host defense responses and tick countermeasures resulting in an environment that facilitates successful blood feeding and establishment of tick-borne infectious agents within the host. Here, we examine diverse patterns of tick attachment to host skin, blood feeding mechanisms, salivary gland transcriptomes, bioactive molecules in tick saliva, timing of pathogen transmission, and host responses to tick bite. Ticks engage and modulate cutaneous and systemic immune defenses involving keratinocytes, natural killer cells, dendritic cells, T cell subpopulations (Th1, Th2, Th17, Treg), B cells, neutrophils, mast cells, basophils, endothelial cells, cytokines, chemokines, complement, and extracellular matrix. A framework is proposed that integrates tick induced changes of skin immune effectors with their ability to respond to tick-borne pathogens. Implications of these changes are addressed. What are the consequences of tick modulation of host cutaneous defenses? Does diversity of salivary gland transcriptomes determine differential modulation of host inflammation and immune defenses and therefore, in part, the clades of pathogens effectively transmitted by different tick species? Do ticks create an immunologically modified cutaneous environment that enhances specific pathogen establishment? Can tick saliva molecules be used to develop vaccines that block pathogen transmission? PMID:24312085

  15. Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment

    Directory of Open Access Journals (Sweden)

    Stephen eWikel

    2013-11-01

    Full Text Available Ticks are unique among hematophagous arthropods by continuous attachment to host skin and blood feeding for days; complexity and diversity of biologically active molecules differentially expressed in saliva of tick species; their ability to modulate the host defenses of pain and itch, hemostasis, inflammation, innate and adaptive immunity, and wound healing; and, the diverse array of infectious agents they transmit. All of these interactions occur at the cutaneous interface in a complex sequence of carefully choreographed host defense responses and tick countermeasures resulting in an environment that facilitates successful blood feeding and establishment of tick-borne infectious agents within the host. Here, we examine diverse patterns of tick attachment to host skin, blood feeding mechanisms, salivary gland transcriptomes, bioactive molecules in tick saliva, timing of pathogen transmission, and host responses to tick bite. Ticks engage and modulate cutaneous and systemic immune defenses involving keratinocytes, natural killer cells, dendritic cells, T cell subpopulations (Th1, Th2, Th17, Treg , B cells, neutrophils, mast cells, basophils, endothelial cells, cytokines, chemokines, complement, and extracellular matrix. A framework is proposed that integrates tick induced changes of skin immune effectors with their ability to respond to tick-borne pathogens. Implications of these changes are addressed. What are the consequences of tick modulation of host cutaneous defenses? Does diversity of salivary gland transcriptomes determine differential modulation of host inflammation and immune defenses and therefore, in part, the clades of pathogens effectively transmitted by different tick species? Do ticks create an immunologically modified cutaneous environment that enhances specific pathogen establishment? Can tick saliva molecules be used to develop vaccines that block pathogen transmission?

  16. NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense.

    Science.gov (United States)

    Franchi, Luigi; Kamada, Nobuhiko; Nakamura, Yuumi; Burberry, Aaron; Kuffa, Peter; Suzuki, Shiho; Shaw, Michael H; Kim, Yun-Gi; Núñez, Gabriel

    2012-05-01

    Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we found that intestinal phagocytes were anergic to ligands for Toll-like receptors (TLRs) or commensals but constitutively expressed the precursor to interleukin 1β (pro-IL-1β). After infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produced mature IL-1β through the NLRC4 inflammasome but did not produce tumor necrosis factor (TNF) or IL-6. BALB/c mice deficient in NLRC4 or the IL-1 receptor were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. That enhanced lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment and poor intestinal pathogen clearance. Thus, NLRC4-dependent production of IL-1β by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine. PMID:22484733

  17. NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense

    Science.gov (United States)

    Franchi, Luigi; Kamada, Nobuhiko; Nakamura, Yuumi; Burberry, Aaron; Kuffa, Peter; Suzuki, Shiho; Shaw, Michael H.; Kim, Yun-Gi; Núñez, Gabriel

    2012-01-01

    Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we report that intestinal phagocytes are anergic to Toll-like receptor ligands or commensals, but constitutively express pro-interleukin-1β (proIL-1β). Upon infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produce mature IL-1β through the NLRC4 inflammasome, but not tumor necrosis factor or IL-6. Mice deficient in NLRC4 or IL-1 receptor on a Balb/c background were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. Increased lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment, and poor intestinal pathogen clearance. Thus, NLRC4-dependent IL-1β production by intestinal phagocytes represents a specific response discriminating pathogenic from commensal bacteria and contributes to host defense in the intestine. PMID:22484733

  18. Parallel activities and interactions between antimicrobial peptides and complement in host defense at the airway epithelial surface.

    Science.gov (United States)

    Hiemstra, Pieter S

    2015-11-01

    Antimicrobial peptides and complement components contribute to host defense as well as inflammation and tissue injury in the respiratory tract. The airway epithelial surface is the main site of action of these immune effectors, and airway epithelial cells contribute markedly to their local production. Whereas both antimicrobial peptides and complement display overlapping functions, it is increasingly clear that both effector mechanisms also interact. Furthermore, excessive or uncontrolled release of antimicrobial peptides as well as complement activation may contribute to inflammatory lung diseases. Therefore, further knowledge of interactions between these systems may provide more insight into the pathogenesis of a range of lung diseases. In this review, recent findings on the functions, collaborations and other interactions between antimicrobial peptides and complement are discussed with a specific focus on the airway epithelium.

  19. Comprehensive transcript profiling of Pto- and Prf-mediated host defense responses to infection by Pseudomonas syringae pv. tomato.

    Science.gov (United States)

    Mysore, Kirankumar S; Crasta, Oswald R; Tuori, Robert P; Folkerts, Otto; Swirsky, Peter B; Martin, Gregory B

    2002-11-01

    The disease resistance gene Pto encodes a serine/threonine protein kinase that confers resistance in tomato to Pseudomonas syringae pv. tomato strains that express the effector protein AvrPto. Pto-mediated resistance to bacterial speck disease also requires Prf, a protein with leucine-rich repeats and a putative nucleotide-binding site, although the role of Prf in the defense pathway is not known. We used GeneCalling, an open-architecture, mRNA-profiling technology, to identify genes that are either induced or suppressed in leaves 4 h after bacterial infection in the Pto- and Prf-mediated tomato-Pseudomonas(avrPto) interaction. Over 135 000 individual cDNA fragments representing an estimated 90% of the transcripts expressed in tomato leaves were examined and 432 differentially expressed genes were identified. The genes encode over 25 classes of proteins including 11 types of transcription factors and many signal transduction components. Differential expression of 91% of the genes required both Pto and Prf. Interestingly, differential expression of 32 genes did not require Pto but was dependent on Prf. Thus, our data support a role for Prf early in the Pto pathway and indicate that Prf can also function as an independent host recognition determinant of bacterial infection. Comprehensive expression profiling of the Pto-mediated defense response allows the development of many new hypotheses about the molecular basis of resistance to bacterial speck disease.

  20. Pseudomonas fluorescens induces strain-dependent and strain-independent host plant responses in defense networks, primary metabolism and photosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Dale A [ORNL; Morrell-Falvey, Jennifer L [ORNL; Karve, Abhijit A [ORNL; Lu, Tse-Yuan S [ORNL; Tschaplinski, Timothy J [ORNL; Tuskan, Gerald A [ORNL; Chen, Jay [ORNL; Martin, Madhavi Z [ORNL; Jawdy, Sara [ORNL; Weston, David [ORNL; Doktycz, Mitchel John [ORNL; Schadt, Christopher Warren [ORNL

    2012-01-01

    Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root-microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

  1. Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1.

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    Eric J Haas-Stapleton

    Full Text Available Candida albicans is an opportunistic fungal pathogen of humans that resides commensally on epithelial surfaces, but can cause inflammation when pathogenic. Resolvins are a class of anti-inflammatory lipids derived from omega-3 polyunsaturated fatty acids (PUFA that attenuate neutrophil migration during the resolution phase of inflammation. In this report we demonstrate that C. albicans biosynthesizes resolvins that are chemically identical to those produced by human cells. In contrast to the trans-cellular biosynthesis of human Resolvin E1 (RvE1, RvE1 biosynthesis in C. albicans occurs in the absence of other cellular partners. C. albicans biosynthesis of RvE1 is sensitive to lipoxygenase and cytochrome P450 monoxygenase inhibitors. We show that 10nM RvE1 reduces neutrophil chemotaxis in response to IL-8; 1nM RvE1 enhanced phagocytosis of Candida by human neutrophils, as well as intracellular ROS generation and killing, while having no direct affect on neutrophil motility. In a mouse model of systemic candidiasis, RvE1 stimulated clearance of the fungus from circulating blood. These results reveal an inter-species chemical signaling system that modulates host immune functions and may play a role in balancing host carriage of commensal and pathogenic C. albicans.

  2. Lipopolysaccharide neutralization by antimicrobial peptides: a gambit in the innate host defense strategy.

    Science.gov (United States)

    Pulido, David; Nogués, M Victòria; Boix, Ester; Torrent, Marc

    2012-01-01

    Antimicrobial peptides (AMPs) are nowadays understood as broad multifunctional tools of the innate immune system to fight microbial infections. In addition to its direct antimicrobial action, AMPs can modulate the host immune response by promoting or restraining the recruitment of cells and chemicals to the infection focus. Binding of AMPs to lipopolysaccharide is a critical step for both their antimicrobial action and their immunomodulatory properties. On the one hand, removal of Gram-negative bacteria by AMPs can be an effective strategy to prevent a worsened inflammatory response that may lead to septic shock. On the other hand, by neutralizing circulating endotoxins, AMPs can successfully reduce nitric oxide and tumor necrosis factor-α production, hence preventing severe tissue damage. Furthermore, AMPs can also interfere with the Toll-like receptor 4 recognition system, suppressing cytokine production and contributing to modulate the inflammatory response. Here, we review the immune system strategies devised by AMPs to avoid an exacerbated inflammatory response and thus prevent a fatal end to the host.

  3. The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense.

    Science.gov (United States)

    van Esse, H Peter; Van't Klooster, John W; Bolton, Melvin D; Yadeta, Koste A; van Baarlen, Peter; Boeren, Sjef; Vervoort, Jacques; de Wit, Pierre J G M; Thomma, Bart P H J

    2008-07-01

    Cladosporium fulvum (syn. Passalora fulva) is a biotrophic fungal pathogen that causes leaf mold of tomato (Solanum lycopersicum). During growth in the apoplast, the fungus establishes disease by secreting effector proteins, 10 of which have been characterized. We have previously shown that the Avr2 effector interacts with the apoplastic tomato Cys protease Rcr3, which is required for Cf-2-mediated immunity. We now show that Avr2 is a genuine virulence factor of C. fulvum. Heterologous expression of Avr2 in Arabidopsis thaliana causes enhanced susceptibility toward extracellular fungal pathogens, including Botrytis cinerea and Verticillium dahliae, and microarray analysis showed that Avr2 expression triggers a global transcriptome reflecting pathogen challenge. Cys protease activity profiling showed that Avr2 inhibits multiple extracellular Arabidopsis Cys proteases. In tomato, Avr2 expression caused enhanced susceptibility toward Avr2-defective C. fulvum strains and also toward B. cinerea and V. dahliae. Cys protease activity profiling in tomato revealed that, in this plant also, Avr2 inhibits multiple extracellular Cys proteases, including Rcr3 and its close relative Pip1. Finally, silencing of Avr2 significantly compromised C. fulvum virulence on tomato. We conclude that Avr2 is a genuine virulence factor of C. fulvum that inhibits several Cys proteases required for plant basal defense.

  4. P58(IPK: a novel "CIHD" member of the host innate defense response against pathogenic virus infection.

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    Alan G Goodman

    2009-05-01

    Full Text Available To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58(IPK, a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2alpha kinase, PKR. Here, we report that infection of P58(IPK knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58(IPK in the antiviral response. Our results suggest that P58(IPK represents a new class of molecule, a cellular inhibitor of the host defense (CIHD, as P58(IPK is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.

  5. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

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    Tijmen J Hommes

    Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  6. Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (Melioidosis.

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    W Joost Wiersinga

    2007-07-01

    Full Text Available BACKGROUND: Toll-like receptors (TLRs are essential in host defense against pathogens by virtue of their capacity to detect microbes and initiate the immune response. TLR2 is seen as the most important receptor for gram-positive bacteria, while TLR4 is regarded as the gram-negative TLR. Melioidosis is a severe infection caused by the gram-negative bacterium, Burkholderia pseudomallei, that is endemic in Southeast Asia. We aimed to characterize the expression and function of TLRs in septic melioidosis. METHODS AND FINDINGS: Patient studies: 34 patients with melioidosis demonstrated increased expression of CD14, TLR1, TLR2, and TLR4 on the cell surfaces of monocytes and granulocytes, and increased CD14, TLR1, TLR2, TLR4, LY96 (also known as MD-2, TLR5, and TLR10 mRNA levels in purified monocytes and granulocytes when compared with healthy controls. In vitro experiments: Whole-blood and alveolar macrophages obtained from TLR2 and TLR4 knockout (KO mice were less responsive to B. pseudomallei in vitro, whereas in the reverse experiment, transfection of HEK293 cells with either TLR2 or TLR4 rendered these cells responsive to this bacterium. In addition, the lipopolysaccharide (LPS of B. pseudomallei signals through TLR2 and not through TLR4. Mouse studies: Surprisingly, TLR4 KO mice were indistinguishable from wild-type mice with respect to bacterial outgrowth and survival in experimentally induced melioidosis. In contrast, TLR2 KO mice displayed a markedly improved host defenses as reflected by a strong survival advantage together with decreased bacterial loads, reduced lung inflammation, and less distant-organ injury. CONCLUSIONS: Patients with melioidosis displayed an up-regulation of multiple TLRs in peripheral blood monocytes and granulocytes. Although both TLR2 and TLR4 contribute to cellular responsiveness to B. pseudomallei in vitro, TLR2 detects the LPS of B. pseudomallei, and only TLR2 impacts on the immune response of the intact host in

  7. Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment

    OpenAIRE

    Stephen eWikel

    2013-01-01

    Ticks are unique among hematophagous arthropods by continuous attachment to host skin and blood feeding for days; complexity and diversity of biologically active molecules differentially expressed in saliva of tick species; their ability to modulate the host defenses of pain and itch, hemostasis, inflammation, innate and adaptive immunity, and wound healing; and, the diverse array of infectious agents they transmit. All of these interactions occur at the cutaneous interface in a complex seque...

  8. Porcine antimicrobial peptides: new prospects for ancient molecules of host defense.

    Science.gov (United States)

    Zhang, G; Ross, C R; Blecha, F

    2000-01-01

    Antimicrobial peptides (AMPs) are small, endogenous, polycationic molecules that constitute a ubiquitous and significant component of innate immunity. These natural antibiotics have broad microbicidal activity against various bacteria, fungi, and enveloped viruses. Because most AMPs kill bacteria by physical disruption of cell membranes, which may prevent microorganisms from developing resistance against these agents, they are being explored as possible alternatives to conventional antibiotics. Pigs, like many other mammals, produce an impressive array of AMPs, which are synthesized predominantly by host leukocytic phagocytes or mucosal epithelial cells. Currently, more than a dozen distinct porcine AMPs have been identified and a majority belongs to the cathelicidin family. This review briefly summarizes recent advances in porcine AMP research with an emphasis on the diverse biological functions of each peptide. Mechanisms of action of these AMPs and their role in the resistance to infections are considered. Finally, the current status of pharmaceutical and agricultural uses of AMPs as well as future prospects for their application in the food animal industry is discussed.

  9. A Comparative Study of Lung Host Defense in Murine Obesity Models. Insights into Neutrophil Function.

    Science.gov (United States)

    Ubags, Niki D J; Burg, Elianne; Antkowiak, Maryellen; Wallace, Aaron M; Dilli, Estee; Bement, Jenna; Wargo, Matthew J; Poynter, Matthew E; Wouters, Emiel F M; Suratt, Benjamin T

    2016-08-01

    We have shown that obesity-associated attenuation of murine acute lung injury is driven, in part, by blunted neutrophil chemotaxis, yet differences were noted between the two models of obesity studied. We hypothesized that obesity-associated impairment of multiple neutrophil functions contributes to increased risk for respiratory infection but that such impairments may vary between murine models of obesity. We examined the most commonly used murine obesity models (diet-induced obesity, db/db, CPE(fat/fat), and ob/ob) using a Klebsiella pneumoniae pneumonia model and LPS-induced pneumonitis. Marrow-derived neutrophils from uninjured lean and obese mice were examined for in vitro functional responses. All obesity models showed impaired clearance of K. pneumoniae, but in differing temporal patterns. Failure to contain infection in obese mice was seen in the db/db model at both 24 and 48 hours, yet this defect was only evident at 24 hours in CPE(fat/fat) and ob/ob models, and at 48 hours in diet-induced obesity. LPS-induced airspace neutrophilia was decreased in all models, and associated with blood neutropenia in the ob/ob model but with leukocytosis in the others. Obese mouse neutrophils from all models demonstrated impaired chemotaxis, whereas neutrophil granulocyte colony-stimulating factor-mediated survival, LPS-induced cytokine transcription, and mitogen-activated protein kinase and signal transducer and activator of transcription 3 activation in response to LPS and granulocyte colony-stimulating factor, respectively, were variably impaired across the four models. Obesity-associated impairment of host response to lung infection is characterized by defects in neutrophil recruitment and survival. However, critical differences exist between commonly used mouse models of obesity and may reflect variable penetrance of elements of the metabolic syndrome, as well as other factors. PMID:27128821

  10. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    Science.gov (United States)

    Sussan, Thomas E; Gajghate, Sachin; Thimmulappa, Rajesh K; Ma, Jinfang; Kim, Jung-Hyun; Sudini, Kuladeep; Consolini, Nicola; Cormier, Stephania A; Lomnicki, Slawo; Hasan, Farhana; Pekosz, Andrew; Biswal, Shyam

    2015-01-01

    Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11) free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections. PMID:25651083

  11. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    Directory of Open Access Journals (Sweden)

    Thomas E Sussan

    Full Text Available Electronic cigarettes (E-cigs have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.

  12. Characterization of a variant of Xanthomonas citri subsp. citri that triggers a host-specific defense response.

    Science.gov (United States)

    Chiesa, María A; Siciliano, María F; Ornella, Leonardo; Roeschlin, Roxana A; Favaro, María A; Delgado, Natalia Pino; Sendín, Lorena N; Orce, Ingrid G; Ploper, L Daniel; Vojnov, Adrian A; Vacas, José Gadea; Filippone, María P; Castagnaro, Atilio P; Marano, María R

    2013-06-01

    Citrus is an economically important fruit crop that is severely afflicted by Asiatic citrus bacterial canker (CBC), a disease caused by the phytopathogen Xanthomonas citri subsp. citri (X. citri). To gain insight into the molecular epidemiology of CBC, 42 Xanthomonas isolates were collected from a range of Citrus spp. across 17 different orchards in Tucumán, Argentina and subjected to molecular, biochemical, and pathogenicity tests. Analysis of genome-specific X. citri markers and DNA polymorphisms based on repetitive elements-based polymerase chain reaction showed that all 42 isolates belonged to X. citri. Interestingly, pathogenicity tests showed that one isolate, which shares >90% genetic similarity to the reference strain X. citri T, has host range specificity. This new variant of X. citri subsp. citri, named X. citri A(T), which is deficient in xanthan production, induces an atypical, noncankerous chlorotic phenotype in Citrus limon and C. paradisi and weak cankerous lesions in C. aurantifolia and C. clementina leaves. In C. limon, suppression of canker development is concomitant with an oxidative burst; xanthan is not implicated in the phenotype induced by this interaction, suggesting that other bacterial factors would be involved in triggering the defense response.

  13. The Hexahistidine Motif of Host-Defense Protein Human Calprotectin Contributes to Zinc Withholding and Its Functional Versatility.

    Science.gov (United States)

    Nakashige, Toshiki G; Stephan, Jules R; Cunden, Lisa S; Brophy, Megan Brunjes; Wommack, Andrew J; Keegan, Brenna C; Shearer, Jason M; Nolan, Elizabeth M

    2016-09-21

    Human calprotectin (CP, S100A8/S100A9 oligomer, MRP-8/MRP-14 oligomer) is an abundant host-defense protein that is involved in the metal-withholding innate immune response. CP coordinates a variety of divalent first-row transition metal ions, which is implicated in its antimicrobial function, and its ability to sequester nutrient Zn(II) ions from microbial pathogens has been recognized for over two decades. CP has two distinct transition-metal-binding sites formed at the S100A8/S100A9 dimer interface, including a histidine-rich site composed of S100A8 residues His17 and His27 and S100A9 residues His91 and His95. In this study, we report that CP binds Zn(II) at this site using a hexahistidine motif, completed by His103 and His105 of the S100A9 C-terminal tail and previously identified as the high-affinity Mn(II) and Fe(II) coordination site. Zn(II) binding at this unique site shields the S100A9 C-terminal tail from proteolytic degradation by proteinase K. X-ray absorption spectroscopy and Zn(II) competition titrations support the formation of a Zn(II)-His6 motif. Microbial growth studies indicate that the hexahistidine motif is important for preventing microbial Zn(II) acquisition from CP by the probiotic Lactobacillus plantarum and the opportunistic human pathogen Candida albicans. The Zn(II)-His6 site of CP expands the known biological coordination chemistry of Zn(II) and provides new insight into how the human innate immune system starves microbes of essential metal nutrients. PMID:27541598

  14. Characterization of Oyster Voltage-Dependent Anion Channel 2 (VDAC2) Suggests Its Involvement in Apoptosis and Host Defense.

    Science.gov (United States)

    Li, Yingxiang; Zhang, Linlin; Qu, Tao; Li, Li; Zhang, Guofan

    2016-01-01

    Genomic and transcriptomic studies have revealed a sophisticated and powerful apoptosis regulation network in oyster, highlighting its adaptation to sessile life in a highly stressful intertidal environment. However, the functional molecular basis of apoptosis remains largely unexplored in oysters. In this study, we focused on a representative apoptotic gene encoding voltage-dependent anion channel 2 (VDAC2), a porin that abounds at the mitochondrial outer membrane. This is the first report on the identification and characterization of a VDAC gene in the Pacific oyster, Crassostrea gigas (CgVDAC2). The full length of CgVDAC2 was 1,738 bp with an open reading frame of 843 bp that encoded a protein of 281 amino acids. A four-element eukaryotic porin signature motif, a conserved ATP binding motif, and a VKAKV-like sequence were identified in the predicted CgVDAC2. Expression pattern analysis in different tissues and developmental stages as well as upon infection by ostreid herpesvirus 1 revealed the energy supply-related and immunity-related expression of CgVDAC2. CgVDAC2 was co-localized with mitochondria when it was transiently transfected into HeLa cells. Overexpression of CgVDAC2 in HEK293T cells suppressed the UV irradiation-induced apoptosis by inhibiting the pro-apoptotic function of CgBak. RNA interference induced reduction in CgVDAC2 expression showed a promoted apoptosis level upon UV light irradiation in hemocytes. The yeast two-hybrid system and co-immunoprecipitation assay indicated a direct interaction between CgVDAC2 and the pro-apoptotic protein CgBak. This study revealed the function of VDAC2 in oyster and provided new insights into its involvement in apoptosis modulation and host defense in mollusks. PMID:26727366

  15. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

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    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  16. A novel lipopeptide from skin commensal activates TLR2/CD36-p38 MAPK signaling to increase antibacterial defense against bacterial infection.

    Directory of Open Access Journals (Sweden)

    Dongqing Li

    Full Text Available Staphylococcus epidermidis (S.epidermidis plays important protective roles by directly producing or by stimulating hosts to produce antimicrobial peptides (AMPs against pathogenic infections. Although several AMPs from S.epidermidis have been identified, molecules that stimulate hosts to produce AMPs remain largly unknown. Here we demonstrate that a new lipopeptide (named LP01 purified from S.epidermidis culture media has a unique structure with heneicosanoic acid (21 carbons binding to lysine(11 of a peptide chain. In vitro LP01 increased the expression of β-defensin 2(hBD2 and hBD3 in neonatal human epidermal keratinocytes(NHEK, leading to increased capacity of cell lysates to inhibit the growth of S.aureus. In vivo LP01 induced the expression of mouse β-defensin 4(mBD4 to decrease the survival of local S.aureus in skin and systemic S.aureus survival in liver. The induction of beta-defensins by LP01 was dependent on TLR2 as Tlr2-deficient mice had decreased mBD4. Furthermore, knockdown of CD36 decreased the expression of hBD2 and hBD3, and p38 MAPK inhibitor significantly inhibited the expression of hBDs induced by LP01.Taken together, these findings demonstrate that lipopeptide LP01 from normal commensal S.epidermidis increases antimicrobial peptide hBD2 and hBD3 expression via the activation of TLR2/CD36-p38 MAPK, thus enhancing antimicrobial defense against pathogenic infections.

  17. Roles of MAS-related G protein coupled receptor-X2 (MRGPRX2) on mast cell-mediated host defense, pseudoallergic drug reactions and chronic inflammatory diseases

    Science.gov (United States)

    Subramanian, Hariharan; Gupta, Kshitij; Ali, Hydar

    2016-01-01

    Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders. PMID:27448446

  18. Peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog Xenopus ruwenzoriensis (Pipidae).

    Science.gov (United States)

    Coquet, Laurent; Kolodziejek, Jolanta; Jouenne, Thierry; Nowotny, Norbert; King, Jay D; Conlon, J Michael

    2016-09-01

    The Uganda clawed frog Xenopus ruwenzoriensis with a karyotype of 2n=108 is one of the very few vertebrates with dodecaploid status. Peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 6 peptides), xenopsin precursor fragment (XPF; 3 peptides), caerulein precursor fragment (CPF; 8 peptides), and caerulein precursor fragment-related peptide (CPF-RP; 3 peptides). In addition, the secretions contained caerulein, identical to the peptide from Xenopus laevis, and two peptides that were identified as members of the trefoil factor family (TFF). The data indicate that silencing of the host-defense peptide genes following polyploidization has been appreciable and non-uniform. Consistent with data derived from comparison of nucleotide sequences of mitochrondrial and nuclear genes, cladistic analyses based upon the primary structures of the host-defense peptides provide support for an evolutionary scenario in which X. ruwenzoriensis arose from an allopolyploidization event involving an octoploid ancestor of the present-day frogs belonging to the Xenopus amieti species group and a tetraploid ancestor of Xenopus pygmaeus. PMID:27290612

  19. Survival to parasitoids in an insect hosting defensive symbionts: a multivariate approach to polymorphic traits affecting host use by its natural enemy.

    Directory of Open Access Journals (Sweden)

    Emilie Bilodeau

    Full Text Available Insect parasitoids and their insect hosts represent a wide range of parasitic trophic relations that can be used to understand the evolution of biotic diversity on earth. Testing theories of coevolution between hosts and parasites is based on factors directly involved in host susceptibility and parasitoid virulence. We used controlled encounters with potential hosts of the Aphidius ervi wasp to elucidate behavioral and other phenotypic traits of host Acyrthosiphon pisum that most contribute to success or failure of parasitism. The host aphid is at an advanced stage of specialization on different crop plants, and exhibits intra-population polymorphism for traits of parasitoid avoidance and resistance based on clonal variation of color morph and anti-parasitoid bacterial symbionts. Randomly selected aphid clones from alfalfa and clover were matched in 5 minute encounters with wasps of two parasitoid lineages deriving from hosts of each plant biotype in a replicated transplant experimental design. In addition to crop plant affiliation (alfalfa, clover, aphid clones were characterized for color morph (green, pink, Hamiltonella defensa and Regiella insecticola symbionts, and frequently used behaviors in encounters with A. ervi wasps. A total of 12 explanatory variables were examined using redundancy analysis (RDA to predict host survival or failure to A. ervi parasitism. Aphid color was the best univariate predictor, but was poorly predictive in the RDA model. In contrast, aphid host plant and symbionts were not significant univariate predictors, but significant predictors in the multivariate model. Aphid susceptibility to wasp acceptance as reflected in host attacks and oviposition clearly differed from its suitability to parasitism and progeny development. Parasitoid progeny were three times more likely to survive on clover than alfalfa host aphids, which was compensated by behaviorally adjusting eggs invested per host. Strong variation of the

  20. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

    Directory of Open Access Journals (Sweden)

    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

  1. The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents

    Directory of Open Access Journals (Sweden)

    Michael G. Morash

    2011-09-01

    The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of action. Cytotoxicities were assessed in vitro using cell-based assays and in vivo using zebrafish embryos. Morphological changes were assessed by both transmission and scanning electron microscopy, and functional assays were performed on zebrafish embryos to investigate the mechanism of cell death. A total of 14 peptides were virtually inactive against HL60 human leukemia cells, whereas 12 caused >50% death at ≤32 μg/ml. Morphological changes characteristic of oncosis were evident by electron microscopy after only 1 minute of treatment with 32 μg/ml of variant NRC-03. Only two peptides were hemolytic. Four peptides showed no toxicity towards zebrafish embryos at the highest concentration tested (25 μM; ∼64 μg/ml and one peptide was highly toxic, killing 4-hour-post-fertilization (hpf embryos immediately after exposure to 1 μM peptide. Four other peptides killed embryos after 24 hours of exposure at 1 μM. Most peptides caused mortality at one or more developmental stages only after continuous exposure (24 hours with higher lethal doses (≥5 μM. Pleurocidin NRC-03 bound to embryos and induced the release of superoxide, caused an increase in the number of TUNEL-positive nuclei, and caused membrane damage and the loss of embryonic epithelial integrity, marked by the exclusion of cells from the outer epithelium and the appearance of F-actin within the circumferential cells of the repair site. Our results indicate that specific pleurocidin variants are attractive cancer-selective agents

  2. Purification and Characterization of an Antibacterial Protein from the Cultured Mycelia of Cordyceps sinensis

    Institute of Scientific and Technical Information of China (English)

    HU Zheng; YE Maoqing; XIA Liqiu; TU Wenjuan; LI Liang; ZOU Guolin

    2006-01-01

    An antibacterial protein was isolated from the cultured mycelia of Cordyceps sinensis, and was designated as Cordyceps sinensis Antibacterial Protein (CSAP). CSAP was single-chained, with an apparent molecular mass of 35 × 103 revealed by SDS-PAGE and a novel hydrophobic N-terminal sequence N-ALATQHGAP. The antimicrobial assays showed CSAP could inhibit the growth of Gram-positive and Gram-negative bacteria but no significant inhibition against fungi or yeasts. Furthermore, the antibacterial activity of CSAP was not bactericidal but bacteriostatic. It was the first time that an antibacterial protein was described in the Cordyceps species, which might involve in the chemical defense mechanism of the hosts.

  3. RpkA, a highly conserved GPCR with a lipid kinase domain, has a role in phagocytosis and anti-bacterial defense.

    Directory of Open Access Journals (Sweden)

    Tanja Y Riyahi

    Full Text Available RpkA (Receptor phosphatidylinositol kinase A is an unusual seven-helix transmembrane protein of Dictyostelium discoideum with a G protein coupled receptor (GPCR signature and a C-terminal lipid kinase domain (GPCR-PIPK predicted as a phosphatidylinositol-4-phosphate 5-kinase. RpkA-homologs are present in all so far sequenced Dictyostelidae as well as in several other lower eukaryotes like the oomycete Phytophthora, and in the Legionella host Acanthamoeba castellani. Here we show by immunofluorescence that RpkA localizes to endosomal membranes and is specifically recruited to phagosomes. RpkA interacts with the phagosomal protein complex V-ATPase as proteins of this complex co-precipitate with RpkA-GFP as well as with the GST-tagged PIPK domain of RpkA. Loss of RpkA leads to a defect in phagocytosis as measured by yeast particle uptake. The uptake of the pathogenic bacterium Legionella pneumophila was however unaltered whereas its intra-cellular replication was significantly enhanced in rpkA(-. The difference between wild type and rpkA(- was even more prominent when L. hackeliae was used. When we investigated the reason for the enhanced susceptibility for L. pneumophila of rpkA(- we could not detect a difference in endosomal pH but rpkA(- showed depletion of phosphoinositides (PIP and PIP(2 when we compared metabolically labeled phosphoinositides from wild type and rpkA(-. Furthermore rpkA(- exhibited reduced nitrogen starvation tolerance, an indicator for a reduced autophagy rate. Our results indicate that RpkA is a component of the defense system of D. discoideum as well as other lower eukaryotes.

  4. Relationships among CFTR expression, HCO3− secretion, and host defense may inform gene- and cell-based cystic fibrosis therapies

    Science.gov (United States)

    Shah, Viral S.; Ernst, Sarah; Tang, Xiao Xiao; Karp, Philip H.; Parker, Connor P.; Ostedgaard, Lynda S.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Airway disease is the major source of morbidity and mortality. Successful implementation of gene- and cell-based therapies for CF airway disease requires knowledge of relationships among percentages of targeted cells, levels of CFTR expression, correction of electrolyte transport, and rescue of host defense defects. Previous studies suggested that, when ∼10–50% of airway epithelial cells expressed CFTR, they generated nearly wild-type levels of Cl− secretion; overexpressing CFTR offered no advantage compared with endogenous expression levels. However, recent discoveries focused attention on CFTR-mediated HCO3− secretion and airway surface liquid (ASL) pH as critical for host defense and CF pathogenesis. Therefore, we generated porcine airway epithelia with varying ratios of CF and wild-type cells. Epithelia with a 50:50 mix secreted HCO3− at half the rate of wild-type epithelia. Likewise, heterozygous epithelia (CFTR+/− or CFTR+/∆F508) expressed CFTR and secreted HCO3− at ∼50% of wild-type values. ASL pH, antimicrobial activity, and viscosity showed similar relationships to the amount of CFTR. Overexpressing CFTR increased HCO3− secretion to rates greater than wild type, but ASL pH did not exceed wild-type values. Thus, in contrast to Cl− secretion, the amount of CFTR is rate-limiting for HCO3− secretion and for correcting host defense abnormalities. In addition, overexpressing CFTR might produce a greater benefit than expressing CFTR at wild-type levels when targeting small fractions of cells. These findings may also explain the risk of airway disease in CF carriers. PMID:27114540

  5. Secreted effectors of the tomato leaf mould fungus Cladosporium fulvum are virulence factors that target host defense

    Science.gov (United States)

    Cladosporium fulvum is a biotrophic fungal pathogen that causes leaf mould of tomato. Inside the leaf, C. fulvum does not penetrate host cells or develop haustoria but remains confined to the intercellular space between mesophyll cells. Ten effector proteins that are secreted during host colonizatio...

  6. Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts.

    OpenAIRE

    Chignard, Michel; Balloy, Viviane; Sallenave, Jean-Michel; Si-Tahar, Mustapha

    2007-01-01

    Toll-like receptors are key to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence shows that defects in Toll-like receptors or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection, including aspergillosis. Patients receiving an immunosuppressive regimen, including corticosteroid therapy or cytotoxic chemotherapy, are also susceptible to infections. Aspergillus ...

  7. Chlamydia psittaci: new insights into genomic diversity, clinical pathology, host-pathogen interaction and anti-bacterial immunity.

    Science.gov (United States)

    Knittler, Michael R; Berndt, Angela; Böcker, Selina; Dutow, Pavel; Hänel, Frank; Heuer, Dagmar; Kägebein, Danny; Klos, Andreas; Koch, Sophia; Liebler-Tenorio, Elisabeth; Ostermann, Carola; Reinhold, Petra; Saluz, Hans Peter; Schöfl, Gerhard; Sehnert, Philipp; Sachse, Konrad

    2014-10-01

    The distinctive and unique features of the avian and mammalian zoonotic pathogen Chlamydia (C.) psittaci include the fulminant course of clinical disease, the remarkably wide host range and the high proportion of latent infections that are not leading to overt disease. Current knowledge on associated diseases is rather poor, even in comparison to other chlamydial agents. In the present paper, we explain and summarize the major findings of a national research network that focused on the elucidation of host-pathogen interactions in vitro and in animal models of C. psittaci infection, with the objective of improving our understanding of genomics, pathology, pathophysiology, molecular pathogenesis and immunology, and conceiving new approaches to therapy. We discuss new findings on comparative genome analysis, the complexity of pathophysiological interactions and systemic consequences, local immune response, the role of the complement system and antigen presentation pathways in the general context of state-of-the-art knowledge on chlamydial infections in humans and animals and single out relevant research topics to fill remaining knowledge gaps on this important yet somewhat neglected pathogen.

  8. Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromized hosts.

    Science.gov (United States)

    Chignard, Michel; Balloy, Viviane; Sallenave, Jean-Michel; Si-Tahar, Mustapha

    2007-09-01

    Toll-like receptors are key to pathogen recognition by a host and to the subsequent triggering of an innate immune response. Experimental and clinical evidence shows that defects in Toll-like receptors or in signaling pathways downstream from these receptors render hosts susceptible to various types of infection, including aspergillosis. Patients receiving an immunosuppressive regimen, including corticosteroid therapy or cytotoxic chemotherapy, are also susceptible to infections. Aspergillus fumigatus is an opportunistic pathogen that infects the lungs of immunosuppressed hosts. Here, we review the evidence that experimental inactivation of various Toll-like receptors and of their signaling pathways may worsen cases of invasive pulmonary aspergillosis. Moreover, the literature clearly indicates that the type of immunosuppression is very important, as it influences whether or not Toll-like receptors contribute to infection. The involvement of Toll-like receptors, based on the immunological status of the patient, should be considered if an immunosuppressive treatment must be administered. PMID:17604224

  9. S100A8/A9 Is Not Involved in Host Defense against Murine Urinary Tract Infection

    NARCIS (Netherlands)

    M.C. Dessing; L.M. Butter; G.J. Teske; N. Claessen; C.M. van der Loos; T. Vogl; J. Roth; T. van der Poll; S. Florquin; J.C. Leemans

    2010-01-01

    Background: Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs) that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes indu

  10. DNA vaccination based on pyolysin co-immunized with IL-1β enhances host antibacterial immunity against Trueperella pyogenes infection.

    Science.gov (United States)

    Huang, Ting; Zhao, Kelei; Zhang, Ziqi; Tang, Ce; Zhang, Xiuyue; Yue, Bisong

    2016-06-24

    Trueperella pyogenes is a commensal and opportunistic pathogen normally causes mastitis, liver abscesses and pneumonia of economically important livestock. To date, no specific control measure was reported to prevent T. pyogenes infections. In this study, we first constructed a recombinant plasmid pVAX1-PLO based on the main virulent factor pyolysin gene as DNA vaccine against T. pyogenes infection. Subsequently, transient expression of pVAX1-PLO and pcDNA3.1/V5-fIL-1β were identified in Human embryonic kidney cells (HEK293T) by immunofluorescence assay. Humoral and cellular immune responses were evaluated in mice to compare the immunogenicity between different immunized groups. The results showed that the successful expression of PLO or fIL-1β protein was detected by confocal microscopy for cells transfected with plasmid pVAX1-PLO and/or pcDNA3.1/V5-fIL-1β. The mice immunized with pVAX1-PLO elicited a higher titer of PLO-specific antibody than the control group. The levels of IFN-γ and IL-2 were significantly increased in the pVAX1-PLO immunized mice, while the expression level of IL-4 was slightly increased but not significant. These findings suggested that the DNA vaccine pVAX1-PLO can primarily induce Th1 immune response. The residual Colony-Forming Units (CFUs) from the liver and peritoneal fluid were decreased obviously in the pVAX1-PLO treated mice compared with the control. Importantly, co-immunization with pcDNA3.1/V5-fIL-1β and pVAX1-PLO could enhance host humoral and cellular immune responses and significantly protect mouse from T. pyogenes infection. In conclusion, our study provides a promising strategy against T. pyogenes infections and implies the potential clinical application of combined DNA vaccines in diseases control. PMID:27091688

  11. Antibacterial textiles

    OpenAIRE

    Bhaskara, Usha Rashmi

    2015-01-01

    The aim of this thesis was the antibacterial functionalization of textiles and its application in professional laundries. The antibacterial functionalization was meant for the various textile packages lent out by the laundry companies to their customers from hotels, hospital or food industries. The work in this thesis proposed the antibacterial functionalization of the textile during the laundering process in contrast to the standard washing step. An antibacterial functionalization of the tex...

  12. Cement-based radioactive waste hosts formed under elevated temperatures and pressures (FUETAP concretes) for Savannah River Plant high-level defense waste

    International Nuclear Information System (INIS)

    Concretes that are formed under elevated temperatures and pressures (called FUETAP) are effective hosts for high-level radioactive defense wastes. Tailored concretes developed at the Oak Ridge National Laboratory (ORNL) have been prepared from common Portland cements, fly ash, sand, clays, and waste products. These concretes are produced by accelerated curing under mild autoclave conditions (85 to 2000C, 0.1 to 1.5 MPa) for 24 h. The solids are subsequently dewatered (to remove unbound water) at 2500C for 24 h. The resulting products are strong (compressive strength, 40 to 100 MPa), leach resistant [plutonium leaches at the rate of 10 pg/(cm2.d)], and radiolytically stable, monolithic waste forms (total gas value = 0.005 molecule/100 eV). This report summarizes the results of a 4-year FUETAP development program for Savannah River Plant (SRP) high-level defense wastes. It addresses the major questions concerning the performance of concretes as radioactive waste forms. These include leachability, radiation stability, thermal stability, thermal conductivity, impact strength, permeability, phase complexity, and effect of waste composition

  13. Herbal Antibacterials: A Review

    OpenAIRE

    Chirag Modi; Shailesh Mody; Hitesh Patel; Ghanshyam Dudhatra; Avinash Kumar; Madhavi Awale

    2012-01-01

    Plants are rich source of antibacterial agents because they produce wide array of bioactive molecules, most of which probably evolved as chemical defense against predation or infection. A major part of the total population in developing countries still uses traditional folk medicine obtained from plant resources With an estimation of WHO that as many as 80% of world population living in rural areas rely on herbal traditional medicines as their primary health care, the study on properties and...

  14. S100A8/A9 is not involved in host defense against murine urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Mark C Dessing

    Full Text Available BACKGROUND: Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes induce an inflammatory response and their expression correlates with disease severity in several inflammatory disorders. S100A8/A9 promote endotoxin- and Escherichia (E. coli-induced sepsis showing its contribution in systemic infection. The role of S100A8/A9 during a local infection of the urinary tract system caused by E. coli remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the contribution of S100A8/A9 in acute urinary tract infection (UTI by instilling 2 different doses of uropathogenic E. coli transurethrally in wild type (WT and S100A9 knockout (KO mice. Subsequently, we determined bacterial outgrowth, neutrophilic infiltrate and inflammatory mediators in bladder and kidney 24 and 48 hours later. UTI resulted in a substantial increase of S100A8/A9 protein in bladder and kidney tissue of WT mice. S100A9 KO mice displayed similar bacterial load in bladder or kidney homogenate compared to WT mice using 2 different doses at 2 different time points. S100A9 deficiency had little effect on the inflammatory responses to E. Coli-induced UTI infection, as assessed by myeloperoxidase activity in bladder and kidneys, histopathologic analysis, and renal and bladder cytokine concentrations. CONCLUSIONS: We show that despite high S100A8/A9 expression in bladder and kidney tissue upon UTI, S100A8/A9 does not contribute to an effective host response against E. Coli in the urinary tract system.

  15. Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

    Science.gov (United States)

    Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

    2014-01-01

    The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

  16. Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis.

    Science.gov (United States)

    Böttcher, Tobias; Spreer, Annette; Azeh, Ivo; Nau, Roland; Gerber, Joachim

    2003-03-01

    Matrix metalloproteinase-9 (MMP-9) appears to contribute to blood-brain barrier damage and neuronal injury in bacterial meningitis. To further explore the function of MMP-9 in meningeal inflammation, we injected 10(4) colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9(-/-), n=16) and wild-type controls (129 x B6, n=15). The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ. Yet, clearance of the bacteria from blood (log CFU/ml 4.7 [3.8/5.4] vs. 3.6 [3.0/4.0]; P=0.005) and spleen homogenates (log CFU/ml 5.3 [4.8/5.5] vs. 4.0 [2.8/4.7]; P=0.01) was reduced in MMP-9 deficient mice. A reduced systemic bacterial clearance of MMP-9(-/-) mice was confirmed in experimental S. pneumoniae peritonitis/sepsis. This implies a compromised systemic, but not intracerebral host response against S. pneumoniae in MMP-9 deficiency. PMID:12581831

  17. Antibacterial textiles

    NARCIS (Netherlands)

    Bhaskara, Usha Rashmi

    2015-01-01

    The aim of this thesis was the antibacterial functionalization of textiles and its application in professional laundries. The antibacterial functionalization was meant for the various textile packages lent out by the laundry companies to their customers from hotels, hospital or food industries. The

  18. Host-defense peptides from skin secretions of Fraser's clawed frog Xenopus fraseri (Pipidae): Further insight into the evolutionary history of the Xenopodinae.

    Science.gov (United States)

    Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Nowotny, Norbert; Coquet, Laurent; Leprince, Jérôme; Jouenne, Thierry; Vaudry, Hubert

    2014-12-01

    Peptidomic analysis of norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus fraseri Boulenger, 1905 (Pipidae) led to identification of 13 host-defense peptides. The primary structures of the peptides demonstrate that they belong to the magainin (3 peptides), peptide glycine-leucine-amide, PGLa (4 peptides), and xenopsin-precursor fragment, XPF (2 peptides) families, first identified in Xenopus laevis, together with caerulein precursor fragment-related peptides, CPF-RP (4 peptides), first identified in Silurana tropicalis. In addition, the secretions contain a molecular variant of xenopsin displaying the substitution Arg(4)→Lys compared with X. laevis xenopsin and peptide glycine-tyrosine-amide (PGYa) (GRIIPIYPEFERVFA KKVYPLY.NH2) whose function is unknown. The most potent antimicrobial peptide identified is CPF-RP-F1 (GFGSVLGKALKFGANLL.NH2) with MIC=12.5μM against Staphylococcus aureus and 50μM against Escherichia coli. On the basis of similarities in morphology and advertisement calls, X. fraseri has been placed in a species group that includes the octoploids Xenopus amieti and Xenopus andrei, and the tetraploid Xenopus pygmaeus. Cladistic analyses based upon the primary structures of magainin, PGLa, and CPF-RP peptides support a close evolutionary relationship between X. fraseri, X. amieti and X. andrei but suggest a more distant relationship with X. pygmaeus. PMID:25463057

  19. A MyD88-dependent IFNγR-CCR2 signaling circuit is required for mobilization of monocytes and host defense against systemic bacterial challenge

    Institute of Scientific and Technical Information of China (English)

    Eric M Pietras; Lloyd S Miller; Carl T Johnson; Ryan M O'Connell; Paul W Dempsey; Genhong Cheng

    2011-01-01

    Monocytes are mobilized to sites of infection via interaction between the chemokine MCP-1 and its receptor, CCR2, at which point they differentiate into macrophages that mediate potent antimicrobial effects. In this study, we investigated the mechanisms by which monocytes are mobilized in response to systemic challenge with the intracellular bacterium Francisella tularensis. We found that mice deficient in MyD88, interferon-γ (IFNγ)R or CCR2 all had defects in the expansion of splenic monocyte populations upon F. tularensis challenge, and in control of F. tularensis infection. Interestingly, MyD88-deficient mice were defective in production of IFNγ, and IFNγR deficient mice exhibited defective production of MCP-1, the ligand for CCR2. Transplantation of IFNγR-deficient bone marrow (BM) into wild-type mice further suggested that mobilization of monocytes in response to F. tularensis challenge required IFNγR expression on BM-derived cells. These studies define a critical host defense circuit wherein MyD88-dependent IFNγ production signals via IFNγR expressed on BM-derived cells, resulting in MCP-1 production and activation of CCR2-dependent mobilization of monocytes in the innate immune response to systemic F. tularensis challenge.

  20. Leaf-mining by Phyllonorycter blancardella reprograms the host-leaf transcriptome to modulate phytohormones associated with nutrient mobilization and plant defense.

    Science.gov (United States)

    Zhang, Hui; Dugé de Bernonville, Thomas; Body, Mélanie; Glevarec, Gaëlle; Reichelt, Michael; Unsicker, Sybille; Bruneau, Maryline; Renou, Jean-Pierre; Huguet, Elisabeth; Dubreuil, Géraldine; Giron, David

    2016-01-01

    Phytohormones have long been hypothesized to play a key role in the interactions between plant-manipulating organisms and their host-plants such as insect-plant interactions that lead to gall or 'green-islands' induction. However, mechanistic understanding of how phytohormones operate in these plant reconfigurations is lacking due to limited information on the molecular and biochemical phytohormonal modulation following attack by plant-manipulating insects. In an attempt to fill this gap, the present study provides an extensive characterization of how the leaf-miner Phyllonorycter blancardella modulates the major phytohormones and the transcriptional activity of plant cells in leaves of Malus domestica. We show here, that cytokinins strongly accumulate in mined tissues despite a weak expression of plant cytokinin-related genes. Leaf-mining is also associated with enhanced biosynthesis of jasmonic acid precursors but not the active form, a weak alteration of the salicylic acid pathway and a clear inhibition of the abscisic acid pathway. Our study consolidates previous results suggesting that insects may produce and deliver cytokinins to the plant as a strategy to manipulate the physiology of the leaf to create a favorable nutritional environment. We also demonstrate that leaf-mining by P. blancardella leads to a strong reprogramming of the plant phytohormonal balance associated with increased nutrient mobilization, inhibition of leaf senescence and mitigation of plant direct and indirect defense.

  1. Herbal Antibacterials: A Review

    Directory of Open Access Journals (Sweden)

    Chirag Modi

    2012-02-01

    Full Text Available Plants are rich source of antibacterial agents because they produce wide array of bioactive molecules, most of which probably evolved as chemical defense against predation or infection. A major part of the total population in developing countries still uses traditional folk medicine obtained from plant resources With an estimation of WHO that as many as 80% of world population living in rural areas rely on herbal traditional medicines as their primary health care, the study on properties and uses of medicinal plants are getting growing interests. In recent years this interest to evaluate plants possessing antibacterial activity for various diseases is growing. Different solvent extracts (aqueous, alcohol and ethanol of leaves, flower and seed of various plants selected based on an ethnobotanical survey from India were subjected to in vitro antibacterial activity assay against Gram-positive and Gram-negative bacteria employing different diffusion method. Based on local use of common diseases and Ethnobotanical knowledge, an attempt has been made to assess the antibacterial properties of selected medicinal plants viz. Argemone mexicana (Shialkanta, Aster lanceolatus (White panicle, Capparis thonningii and Capparis tomentosa (Woolly caper bush, Cardiospermum halicacabum (Balloonvine, Cassia alata (Herpetic alata, Centaurea sclerolepis, Cinnamomum zeylanicum (Cinnamon, Curcuma longa (Turmeric, Cymbopogon nervatus, Ficus religiosa (Peepal, Indigofera aspalathoides (Ajara, Marrubium vulgare (Horehound, Medicago Spp.(Medick, Burclover, Morus alba (Mulberry, Ocimum sanctum (Tulsi, Origanum marjorana (Marjoram, Oxalis corniculata (Amli, Piper nigrum (Kala mirch, Plectranthus amboinicus (Indian borage, Patharchur, Plumeria acutifolia (Kachuchi, Salvadora persica (Piludi, Salvia repens and Syzygium aromaticum (Clove for potential antibacterial activity against some important bacterial strains, namely Bacillus subtilis, Bacillus cereus, Staphylococcus

  2. Synergistic interaction among begomoviruses leads to the suppression of host defense-related gene expression and breakdown of resistance in chilli.

    Science.gov (United States)

    Singh, Ashish Kumar; Kushwaha, Nirbhay; Chakraborty, Supriya

    2016-05-01

    Chilli (Capsicum sp.) is one of the economically important spice and vegetable crops grown in India and suffers great losses due to the infection of begomoviruses. Conventional breeding approaches have resulted in development of a few cultivars of chilli resistant to begomoviruses. A severe leaf curl disease was observed on one such resistant chilli cultivar (Capsicum annuum cv. Kalyanpur Chanchal) grown in the experimental field of the Jawaharlal Nehru University, New Delhi. Four different viral genomic components namely, Chilli leaf curl virus (DNA A), Tomato leaf curl Bangladesh betasatellite (DNA β), Tomato leaf curl New Delhi virus (DNA A), and Tomato leaf curl Gujarat virus (DNA B) were associated with the severe leaf curl disease. Further, frequent association of these four genomic components was also observed in symptomatic plants of other chilli cultivars (Capsicum annuum cv. Kashi Anmol and Capsicum chinense cv. Bhut Jolokia) grown in the experimental field. Interaction studies among the isolated viral components revealed that Nicotiana benthamiana and chilli plants inoculated with four genomic components of begomoviruses exhibited severe leaf curl disease symptoms. In addition, this synergistic interaction resulted in increased viral DNA accumulation in infected plants. Resistant chilli plants co-inoculated with four genomic components of begomoviruses showed drastic reduction of host basal (ascorbate peroxidase, thionin, polyphenol oxidase) and specific defense-related gene (NBS-LRR) expression. Our results suggested that synergistic interaction among begomoviruses created permissive cellular environment in the resistant chilli plants which leads to breakdown of natural resistance, a phenomenon observed for the first time in chilli. PMID:26780359

  3. A teleostan homolog of catalase from black rockfish (Sebastes schlegelii): insights into functional roles in host antioxidant defense and expressional responses to septic conditions.

    Science.gov (United States)

    Elvitigala, Don Anushka Sandaruwan; Priyathilaka, Thanthrige Thiunuwan; Whang, Ilson; Nam, Bo-Hye; Lee, Jehee

    2015-05-01

    Antioxidative defense renders a significant protection against environmental stress in organisms and maintains the correct redox balance in cells, thereby supporting proper immune function. Catalase is an indispensable antioxidant in organisms that detoxifies hydrogen peroxides produced in cellular environments. In this study, we sought to molecularly characterize a homolog of catalase (RfCat), identified from black rockfish (Sebastes schlegelii). RfCat consists of a 1581 bp coding region for a protein of 527 amino acids, with a predicted molecular weight of 60 kD. The protein sequence of RfCat harbored similar domain architecture to known catalases, containing a proximal active site signature and proximal heme ligand signature, and further sharing prominent homology with its teleostan counterparts. As affirmed by multiple sequence alignments, most of the functionally important residues were well conserved in RfCat. Furthermore, our phylogenetic analysis indicates its common vertebrate ancestral origin and a close evolutionary relationship with teleostan catalases. Recombinantly expressed RfCat demonstrated prominent peroxidase activity that varied with different substrate and protein concentrations, and protected against DNA damage. RfCat mRNA was ubiquitously expressed among different tissues examined, as detected by qPCR. In addition, RfCat mRNA expression was modulated in response to pathogenic stress elicited by Streptococcus iniae and poly I:C in blood and spleen tissues. Collectively, our findings indicate that RfCat may play an indispensable role in host response to oxidative stress and maintain a correct redox balance after a pathogen invasion.

  4. Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease.

    Directory of Open Access Journals (Sweden)

    Lori R Shapiro

    Full Text Available Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV. We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host

  5. Protein and lipid interactions of mammalian antibacterial peptides

    OpenAIRE

    Wang, Yuqin

    2001-01-01

    Gene-encoded antibacterial peptides are multifunctional effector molecules and play an important role in host innate immunity. Upon stimulation, the mature active peptides are released from inactive precursors. Cathelicidins constitute a family of antibacterial peptides, which share a conserved N-terminal cathelin-like region followed by a variable C-terminal antibacterial domain. In addition to its antibacterial activity, LL-37, the only cathelicidin found in human, is ...

  6. The Effect of Water Limitation on Volatile Emission, Tree Defense Response, and Brood Success of Dendroctonus ponderosae in Two Pine Hosts, Lodgepole, and Jack Pine

    OpenAIRE

    Lusebrink, Inka; Erbilgin, Nadir; Evenden, Maya L.

    2016-01-01

    The mountain pine beetle (MPB; Dendroctonus ponderosae) has recently expanded its range from lodgepole pine forest into the lodgepole × jack pine hybrid zone in central Alberta, within which it has attacked pure jack pine. This study tested the effects of water limitation on tree defense response of mature lodgepole and jack pine (Pinus contorta and Pinus banksiana) trees in the field. Tree defense response was initiated by inoculation of trees with the MPB-associated fungus Grosmannia clavig...

  7. Dynamic defense workshop :

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.

    2013-02-01

    On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-art work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.

  8. Immune defense in leaf-cutting ants: a cross-fostering approach.

    Science.gov (United States)

    Armitage, Sophie A O; Broch, Jens F; Marín, Hermogenes Fernández; Nash, David R; Boomsma, Jacobus J

    2011-06-01

    To ameliorate the impact of disease, social insects combine individual innate immune defenses with collective social defenses. This implies that there are different levels of selection acting on investment in immunity, each with their own trade-offs. We present the results of a cross-fostering experiment designed to address the influences of genotype and social rearing environment upon individual and social immune defenses. We used a multiply mating leaf-cutting ant, enabling us to test for patriline effects within a colony, as well as cross-colony matriline effects. The worker's father influenced both individual innate immunity (constitutive antibacterial activity) and the size of the metapleural gland, which secretes antimicrobial compounds and functions in individual and social defense, indicating multiple mating could have important consequences for both defense types. However, the primarily social defense, a Pseudonocardia bacteria that helps to control pathogens in the ants' fungus garden, showed a significant colony of origin by rearing environment interaction, whereby ants that acquired the bacteria of a foster colony obtained a less abundant cover of bacteria: one explanation for this pattern would be co-adaptation between host colonies and their vertically transmitted mutualist. These results illustrate the complexity of the selection pressures that affect the expression of multilevel immune defenses. PMID:21644963

  9. Antibacterials in Household Products

    Science.gov (United States)

    ... products such as soaps, detergents, health and skincare products and household cleaners. How do antibacterials work? ♦ Antibacterials may be ... contain triclosan or other biocide agents? Antibacterials in household products Are there any risks associated with triclosan-containing ...

  10. Rule based host intrusion defense system research and Implementation%基于规则的主机入侵防御系统的研究与实现

    Institute of Scientific and Technical Information of China (English)

    黄成荣

    2012-01-01

    Host active defense technology is one kind based on single new virus defense technology, by monitoring the process behav- ior, but found the" illegal" behavior, the user is informed, or terminate the process, can achieve the unknown virus prevention. Host intrusion prevention system rule set is the key and difficulty. Starting from the basic rules of structure, rule definition, priority of rules, software restriction strategy and other aspects of host intrusion prevention system of the rule set is studied. And further design and implementation of rule based host intrusion prevention system, experiments show that, the system has a relatively flexible active defence function.%主机主动防御技术就是一种基于单机的新型的病毒防御技术,通过监视进程的行为,一但发现“违规”行为,就通知用户,或者直接终止进程,能够实现对未知病毒的防范。规则设置是主机入侵防御系统的重点和难点。本文从基础规则结构、规则定义、规则优先级、软件限制策略等方面对主机入侵防御系统的规则设置进行了深入研究。并进一步设计实现了基于规则的主机入侵防御系统,实验证明,该系统具有为较为灵活的主动防御功能。

  11. Antibacterial substance from mucus of a scleractinian coral,Symphyllia gigantea

    Institute of Scientific and Technical Information of China (English)

    CHEN Guohua; HUANG Liangmin; TAN Yehui; YIN Jianqiang; WANG Hankui; HUANG Hui; ZOU Kun; LI Ruiping

    2007-01-01

    Coral mucus covers the surface of coral and contains antibacterial substances as a first line of defense. Coral mucus not only enables the coral itself to resist disease, but also provides antibacterial agents for people. We collected mucus from a scleractinian coral (Symphyllia gigantea) at Sta. Sanya (China), then extracted the antibacterial substances using 10% glacial acetic acid with the help of antiprotease inhibitors, and tested the antibacterial activity by a terrestrial bacterium (Staphylococcus aurevs) and a marine bacterium (Vibrio anguillarum). The result showed that, there were antibacterial agents in the mucus, and their antibacterial activities were lost by treatment of the sample at 90 °C water for 10 min.

  12. Neisseria gonorrhoeae modulates iron-limiting innate immune defenses in macrophages.

    Directory of Open Access Journals (Sweden)

    Susu M Zughaier

    Full Text Available Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. The gonococcus can survive extracellularly and intracellularly, but in both environments the bacteria must acquire iron from host proteins for survival. However, upon infection the host uses a defensive response by limiting the bioavailability of iron by a number of mechanisms including the enhanced expression of hepcidin, the master iron-regulating hormone, which reduces iron uptake from the gut and retains iron in macrophages. The host also secretes the antibacterial protein NGAL, which sequesters bacterial siderophores and therefore inhibits bacterial growth. To learn whether intracellular gonococci can subvert this defensive response, we examined expression of host genes that encode proteins involved in modulating levels of intracellular iron. We found that N. gonorrhoeae can survive in association (tightly adherent and intracellular with monocytes and macrophages and upregulates a panel of its iron-responsive genes in this environment. We also found that gonococcal infection of human monocytes or murine macrophages resulted in the upregulation of hepcidin, NGAL, and NRAMP1 as well as downregulation of the expression of the gene encoding the short chain 3-hydroxybutyrate dehydrogenase (BDH2; BDH2 catalyzes the production of the mammalian siderophore 2,5-DHBA involved in chelating and detoxifying iron. Based on these findings, we propose that N. gonorrhoeae can subvert the iron-limiting innate immune defenses to facilitate iron acquisition and intracellular survival.

  13. Antibacterial Targets in Fatty Acid Biosynthesis

    OpenAIRE

    Wright, H. Tonie; Reynolds, Kevin A.

    2007-01-01

    The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs...

  14. 人cathelicidin抗菌肽LL-37在宿主防御系统中的作用%Function of LL-37 in the host defense system

    Institute of Scientific and Technical Information of China (English)

    李方舟; 胡海峰

    2011-01-01

    Cathelicidin is a family of antimicrobial peptides found in mammalian and produced by epithelial cells and LL-37 is the only cathelicidin discoverd in human. As a defensin, LL-37 plays an important role in the human innate immunity. Besides its broad spectrum antibacterial activity, LL-37 possesses additional biological functions including immunomodulatory functions, induction of angiogenesis, neutralination of the lipopolysaccharide, wound repair mechanisms and induction of cells apoptosis. This review describes the expression and distribution of LL-37 as well as its biological feature and mechanism.%存在于哺乳动物中的一类抗菌肽cathelicidin由上皮细胞产生,LL-37为目前在人体内仅发现的一种cathelicidin.同防御素一样,LL-37为人免疫防御系统的重要组成部分,除了具有广谱抗菌活性外,还有免疫调节、诱导血管生成、抗内毒素、促进损伤修复、诱导细胞凋亡等生物学功能.本文综述LL-37的表达分布、生物学活性及其作用机制.

  15. Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1.

    Directory of Open Access Journals (Sweden)

    Erin McElvania Tekippe

    Full Text Available The NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3, its adaptor protein PYCARD (ASC, and caspase-1 during infection with Mycobacterium tuberculosis (Mtb. Mtb infection of macrophages in culture induced IL-1beta secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-, Casp-1(-/-, and WT mice showed no differences in pulmonary IL-1beta production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard(-/- mice. Decreased survival of Pycard(-/- animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.

  16. Francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    Full Text Available Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4. Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways.

  17. IL-17A and Th17 Cells in Lung Inflammation: An Update on the Role of Th17 Cell Differentiation and IL-17R Signaling in Host Defense against Infection

    Directory of Open Access Journals (Sweden)

    Hsing-Chuan Tsai

    2013-01-01

    Full Text Available The significance of Th17 cells and interleukin- (IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Numerous studies have indicated that Th17 cells and its signature cytokine IL-17A are critical to the airway’s immune response against various bacteria and fungal infection. Cytokines such as IL-23, which are involved in Th17 differentiation, play a critical role in controlling Klebsiella pneumonia (K. pneumonia infection. IL-17A acts on nonimmune cells in infected tissues to strengthen innate immunity by inducing the expression of antimicrobial proteins, cytokines, and chemokines. Mice deficient in IL-17 receptor (IL-17R expression are susceptible to infection by various pathogens. In this review, we summarize the recent advances in unraveling the mechanism behind Th17 cell differentiation, IL-17A/IL-17R signaling, and also the importance of IL-17A in pulmonary infection.

  18. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    Science.gov (United States)

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-01

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime.

  19. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: The role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza

    Science.gov (United States)

    Geiss, Gary K.; Salvatore, Mirella; Tumpey, Terrence M.; Carter, Victoria S.; Wang, Xiuyan; Basler, Christopher F.; Taubenberger, Jeffery K.; Bumgarner, Roger E.; Palese, Peter; Katze, Michael G.; García-Sastre, Adolfo

    2002-08-01

    The NS1 protein of influenza A virus contributes to viral pathogenesis, primarily by enabling the virus to disarm the host cell type IFN defense system. We examined the downstream effects of NS1 protein expression during influenza A virus infection on global cellular mRNA levels by measuring expression of over 13,000 cellular genes in response to infection with wild-type and mutant viruses in human lung epithelial cells. Influenza A/PR/8/34 virus infection resulted in a significant induction of genes involved in the IFN pathway. Deletion of the viral NS1 gene increased the number and magnitude of expression of cellular genes implicated in the IFN, NF-B, and other antiviral pathways. Interestingly, different IFN-induced genes showed different sensitivities to NS1-mediated inhibition of their expression. A recombinant virus with a C-terminal deletion in its NS1 gene induced an intermediate cellular mRNA expression pattern between wild-type and NS1 knockout viruses. Most significantly, a virus containing the 1918 pandemic NS1 gene was more efficient at blocking the expression of IFN-regulated genes than its parental influenza A/WSN/33 virus. Taken together, our results suggest that the cellular response to influenza A virus infection in human lung cells is significantly influenced by the sequence of the NS1 gene, demonstrating the importance of the NS1 protein in regulating the host cell response triggered by virus infection.

  20. A cupin domain-containing protein with a quercetinase activity (VdQase regulates Verticillium dahliae’s pathogenicity and contributes to counteracting host defenses

    Directory of Open Access Journals (Sweden)

    Abdel eElHadrami

    2015-06-01

    Full Text Available We previously identified rutin as part of potato root responses to its pathogen Verticillium dahliae. Rutin was directly toxic to the pathogen at doses greater than 160 μM, a threshold below which many V. dahliae pathogenicity-related genes were up-regulated. We identified and characterized a cupin domain-containing protein (VdQase with a dioxygenase activity and a potential role in V. dahliae-potato interactions. The pathogenicity of VdQase knock-out mutants generated through Agrobacterium tumefasciens-mediated transformation was significantly reduced on susceptible potato cultivar Kennebec compared to wild type isolates. Fluorescence microscopy revealed a higher accumulation of flavonols in the stems of infected potatoes and a higher concentration of rutin in the leaves in response to the VdQase mutants as compared to wild type isolates. This, along with the HPLC characterization of high residual and non-utilized quercetin in presence of the knockout mutants, indicates the involvement of VdQase in the catabolism of quercetin and possibly other flavonols in planta. Quantification of Salicylic and Jasmonic Acids (SA, JA in response to the mutants versus wild type isolates revealed involvement of VdQase in the interference with signaling, suggesting a role in pathogenicity. It is hypothesized that the by-product of dioxygenation 2-protocatechuoylphloroglucinolcarboxylic acid, after dissociating into phloroglucinol and protocatechuoyl moieties, becomes a starting point for benzoic acid and SA, thereby interfering with the JA pathway and affecting the interaction outcome. These events may be key factors for V. dahliae in countering potato defenses and becoming notorious in the rhizosphere.

  1. C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection.

    Science.gov (United States)

    Zhu, Le-Le; Zhao, Xue-Qiang; Jiang, Changying; You, Yun; Chen, Xiao-Ping; Jiang, Yuan-Ying; Jia, Xin-Ming; Lin, Xin

    2013-08-22

    C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized α-mannans on the surfaces of C. albicans hyphae and induced NF-κB activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound α-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.

  2. The Importance of the KR-Rich Region of the Coat Protein of Ourmia melon virus for Host Specificity, Tissue Tropism, and Interference With Antiviral Defense.

    Science.gov (United States)

    Rossi, Marika; Vallino, Marta; Abbà, Simona; Ciuffo, Marina; Balestrini, Raffaella; Genre, Andrea; Turina, Massimo

    2015-01-01

    The N-terminal region of the Ourmia melon virus (OuMV) coat protein (CP) contains a short lysine/arginine-rich (KR) region. By alanine scanning mutagenesis, we showed that the KR region influences pathogenicity and virulence of OuMV without altering viral particle assembly. A mutant, called OuMV6710, with three basic residue substitutions in the KR region, was impaired in the ability to maintain the initial systemic infection in Nicotiana benthamiana and to infect both cucumber and melon plants systemically. The integrity of this protein region was also crucial for encapsidation of viral genomic RNA; in fact, certain mutations within the KR region partially compromised the RNA encapsidation efficiency of the CP. In Arabidopsis thaliana Col-0, OuMV6710 was impaired in particle accumulation; however, this phenotype was abolished in dcl2/dcl4 and dcl2/dcl3/dcl4 Arabidopsis mutants defective for antiviral silencing. Moreover, in contrast to CPwt, in situ immunolocalization experiments indicated that CP6710 accumulates efficiently in the spongy mesophyll tissue of infected N. benthamiana and A. thaliana leaves but only occasionally infects palisade tissues. These results provided strong evidence of a crucial role for OuMV CP during viral infection and highlighted the relevance of the KR region in determining tissue tropism, host range, pathogenicity, and RNA affinity, which may be all correlated with a possible CP silencing-suppression activity.

  3. Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.

    Directory of Open Access Journals (Sweden)

    Andrés G Madrigal

    Full Text Available Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1, a mediator of tumor necrosis factor (TNF receptor-1 (TNF-R1-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1, NOD2, Toll-like receptor 2 (TLR2 or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose polymerase (PARP was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders.

  4. Fighting a losing battle: vigorous immune response countered by pathogen suppression of host defenses in the chytridiomycosis-susceptible frog Atelopus zeteki.

    Science.gov (United States)

    Ellison, Amy R; Savage, Anna E; DiRenzo, Grace V; Langhammer, Penny; Lips, Karen R; Zamudio, Kelly R

    2014-07-01

    The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis. We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility complex genes. In addition, fungal-killing genes had significantly greater expression in frogs previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases. However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings, suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus. PMID:24841130

  5. An R2R3 MYB transcription factor in wheat, TaPIMP1, mediates host resistance to Bipolaris sorokiniana and drought stresses through regulation of defense- and stress-related genes.

    Science.gov (United States)

    Zhang, Zengyan; Liu, Xin; Wang, Xindong; Zhou, Miaoping; Zhou, Xianyao; Ye, Xingguo; Wei, Xuening

    2012-12-01

    In this study, we report new insights into the function of a wheat (Triticum aestivum) MYB gene TaPIMP1 through overexpression and underexpression, and its underlying mechanism in wheat. Electrophoretic mobility shift and yeast-one-hybrid assays indicated that TaPIMP1 can bind to five MYB-binding sites including ACI, and activate the expression of the genes with the cis-element, confirming that TaPIMP1 is an MYB transcription activator. TaPIMP1-overexpressing transgenic wheat exhibited significantly enhanced resistance to the fungal pathogen Bipolaris sorokiniana and drought stresses, whereas TaPIMP1-underexpressing transgenic wheat showed more susceptibility to the stresses compared with untransformed wheat, revealing that TaPIMP1 positively modulates host-defense responses to B. sorokiniana and drought stresses. Microarray analysis showed that a subset of defense- and stress-related genes were up-regulated by TaPIMP1. These genes, including TaPIMP1, RD22, TLP4 and PR1a, were regulated by ABA and salicylic acid (SA). TaPIMP1-underexpressing transgenic wheat showed compromised induction of these stress-responsive genes following ABA and SA treatments. In summary, TaPIMP1, as a positive molecular linker, mediates resistance to B. sorokiniana and drought stresses by regulation of stress-related genes in ABA- and SA-signaling pathways in wheat. Furthermore, TaPIMP1 may provide a transgenic tool for engineering multiple-resistance wheat in breeding programs.

  6. Apicomplexan parasites and subversion of the host cell microRNA pathway.

    Science.gov (United States)

    Hakimi, Mohamed-ali; Cannella, Dominique

    2011-11-01

    RNA silencing plays a major role in innate antiviral and antibacterial defenses in plants, insects, and animals through the action of microRNAs (miRNAs). miRNAs can act in favor of the microorganism, either when it is pathogen-encoded or when the microorganism subverts host miRNAs to its benefit. Recent data point to the possibility that apicomplexan parasites have developed tactics to interfere with host miRNA populations in a parasite-specific manner, thereby identifying the RNA-silencing pathway as a new means to reshape their cellular environment. This review highlights the current understanding and new insights concerning the mechanisms that could be involved and the potential roles of the host microRNome (miRNome) in apicomplexan infection.

  7. Antimicrobial peptides in echinoderm host defense.

    Science.gov (United States)

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads. PMID:25445901

  8. Host-Defense Activities of Cyclotides

    Directory of Open Access Journals (Sweden)

    David J. Craik

    2012-02-01

    Full Text Available Cyclotides are plant mini-proteins whose natural function is thought to be to protect plants from pest or pathogens, particularly insect pests. They are approximately 30 amino acids in size and are characterized by a cyclic peptide backbone and a cystine knot arrangement of three conserved disulfide bonds. This article provides an overview of the reported pesticidal or toxic activities of cyclotides, discusses a possible common mechanism of action involving disruption of biological membranes in pest species, and describes methods that can be used to produce cyclotides for potential applications as novel pesticidal agents.

  9. Tobacco smoke. Effects on pulmonary host defense.

    Science.gov (United States)

    Drath, D B; Karnovsky, M L; Huber, G L

    1979-07-01

    Tobacco smoke affected both the metabolism and function of pulmonary alveolar macrophages (PAM). Phagocytosis of viable Staphylococcus aureus and inert starch particles was minimally but consistently depressed in PAM from rats exposed to tobacco smoke for six months. Oxygen consumption, superoxide and hydrogen peroxide release, and hexose monophosphate shunt activity were elevated in cells from smokers. Oxidation of glucose, labelled in the carbon-six position, remained unchanged. All observed effects of tobacco smoke on oxygen metabolism occurred during phagocytosis and did not affect the basal metabolism of the nonstimulated cell. PMID:225267

  10. Antimicrobial peptides in echinoderm host defense.

    Science.gov (United States)

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads.

  11. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  12. 75 FR 40857 - Webinar About Advanced Defense Technologies RFP

    Science.gov (United States)

    2010-07-14

    ... ADMINISTRATION Webinar About Advanced Defense Technologies RFP AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of open webinar meeting to discuss Advanced Defense Technologies (ADT) Request for... webinar it is hosting to answer questions from potential Offerors about the Advanced Defense...

  13. Effect of Exogenous Surfactant Therapy on the Innate Host Defense Systems%外源性PS应用对早产儿先天性免疫系统的影响

    Institute of Scientific and Technical Information of China (English)

    王成祥; 常绍鸿

    2013-01-01

    Objective To investigate the levels of T lymphocytes and NK cells in peripheral blood of preterm infants who were treated with exogenous pulmonary surfactants(exPS). Methods From Jun. 2011 to Jan. 2012, 15 cases of preterm infants who were treated with exPS, selected over the same period 6 cases of full-term healthy infants, peripheral blood T lymphocytes and NK cells were detected and compared. Results The results showed that CD3+, CD4+, NK, and the ratio of CD4+/CD8+ in preterm infants than that in the control group. All of that in post-surfactant were significantly higher than that in pre-surfactant. Conclusion In preterm infants, Treatment with exPS apparently stimulated the innate host defense systems.%  目的研究外源性肺表面活性物质(pulmonary surfactant,PS)的应用对早产儿先天性免疫系统的影响。方法2011年6月-2012年1月于本院住院应用PS治疗的早产儿共15人,测定其应用前、应用后3d血清内外周血T淋巴细胞亚群和NK细胞的活性,并以健康足月儿6名为对照组。结果早产儿应用PS前,血清CD3+、CD4+、NK细胞数量及CD4+/CD8+比值均低于对照组,差异有统计学意义;而CD8+T细胞高于对照组;早产儿应用PS后3天CD3+、CD4+、NK细胞数量及CD4+/CD8+比值均有明显升高,差异有统计学意义;CD8+T细胞减少。结论应用外源性PS可有效提高早产儿先天性免疫系统的功能。

  14. PROPERTIES OF ANTIBACTERIAL MEDICATIONS

    Directory of Open Access Journals (Sweden)

    Boyko N. N.

    2014-01-01

    Full Text Available The possibility to use vector algebra theory for quantitative description of antibacterial medications and comparison of their properties has been shown. Mathematic formulas for description of medications’ antibacterial action basing on data of simple to use well method have been presented. This method allows evaluation of medications’ antibacterial activity and opportunity to choose the most active ones, as well as compare them with each other. It is noted that medications of natural origin are inferior to those of synthetic origin as for their antibacterial activity, and new galenic medications possess the most antimicrobial properties. The prospects of this method for pharmacoeconomic analysis of medications conducted in order to chose optimal cost/quality ratio has been demonstrated.

  15. Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics.

    Directory of Open Access Journals (Sweden)

    Anele Gela

    Full Text Available Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD. There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN, a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI, midkine, human beta defensin-3 (hBD-3, and thymic stromal lymphopoietin (TSLP but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD.

  16. Shedding light on antibacterial activities of cathelicidins

    NARCIS (Netherlands)

    Schneider, V.A.F.

    2016-01-01

    Antibiotic resistance is continuously increasing and has a tremendous impact on human and animal well-being. Attractive alternatives to conventional antibiotics are host defense peptides (HDP), such as chicken cathelicidin-2 (CATH-2) and porcine proline-rich PR-39. HDPs are small cationic molecules

  17. BUTYRATE-MEDIATED GENOMIC CHANGES INVOLVED IN NON-SPECIFIC HOST DEFENSES, MATRIX REMODELING AND THE IMMUNE RESPONSE IN THE RUMEN EPITHELIUM OF COWS AFFLICTED WITH SUBACUTE RUMINAL ACIDOSIS

    Directory of Open Access Journals (Sweden)

    Louis Dionissopoulos

    2013-01-01

    involved in Non-Specific Host Defense (NSHD, Remodeling or adaptation (RM and Immune Response (IR. Of the 49 genes tested by qRT-PCR, 9 (LCN2, MMP1, MUC16, GPX2, CSTA, FUT1, SERPINE2, BCAM, RAC3 were upregulated, 20 (MTOR, AKIRIN2, NFKBIZ, NFKB2, ACVR2A, LAMB1, FRS2, PPARD, LBP, NEDD4L, SGK1, DEDD2, MAP3K8, PARD6B, PLIN2, ADA, HPGD, FMO5, BMP6, TCHH were downregulated and 20 were unchanged due to butyrate administration in the proximal gastrointestinal tract. These results demonstrate the potential protective effect and molecular mechanisms involved in a novel butyrate treatment for inflammatory gastrointestinal conditions.

  18. HostPhinder: A Phage Host Prediction Tool.

    Science.gov (United States)

    Villarroel, Julia; Kleinheinz, Kortine Annina; Jurtz, Vanessa Isabell; Zschach, Henrike; Lund, Ole; Nielsen, Morten; Larsen, Mette Voldby

    2016-01-01

    The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within reach. Here, we present HostPhinder, a tool aimed at predicting the bacterial host of phages by examining the phage genome sequence. Using a reference database of 2196 phages with known hosts, HostPhinder predicts the host species of a query phage as the host of the most genomically similar reference phages. As a measure of genomic similarity the number of co-occurring k-mers (DNA sequences of length k) is used. Using an independent evaluation set, HostPhinder was able to correctly predict host genus and species for 81% and 74% of the phages respectively, giving predictions for more phages than BLAST and significantly outperforming BLAST on phages for which both had predictions. HostPhinder predictions on phage draft genomes from the INTESTI phage cocktail corresponded well with the advertised targets of the cocktail. Our study indicates that for most phages genomic similarity correlates well with related bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2]. PMID:27153081

  19. HostPhinder: A Phage Host Prediction Tool

    Directory of Open Access Journals (Sweden)

    Julia Villarroel

    2016-05-01

    Full Text Available The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within reach. Here, we present HostPhinder, a tool aimed at predicting the bacterial host of phages by examining the phage genome sequence. Using a reference database of 2196 phages with known hosts, HostPhinder predicts the host species of a query phage as the host of the most genomically similar reference phages. As a measure of genomic similarity the number of co-occurring k-mers (DNA sequences of length k is used. Using an independent evaluation set, HostPhinder was able to correctly predict host genus and species for 81% and 74% of the phages respectively, giving predictions for more phages than BLAST and significantly outperforming BLAST on phages for which both had predictions. HostPhinder predictions on phage draft genomes from the INTESTI phage cocktail corresponded well with the advertised targets of the cocktail. Our study indicates that for most phages genomic similarity correlates well with related bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2].

  20. Understanding Defense Mechanisms.

    Science.gov (United States)

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur. PMID:26583439

  1. Recognizing plant defense priming

    NARCIS (Netherlands)

    Martinez-Medina, A.; Flors, V.; Heil, M.; Mauch-Mani, B.; Pieterse, C.M.J.; Pozo, M.J.; Ton, J.; Van Dam, N.M.; Conrath, U.

    2016-01-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in plant

  2. MicroRNA-762 is upregulated in human corneal epithelial cells in response to tear fluid and Pseudomonas aeruginosa antigens and negatively regulates the expression of host defense genes encoding RNase7 and ST2.

    Directory of Open Access Journals (Sweden)

    James Mun

    Full Text Available Mucosal surfaces regulate defenses against infection and excessive inflammation. We previously showed that human tears upregulated epithelial expression of genes encoding RNase7 and ST2, which inhibited Pseudomonas aeruginosa invasion of human corneal epithelial cells. Here, microRNA microarrays were used to show that a combination of tear fluid exposure (16 h then P. aeruginosa antigens (3 h upregulated miR-762 and miR-1207, and down-regulated miR-92 and let-7b (all > 2-fold in human corneal epithelial cells compared to P. aeruginosa antigens alone. RT-PCR confirmed miR-762 upregulation ∼ 3-fold in tear-antigen exposed cells. Without tears or antigens, an antagomir reduced miR-762 expression relative to scrambled controls by ∼50%, increased expression of genes encoding RNase7 (∼80 %, ST2 (∼58% and Rab5a (∼75%, without affecting P. aeruginosa internalization. However, P. aeruginosa invasion was increased > 3-fold by a miR-762 mimic which reduced RNase7 and ST2 gene expression. Tear fluid alone also induced miR-762 expression ∼ 4-fold, which was reduced by the miR-762 antagomir. Combination of tear fluid and miR-762 antagomir increased RNase7 and ST2 gene expression. These data show that mucosal fluids, such as tears, can modulate epithelial microRNA expression to regulate innate defense genes, and that miR-762 negatively regulates RNase7, ST2 and Rab5a genes. Since RNase7 and ST2 inhibit P. aeruginosa internalization, and are upregulated by tear fluid, other tear-induced mechanisms must counteract inhibitory effects of miR-762 to regulate resistance to bacteria. These data also suggest a complex relationship between tear induction of miR-762, its modulation of innate defense genes, and P. aeruginosa internalization.

  3. Antibacterial Applications of Nanodiamonds

    Directory of Open Access Journals (Sweden)

    Sabine Szunerits

    2016-04-01

    Full Text Available Bacterial infectious diseases, sharing clinical characteristics such as chronic inflammation and tissue damage, pose a major threat to human health. The steady increase of multidrug-resistant bacteria infections adds up to the current problems modern healthcare is facing. The treatment of bacterial infections with multi-resistant germs is very difficult, as the development of new antimicrobial drugs is hardly catching up with the development of antibiotic resistant pathogens. These and other considerations have generated an increased interest in the development of viable alternatives to antibiotics. A promising strategy is the use of nanomaterials with antibacterial character and of nanostructures displaying anti-adhesive activity against biofilms. Glycan-modified nanodiamonds (NDs revealed themselves to be of great promise as useful nanostructures for combating microbial infections. This review summarizes the current efforts in the synthesis of glycan-modified ND particles and evaluation of their antibacterial and anti-biofilm activities.

  4. Antibacterial Applications of Nanodiamonds.

    Science.gov (United States)

    Szunerits, Sabine; Barras, Alexandre; Boukherroub, Rabah

    2016-04-01

    Bacterial infectious diseases, sharing clinical characteristics such as chronic inflammation and tissue damage, pose a major threat to human health. The steady increase of multidrug-resistant bacteria infections adds up to the current problems modern healthcare is facing. The treatment of bacterial infections with multi-resistant germs is very difficult, as the development of new antimicrobial drugs is hardly catching up with the development of antibiotic resistant pathogens. These and other considerations have generated an increased interest in the development of viable alternatives to antibiotics. A promising strategy is the use of nanomaterials with antibacterial character and of nanostructures displaying anti-adhesive activity against biofilms. Glycan-modified nanodiamonds (NDs) revealed themselves to be of great promise as useful nanostructures for combating microbial infections. This review summarizes the current efforts in the synthesis of glycan-modified ND particles and evaluation of their antibacterial and anti-biofilm activities.

  5. Antibacterial Au nanostructured surfaces

    Science.gov (United States)

    Wu, Songmei; Zuber, Flavia; Brugger, Juergen; Maniura-Weber, Katharina; Ren, Qun

    2016-01-01

    We present here a technological platform for engineering Au nanotopographies by templated electrodeposition on antibacterial surfaces. Three different types of nanostructures were fabricated: nanopillars, nanorings and nanonuggets. The nanopillars are the basic structures and are 50 nm in diameter and 100 nm in height. Particular arrangement of the nanopillars in various geometries formed nanorings and nanonuggets. Flat surfaces, rough substrate surfaces, and various nanostructured surfaces were compared for their abilities to attach and kill bacterial cells. Methicillin-resistant Staphylococcus aureus, a Gram-positive bacterial strain responsible for many infections in health care system, was used as the model bacterial strain. It was found that all the Au nanostructures, regardless their shapes, exhibited similar excellent antibacterial properties. A comparison of live cells attached to nanotopographic surfaces showed that the number of live S. aureus cells was technological platform for engineering Au nanotopographies by templated electrodeposition on antibacterial surfaces. Three different types of nanostructures were fabricated: nanopillars, nanorings and nanonuggets. The nanopillars are the basic structures and are 50 nm in diameter and 100 nm in height. Particular arrangement of the nanopillars in various geometries formed nanorings and nanonuggets. Flat surfaces, rough substrate surfaces, and various nanostructured surfaces were compared for their abilities to attach and kill bacterial cells. Methicillin-resistant Staphylococcus aureus, a Gram-positive bacterial strain responsible for many infections in health care system, was used as the model bacterial strain. It was found that all the Au nanostructures, regardless their shapes, exhibited similar excellent antibacterial properties. A comparison of live cells attached to nanotopographic surfaces showed that the number of live S. aureus cells was information (ESI) available. See DOI: 10.1039/c5nr06157a

  6. Antibacterial activity of Pterocarpus santalinus

    OpenAIRE

    Manjunatha B

    2006-01-01

    Antibacterial activity of leaf and stem bark of Pterocarpus santalinus (Fabaceae) was investigated. The antibacterial activity was tested against both Gram-positive and Gram-negative organisms. Among the two extracts tested, stem bark extract exhibited broad-spectrum antibacterial activity against the tested organisms. The stem bark extract showed maximum activity against Enterobacter aerogenes, Alcaligenes faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus cere...

  7. Antibacterial agents in the cinema.

    Science.gov (United States)

    García Sánchez, J E; García Sánchez, E; Merino Marcos, M L

    2006-12-01

    Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.

  8. Innate defense regulator peptide 1018 in wound healing and wound infection.

    Directory of Open Access Journals (Sweden)

    Lars Steinstraesser

    Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

  9. Skin Infection Management Using Novel Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Nejla Ahmadiyan

    2013-02-01

    Full Text Available Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA cause difficulties in the management of skin and soft tissue infections and have led to morbidity and mortality in hospital-acquired infections especially in susceptible individuals, those who are generally sick or immunosuppressed. Currently approaches in antibacterial agents offer opportunities to manage the trouble using novel anti-infection systems. Therefore, nanotechnology, a most promising field for generating new applications in medicine, has introduced a most prominent nanoproduct named as nanosilver that revealed excellent antimicrobial activity against some of the hazardous infections. Also cathelicidin peptides which are a part of native immune defense system in the skin and epithelia exhibit excellent antimicrobial activity against some of these perilous infections.

  10. Molecular interactions between the specialist herbivore Manduca sexta (Lepidoptera, Sphingidae) and its natural host Nicotiana attenuata. I. Large-scale changes in the accumulation of growth- and defense-related plant mRNAs.

    Science.gov (United States)

    Hermsmeier, D; Schittko, U; Baldwin, I T

    2001-02-01

    Plants respond to herbivore attack with a dramatic functional reorganization that involves the activation of direct and indirect defenses and tolerance, which in turn make large demands on primary metabolism. Here we provide the first characterization of the transcriptional reorganization that occurs after insect attack in a model plant-herbivore system: Nicotiana attenuata Torr. ex Wats.-Manduca sexta. We used mRNA differential display to characterize one-twentieth of the insect-responsive transcriptome of N. attenuata and verified differential expression for 27 cDNAs. Northern analyses were used to study the effects of folivory and exposure to airborne methyl jasmonate and for kinetic analyses throughout a 16-h- light/8-h-dark cycle. Sequence similarity searches allowed putative functions to be assigned to 15 transcripts. Genes were related to photosynthesis, electron transport, cytoskeleton, carbon and nitrogen metabolism, signaling, and a group responding to stress, wounding, or invasion of pathogens. Overall, transcripts involved in photosynthesis were strongly down-regulated, whereas those responding to stress, wounding, and pathogens and involved in shifting carbon and nitrogen to defense were strongly up-regulated. The majority of transcripts responded similarly to airborne methyl jasmonate and folivory, and had tissue- and diurnal-specific patterns of expression. Transcripts encoding Thr deaminase (TD) and a putative retrotransposon were absent in control plants, but were strongly induced after herbivory. Full-length sequences were obtained for TD and the pathogen-inducible alpha-dioxygenase, PIOX. Effects of abiotic and biotic stimuli were investigated for transcripts encoding TD, importin alpha, PIOX, and a GAL83-like kinase cofactor. PMID:11161026

  11. Host Defence to Pulmonary Mycosis

    Directory of Open Access Journals (Sweden)

    Christopher H Mody

    1999-01-01

    Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.

  12. Antibacterial activities of antineoplastic agents.

    OpenAIRE

    Bodet, C A; Jorgensen, J H; Drutz, D J

    1985-01-01

    Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities.

  13. Moving Target Defense

    CERN Document Server

    Jajodia, Sushil; Swarup, Vipin; Wang, Cliff; Wang, X Sean

    2011-01-01

    Moving Target Defense: Creating Asymmetric Uncertainty for Cyber Threats was developed by a group of leading researchers. It describes the fundamental challenges facing the research community and identifies new promising solution paths. Moving Target Defense which is motivated by the asymmetric costs borne by cyber defenders takes an advantage afforded to attackers and reverses it to advantage defenders. Moving Target Defense is enabled by technical trends in recent years, including virtualization and workload migration on commodity systems, widespread and redundant network connectivity, instr

  14. Takeover Defenses and Competition

    OpenAIRE

    Martijn Cremers; Vinay Nair; Urs Peyer

    2007-01-01

    This paper studies the interaction between takeover defenses and product market competition. We find that firms in more competitive industries have more takeover defenses. This is the opposite result from what one would expect if takeover defenses always constitute an inefficient outcome that increases agency costs and managerial entrenchment. A novel explantion is provided by considering the nature of the relationship between the firm and the product (or labor) market. For firms in industrie...

  15. Norwegian cyber defense

    OpenAIRE

    Stensboel, Karl Birger

    2013-01-01

    Approved for public release; distribution is unlimited. This thesis postulates the need for a more proactive approach to cyber defense in Norway and offers recommendations about how Norway can be better prepared to counter cyber threats. It finds that Norways strategic infrastructure is vulnerable to cyber attacks and that Norway has no coherent strategy for meeting this challenge. The thesis argues that an effective cyber defense requires a wide range of offensive and defensive measures a...

  16. Carbon Nanomaterials as Antibacterial Colloids

    Directory of Open Access Journals (Sweden)

    Michael Maas

    2016-07-01

    Full Text Available Carbon nanomaterials like graphene, carbon nanotubes, fullerenes and the various forms of diamond have attracted great attention for their vast potential regarding applications in electrical engineering and as biomaterials. The study of the antibacterial properties of carbon nanomaterials provides fundamental information on the possible toxicity and environmental impact of these materials. Furthermore, as a result of the increasing prevalence of resistant bacteria strains, the development of novel antibacterial materials is of great importance. This article reviews current research efforts on characterizing the antibacterial activity of carbon nanomaterials from the perspective of colloid and interface science. Building on these fundamental findings, recent functionalization strategies for enhancing the antibacterial effect of carbon nanomaterials are described. The review concludes with a comprehensive outlook that summarizes the most important discoveries and trends regarding antibacterial carbon nanomaterials.

  17. Helical 1:1 α/Sulfono-γ-AA Heterogeneous Peptides with Antibacterial Activity.

    Science.gov (United States)

    She, Fengyu; Nimmagadda, Alekhya; Teng, Peng; Su, Ma; Zuo, Xiaobing; Cai, Jianfeng

    2016-05-01

    As one of the greatest threats facing the 21st century, antibiotic resistance is now a major public health concern. Host-defense peptides (HDPs) offer an alternative approach to combat emerging multi-drug-resistant bacteria. It is known that helical HDPs such as magainin 2 and its analogs adopt cationic amphipathic conformations upon interaction with bacterial membranes, leading to membrane disruption and subsequent bacterial cell death. We have previously shown that amphipathic sulfono-γ-AApeptides could mimic magainin 2 and exhibit bactericidal activity. In this article, we demonstrate for the first time that amphipathic helical 1:1 α/sulfono-γ-AA heterogeneous peptides, in which regular amino acids and sulfono-γ-AApeptide building blocks are alternatively present in a 1:1 pattern, display potent antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens. Small angle X-ray scattering (SAXS) suggests that the lead sequences adopt defined helical structures. The subsequent studies including fluorescence microscopy and time-kill experiments indicate that these hybrid peptides exert antimicrobial activity by mimicking the mechanism of HDPs. Our findings may lead to the development of HDP-mimicking antimicrobial peptidomimetics that combat drug-resistant bacterial pathogens. In addition, our results also demonstrate the effective design of a new class of helical foldamer, which could be employed to interrogate other important biological targets such as protein-protein interactions in the future. PMID:27030636

  18. 不同寄主多主棒孢对橡胶树叶片组织防御酶活性的影响%Influence of Corynespora cassiicola Isolated from Different Hosts on Defensive Enzymes Activities in the Leaves of Hevea brasiliensis

    Institute of Scientific and Technical Information of China (English)

    蔡丽; 王延丽; 林春花; 黄贵修

    2011-01-01

    以分离自4种寄主的5株多主棒孢菌株接种橡胶树叶片,均得到成功侵染.并按时间顺序测定了来自不同寄主的多主棒孢侵染橡胶树叶片后,细胞防御系统相关的4种酶活性的变化.结果表明,接种来自不同寄主的多主棒孢后,对橡胶树叶片4种防御酶活性的影响不同.其中分离自橡胶树的HCCGD01和HCCHN42两个菌株侵染后,橡胶树叶片组织4种防御酶活性变化最大,均有明显增强;来自木薯的MaCCGD02侵染橡胶树叶片后,酶活性变化次之;分离自番木瓜的CpCCYN01和黄瓜的PaCCSD04多主棒孢菌株侵染后,除PAL外,β-1,3-葡聚糖酶、POD、PP0活性变化很小.%The influence of Corynespora cassiicola isolated from 4 different hosts on defensive enzymes activities (|3-l,3-glucanase, POD, PAL, PPO) in the leaves of Hevea brasiliensis was studied in this paper. The results showed that the changes of 4 kinds of defensive enzymes activities in the leaves of Hevea brasiliensis were different with inoculated Corynespora cassiicola isolated from different hosts. The activities of these defensive enzymes quickly enhanced after inoculation by the pathogens (HCCGD01 and HCCHN42) isolated from Hevea brasiliensis, and slower increase in leaves inoculated by MaCCGD02 isolated from cassava. However the activities of |3-l,3-glucanase, POD, PPO almost unchanged when the leaves were infected by PaCCSD04 from cucumber and CpCCYNOl from papaya.

  19. Defense at the lung lining: antifungal activities of SP-D and LL-37

    NARCIS (Netherlands)

    Ordonez, Soledad R

    2016-01-01

    Host defense proteins and peptides are part of the innate immune system of the lung. They constitute one of the first defenses against fungal pathogens during inhalation. Discerning how these molecular defenses act in concert to prevent infection in a healthy lung has proven to be difficult, due to

  20. The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery

    OpenAIRE

    Wright, Peter M.; Seiple, Ian B.; Myers, Andrew G.

    2014-01-01

    The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequ...

  1. Defense Mechanisms: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  2. Forgiveness and Defense Style

    Science.gov (United States)

    Maltby, John; Day, Liz

    2004-01-01

    Within the literature on the psychology of forgiveness, researchers have hypothesized that the 1st stage in the process of being able to forgive is the role of psychological defense. To examine such a hypothesis, the authors explored the relationship between forgiveness and defense style. The 304 respondents (151 men, 153 women) completed measures…

  3. Treatment of candidiasis: insights from host genetics.

    Science.gov (United States)

    Delsing, Corine E; Bleeker-Rovers, Chantal P; Kullberg, Bart-Jan; Netea, Mihai G

    2012-08-01

    Candida species are major causes of mucosal and invasive infections, leading to substantial morbidity and mortality. Despite the development of new classes of antifungal drugs, mortality in patients with systemic candidiasis remains high. Host-Candida interaction plays an important role in effective elimination of the pathogen. Genetic studies have rendered important insights into antifungal host defense and have identified potential targets for adjunctive therapy. In this article, the authors review the genetic variations in the host defense to Candida and their implications for the treatment of mucosal and systemic candidiasis.

  4. Antibacterial activity of Pterocarpus santalinus

    Directory of Open Access Journals (Sweden)

    Manjunatha B

    2006-01-01

    Full Text Available Antibacterial activity of leaf and stem bark of Pterocarpus santalinus (Fabaceae was investigated. The antibacterial activity was tested against both Gram-positive and Gram-negative organisms. Among the two extracts tested, stem bark extract exhibited broad-spectrum antibacterial activity against the tested organisms. The stem bark extract showed maximum activity against Enterobacter aerogenes, Alcaligenes faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus . The leaf extract showed maximum activity against Escherichia coli, Alcaligenes faecalis, Enterobacter aerogenes and Pseudomonas aeruginosa . Both extracts exhibited concentration dependent activity.

  5. Defense Industry Clusters in Turkey

    Directory of Open Access Journals (Sweden)

    Kadir Alpaslan Demir

    2016-06-01

    Full Text Available All countries strive for a capable national defense supported by a strong national defense industry. Supporting national defense with imported defense systems has many limitations and risks because the terms of arms trade agreements between countries may easily be influenced by the political climate of the signatories. As a result, establishing an independent national defense requires a strong national defense industry. Furthermore, exporting defense systems may be an important source of national income. National defense industries mostly consist of large-scale defense firms that have the resources required for big defense contracts. However, small to medium enterprises (SMEs do not have the necessary resources, therefore they are at a disadvantage. To overcome this handicap and be part of the business, defense industry clusters mostly consisting of SMEs are being established. Provided that there is good national planning and support in this area, defense clusters consisting of SMEs may play a significant role in industry. SMEs have a chance to offer specialized services, special or customized products when needed. As a result, large defense firms subcontract certain portions of defense projects to SMEs. Since 2010, Turkey has shown signs of continuous improvement in defense industry clustering. In parallel with these developments, this study discusses the importance of clustering in the defense industry, briefly presents the state of the Turkish defense industry as highlighted by national statistics, and presents the current status of defense clusters in Turkey. The novelty of this article consists in its assessment of Turkish defense clusters.

  6. Unfolding Green Defense

    DEFF Research Database (Denmark)

    Larsen, Kristian Knus

    2015-01-01

    consumption in military operations, defense expenditure, energy security, and global climate change. The report then proceeds to introduce the NATO Green Defence Framework before exploring specific current uses of green technologies and green strategies for defense. The report concludes that a number...... of political, military, organizational, and technological challenges and possibilities are related to the development of green solutions for defense. Based on this conclusion the report argues that it is essential to comprehensively describe how a green solution is linked to a security challenge to develop...

  7. Oral Immune Defense against Chronic Hyperplastic Candidosis

    OpenAIRE

    Musrati, Ahmed S Ali

    2008-01-01

    Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrie...

  8. Macrophage defense mechanisms against intracellular bacteria.

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  9. Differential post-surgical metastasis and survival in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null mice with parental and subline variants of human breast cancer: implications for host defense mechanisms regulating metastasis.

    Directory of Open Access Journals (Sweden)

    Chloe C Milsom

    Full Text Available We compare for the first time, the metastatic aggressiveness of the parental MDA-MB-231 breast cancer cell line and two luciferase-tagged in vivo-derived and selected pro-metastatic variants (LM2-4/luc⁺ and 164/8-1B/luc⁺ in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null (NSG mice following orthotopic implantation and primary tumour resection. The variants are known to be more aggressively metastatic in SCID mice, compared to the parental line which has limited spontaneous metastatic competence in these mice. When 2×10⁶ cells were injected into the mammary fat pad, the growth of the resultant primary tumours was identical for the various cell lines in the three strains of mice. However, metastatic spread of all three cell lines, including the MDA-MB-231 parental cell line, was strikingly more aggressive in the highly immunocompromised NSG mice compared to both NOD-SCID and SCID mice, resulting in extensive multi-organ metastases and a significant reduction in overall survival. While these studies were facilitated by monitoring post-surgical spontaneous metastases using whole body bioluminescence imaging, we observed that the luciferase-tagged parental line showed altered growth and diminished metastatic properties compared to its untagged counterpart. Our results are the first to show that host immunity can have a profound impact on the spread of spontaneous visceral metastases and survival following resection of a primary tumour in circumstances where the growth of primary tumours is not similarly affected; as such they highlight the importance of immunity in the metastatic process, and by extension, suggest certain therapeutic strategies that may have a significant impact on reducing metastasis.

  10. Defense Mechanisms in Adolescence.

    Science.gov (United States)

    Cramer, Phebe

    1979-01-01

    Results showed that by ninth or tenth grade, males begin to externalize conflict while females tend to deal with conflict internally. This differentiation of defense choice by sex is clearly established by the last two years of high school. (JMB)

  11. Surfing China's National Defense

    Institute of Scientific and Technical Information of China (English)

    Ji Guilin

    2010-01-01

    @@ Following the start of its first test run on August 20, 2009, the website www.mod.gov.cn of the Ministry of National Defense (MOD) of the People's Republic of China has logged more than 2 billion hits,from many countries and regions including China, the United States,the United Kingdom, Japan, Australia and Singapore. China National Defense News reporters recently interviewed Ji Guilin, the website's Editor in Chief, on its performance and the feedback of netizens.

  12. Auxins in defense strategies

    OpenAIRE

    Čarná, M. (Mária); Repka, V.; Skůpa, P. (Petr); Šturdík, E.

    2014-01-01

    Plant hormones operate in a very complex network where they regulate and control different vital mechanisms. They coordinate growth, development and defense via signaling involving different interactions of molecules. Activation of molecules responsible for regulation of plant immunity is mainly provided by salicylic and jasmonic acid signaling pathways. Similar to the signaling of these defense-associated plant hormones, auxin can also affect resistance to different pathogen groups and disea...

  13. Nest defenses and egg recognition of yellow-bellied prinia against cuckoo parasitism

    Science.gov (United States)

    Yang, Canchao; Wang, Longwu; Cheng, Shun-Jen; Hsu, Yu-Cheng; Liang, Wei; Møller, Anders Pape

    2014-09-01

    Parasites may, in multi-parasite systems, block the defenses of their hosts and thus thwart host recognition of parasites by frequency-dependent selection. Nest defenses as frontline may block or promote the subsequent stage of defenses such as egg recognition. We conducted comparative studies of the defensive strategies of a host of the Oriental cuckoo Cuculus optatus, the yellow-bellied prinia Prinia flaviventris, in mainland China with multiple species of cuckoos and in Taiwan with a single cuckoo species. Cuckoo hosts did not exhibit aggression toward cuckoos in the presence of multiple cuckoo species but showed strong aggressive defenses of hosts directed toward cuckoos in Taiwan. Furthermore, the cuckoo host in populations with a single cuckoo species was able to distinguish adults of its brood parasite, the Oriental cuckoo, from adult common cuckoos ( Cuculus canorus). This represents the first case in which a cuckoo host has been shown to specifically distinguish Oriental cuckoo, from other Cuculus species. Hosts ejected eggs at a higher rate in a single cuckoo species system than in a multi-species cuckoo system, which supports the strategy facilitation hypothesis. Granularity analysis of variation in egg phenotype based on avian vision modeling supported the egg signature hypothesis in hosts because Taiwanese prinias increased consistency in the appearance of their eggs within individual hosts thus favoring efficient discrimination against cuckoo eggs. This study significantly improves our knowledge of intraspecific variation in antiparasitism behavior of hosts between single- and multi-cuckoo systems.

  14. Defense-Inducing Volatiles: In Search of the Active Motif

    OpenAIRE

    Heil, Martin; Lion, Ulrich; Boland, Wilhelm

    2008-01-01

    Herbivore-induced volatile organic compounds (VOCs) are widely appreciated as an indirect defense mechanism since carnivorous arthropods use VOCs as cues for host localization and then attack herbivores. Another function of VOCs is plant–plant signaling. That VOCs elicit defensive responses in neighboring plants has been reported from various species, and different compounds have been found to be active. In order to search for a structural motif that characterizes active VOCs, we used lima be...

  15. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia

    OpenAIRE

    Hilliard, Kristie L.; Allen, Eri; Traber, Katrina E.; Kim, Yuri; Wasserman, Gregory A.; Jones, Matthew R.; Mizgerd, Joseph P.; Quinton, Lee J.

    2015-01-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis a...

  16. Antibacterial Mechanism of Copper-bearing Antibacterial Stainless Steel against E.Coli

    Institute of Scientific and Technical Information of China (English)

    Li NAN; Weichao YANG; Yongqian LIU; Hui XU; Ying LI; Manqi L(U); Ke YANG

    2008-01-01

    A preliminary study was made on the antibacterial mechanism of copper-bearing antibacterial stainless steels against E.coli through experiments of microbiology such as EDTA (ethylenediaminetetraacetic acid) complex- ing, DNA smearing and AFM (atomic force microscope) observation. It was measured that the antibacterial stainless steels showed excellent antibacterial functions with antibacterial rate to E.coli over 99.99%. The antibacterial rate was weak if the bacteria solution was complexed by EDTA, indicating that the copper ions play a dominant role in the antibacterial effect of the antibacterial stainless steels. The electrophoresis experi- ment did not show the phenomenon of DNA smearing for E.coli after contacting antibacterial stainless steels, which meant that DNA of E.coli was not obviously damaged. It was observed by AFM that the morphology of E.coli changed a lot after contacting antibacterial stainless steels, such as cell walls being seriously changed and lots of contents in the cells being leaked.

  17. Antibacterial Cleaning Products and Drug Resistance

    OpenAIRE

    Aiello, Allison E.; Marshall, Bonnie; Levy, Stuart B.; Della-Latta, Phyllis; Lin, Susan X.; Larson, Elaine

    2005-01-01

    We examined whether household use of antibacterial cleaning and hygiene products is an emerging risk factor for carriage of antimicrobial drug–resistant bacteria on hands of household members. Households (N = 224) were randomized to use of antibacterial or nonantibacterial cleaning and hygiene products for 1 year. Logistic regression was used to assess the influence of antibacterial product use in homes. Antibacterial product use did not lead to a significant increase in antimicrobial drug re...

  18. Defense waste management plan

    International Nuclear Information System (INIS)

    Defense high-level waste (HLW) and defense transuranic (TRU) waste are in interim storage at three sites, namely: at the Savannah River Plant, in South Carolina; at the Hanford Reservation, in Washington; and at the Idaho National Engineering Laboratory, in Idaho. Defense TRU waste is also in interim storage at the Oak Ridge National Laboratory, in Tennessee; at the Los Alamos National Laboratory, in New Mexico; and at the Nevada Test Site, in Nevada. (Figure E-2). This document describes a workable approach for the permanent disposal of high-level and transuranic waste from atomic energy defense activities. The plan does not address the disposal of suspect waste which has been conservatively considered to be high-level or transuranic waste but which can be shown to be low-level waste. This material will be processed and disposed of in accordance with low-level waste practices. The primary goal of this program is to utilize or dispose of high-level and transuranic waste routinely, safely, and effectively. This goal will include the disposal of the backlog of stored defense waste. A Reference Plan for each of the sites describes the sequence of steps leading to permanent disposal. No technological breakthroughs are required to implement the reference plan. Not all final decisions concerning the activities described in this document have been made. These decisions will depend on: completion of the National Environmental Policy Act process, authorization and appropriation of funds, agreements with states as appropriate, and in some cases, the results of pilot plant experiments and operational experience. The major elements of the reference plan for permanent disposal of defense high-level and transuranic waste are summarized

  19. Antibacterial Properties of an Austenitic Antibacterial Stainless Steel and Its Security for Human Body

    Institute of Scientific and Technical Information of China (English)

    Ke YANG; Manqi L(U)

    2007-01-01

    An austenitic antibacterial stainless steel is reported in this paper. The very fine and dispersive ε-Cu precipitations in the matrix of the antibacterial steel after the antibacterial treatment endow the steel with antibacterial function. The antibacterial function is strong, long-term and broad-spectrum, and can be maintained even after repeated wear and long time dipping in water. The steel is safe for human body and could be used widely in daily application.

  20. Cloning, expression, and purification of a new antibacterial substance gene from larvae of Musca domestica (Diptera: Muscidae).

    Science.gov (United States)

    Pei, Zhihua; Bian, Lu; Zhang, Hui; Gao, Yunhang; Ma, Hongxia

    2014-01-01

    Musca domestica L. (Diptera: Muscidae), the housefly, exhibits unique immune defenses and can produce antibacterial substances upon stimulation with bacteria. On the basis of the cDNA library constructed using the suppression subtractive hybridization method, a 1188-bp antibacterial substance gene, which we named AS566, was amplified by rapid amplification of cDNA ends from M. domestica larva stimulated with Salmonella pullorum (Enterobacteriaceae: Salmonella). In this study, the full-length AS566 gene was cloned and inserted into a His-tagged Escherichia coli (Enterobacteriaceae: Escherichia) prokaryotic expression system to enable production of the recombinant protein. The recombinant AS566 protein was purified in denatured form from inclusion bodies and renatured to obtain functionally active AS566 protein. The bacteriostatic activity of the recombinant purified AS566 protein was assessed using the Oxford plate assay system and the results indicated that AS566 had antibacterial activity against six bacteria, including an E. coli clinical isolate, S. pullorum, Streptococcus bovis (Streptococcaceae: Streptococcus), Streptococcus suis, and Staphylococcus aureus (Staphylococcaceae: Staphylococcus) in vitro. The antibacterial activity of AS566 toward Gram- bacteria was two times greater than that against Gram+ bacteria. The sequencing results and BLAST analysis showed that the antibacterial substance gene AS566 was not homologous to any other antibacterial substance genes in GenBank. The antibacterial mechanisms of the newly discovered AS566 protein warrant further study.

  1. Demeter's Resilience: an International Food Defense exercise.

    Science.gov (United States)

    Hennessey, Morgan; Kennedy, Shaun; Busta, Frank

    2010-07-01

    The National Center for Food Protection and Defense (NCFPD), which is led by the University of Minnesota, hosted an international food defense exercise on 27 to 29 May 2008. Established in 2004, NCFPD is a Department of Homeland Security Center of Excellence with the mission of defending the food system through research and education. Tabletop exercises are practice-based scenarios intended to mimic real life experiences. The objective of the exercise discussed in this article was to facilitate discussion to increase awareness among exercise participants of both the threat that would be posed by an intentional attack on the food supply and the international impact of such an attack. Through facilitated discussion, exercise participants agreed on the following themes: (i) recognition of a foodborne disease outbreak is driven by the characteristics of the illness rather than the actual number of ill individuals; (ii) during the course of a foodborne outbreak there are generally multiple levels of communication; (iii) a common case definition for a foodborne disease is difficult to develop on a global scale; and (iv) the safety and health of all individuals is the number one priority of all parties involved. Several challenges were faced during the development of the exercise, but these were overcome to produce a more robust exercise. The following discussion will provide an overview of the challenges and the strategies used to overcome them. The lessons learned provide insight into how to plan, prepare, and host an international food defense exercise. PMID:20615353

  2. 76 FR 28960 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2011-05-19

    ... of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of... a closed meeting of the Defense Intelligence Agency National Defense Intelligence College Board...

  3. 75 FR 76423 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2010-12-08

    ... of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of... a closed meeting of the Defense Intelligence Agency National Defense Intelligence College Board...

  4. 76 FR 28757 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-05-18

    ... of the Secretary Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Notice of Availability (NOA) of Revised Defense Logistics Agency Regulation. SUMMARY: The Defense...

  5. Bacterial Suppression of RNA Polymerase II-Dependent Host Gene Expression

    Directory of Open Access Journals (Sweden)

    Ines Ambite

    2016-07-01

    Full Text Available Asymptomatic bacteriuria (ABU is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli strains and therefore elicit weak innate immune responses in the urinary tract. In addition, ABU strains are active modifiers of the host environment, which they influence by suppressing RNA polymerase II (Pol II-dependent host gene expression. In patients inoculated with the ABU strain E. coli 83972, gene expression was markedly reduced after 24 h (>60% of all regulated genes. Specific repressors and activators of Pol II-dependent transcription were modified, and Pol II Serine 2 phosphorylation was significantly inhibited, indicating reduced activity of the polymerase. This active inhibition included disease–associated innate immune response pathways, defined by TLR4, IRF-3 and IRF-7, suggesting that ABU strains persist in human hosts by active suppression of the antibacterial defense. In a search for the mechanism of inhibition, we compared the whole genome sequences of E. coli 83972 and the uropathogenic strain E. coli CFT073. In addition to the known loss of virulence genes, we observed that the ABU strain has acquired several phages and identified the lytic Prophage 3 as a candidate Pol II inhibitor. Intact phage particles were released by ABU during in vitro growth in human urine. To address if Prophage 3 affects Pol II activity, we constructed a Prophage 3 negative deletion mutant in E. coli 83972 and compared the effect on Pol II phosphorylation between the mutant and the E. coli 83972 wild type (WT strains. No difference was detected, suggesting that the Pol II inhibitor is not encoded by the phage. The review summarizes the evidence that the ABU strain E. coli 83972 modifies host gene expression by inhibition of Pol II phosphorylation, and discusses the ability of ABU strains to actively create an

  6. Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity.

    Science.gov (United States)

    Fumakia, Miral; Ho, Emmanuel A

    2016-07-01

    Wound care is a serious healthcare concern, often complicated by prolonged inflammation and bacterial infection, which contributes significantly to mortality and morbidity. Agents commonly used to treat chronic wound infections are limited due to toxicity of the therapy, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide possessing antimicrobial activity and is involved in the modulation of wound healing. Serpin A1 (A1) is an elastase inhibitor and has been shown to demonstrate wound-healing properties. Hence, our goal was to develop a topical combination nanomedicine for the controlled sustained delivery of LL37 and A1 at precise synergistic ratio combinations that will significantly promote wound closure, reduce bacterial contamination, and enhance anti-inflammatory activity. We have successfully developed the first solid lipid nanoparticle (SLN) formulation that can simultaneously deliver LL37 and A1 at specific ratios resulting in accelerated wound healing by promoting wound closure in BJ fibroblast cells and keratinocytes as well as synergistically enhancing antibacterial activity against S. aureus and E. coli in comparison to LL37 or A1 alone. PMID:27182713

  7. Anti-bacterial Studies of Silver Nanoparticles

    CERN Document Server

    Theivasanthi, T

    2011-01-01

    We discuss about the antibacterial activities of Silver nanoparticles and compare them on both Gram negative and Gram positive bacteria in this investigation. The activities of Silver nanoparticles synthesized by electrolysis method are more in Gram (-) than Gram (+) bacteria. First time, we increase its antibacterial activities by using electrical power while on electrolysis synthesis and it is confirmed from its more antibacterial activities (For Escherichia coli bacteria). We investigate the changes of inner unit cell Lattice constant of Silver nanoparticles prepared in two different methods and its effects on antibacterial activities. We note that slight change of the lattice constant results in the enhancement of its antibacterial activities.

  8. Defense styles of pedophilic offenders.

    Science.gov (United States)

    Drapeau, Martin; Beretta, Véronique; de Roten, Yves; Koerner, Annett; Despland, Jean-Nicolas

    2008-04-01

    This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization. PMID:17875603

  9. Defense styles of pedophilic offenders.

    Science.gov (United States)

    Drapeau, Martin; Beretta, Véronique; de Roten, Yves; Koerner, Annett; Despland, Jean-Nicolas

    2008-04-01

    This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization.

  10. The bacteriome-mycobiome interaction and antifungal host defense

    NARCIS (Netherlands)

    Oever, J.T.; Netea, M.G.

    2014-01-01

    Large communities of microorganisms, collectively termed the microbiome, inhabit our body surfaces. With the advent of next-generation sequencing, the diversity and abundance of these communities are being unravelled. Besides an imporant role in metabolic processes, the microbiome is essential for p

  11. The role of opsonins in Aspergillus fumigatus host defense

    NARCIS (Netherlands)

    Braem, S.G.E.

    2015-01-01

    Aspergillus fumigatus is an important fungal pathogen and a common cause of invasive fungal infections in humans. Susceptible individuals become infected via the inhalation of dormant conidia.If the immune system fails to clear these conidia, they will swell, germinate and grow into large hyphal str

  12. The roles of cutaneous lipids in host defense.

    Science.gov (United States)

    Fischer, Carol L; Blanchette, Derek R; Brogden, Kim A; Dawson, Deborah V; Drake, David R; Hill, Jennifer R; Wertz, Philip W

    2014-03-01

    Lauric acid (C12:0) and sapienic acid (C16:1Δ6) derived from human sebaceous triglycerides are potent antimicrobials found at the human skin surface. Long-chain bases (sphingosine, dihydrosphingosine and 6-hydroxysphingosine) are also potent and broad-acting antimicrobials normally present at the skin surface. These antimicrobials are generated through the action of ceramidases on ceramides from the stratum corneum. These natural antimicrobials are thought to be part of the innate immune system of the skin. Exogenously providing these lipids to the skin may provide a new therapeutic option, or could potentially provide prophylaxis in people at risk of infection. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. PMID:23994607

  13. Cdc42 promotes host defenses against fatal infection

    DEFF Research Database (Denmark)

    Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V;

    2013-01-01

    The small Rho GTPase, Cdc42, regulates key signaling pathways required for multiple cell functions including maintenance of shape, polarity, proliferation, invasion, migration, differentiation and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we...... attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that...... were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also...

  14. Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia

    NARCIS (Netherlands)

    G.J.W. van der Windt; J.J. Hoogerwerf; A.F. de Vos; S. Florquin; T. van der Poll

    2010-01-01

    Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and

  15. Two Dioryctria Species with Different Survival Strategies to Adapt to Chemical Defense of Host Plant Pinus koraiensis%红松的化学防御及冷杉梢斑螟和赤松梢斑螟的生存策略

    Institute of Scientific and Technical Information of China (English)

    王琪; 严善春; 徐波

    2012-01-01

    Dioryctria abietella and D. sylvestrella are close relative species in the same genus, and both endanger cones of Pinus koraiensis concomitantly, but their biological and ecological behaviors are quite different. To investigate the interactions between the host P. koraiensis chemical defense and physiological adaptation of the two D. species, we analyzed the larvae midgut detoxication enzymes and protective enzymes activities in lth, 3rd, Sth instars, and the defense enzymes in healthy, fed pine cones or top shoots at the corresponding period. The results showed that phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activities in healthy cones and shoots were changed with the development stage. The two D. larvae feeding induced those defense enzymes activities significantly increased compared with healthy cones or tips. Detoxication enzymes and protective enzymes in the two D. species, which have different survival strategies, were quite different. D. abietella specifically fed on cone through larval stage, and their detoxication enzymes, S-transferase (GST), carboxylesterase (CarE), multi-function oxidase (MFO) in midgut were significantly higher than D. sylvestrella larvae that alternatively fed on cones and tips. There were no significant differences in superoxide dismutase (SOD) and chitinase (CT) activities in D. abietella and D. sylvestrella midgus, and the two protective enzymes activities were not related to whether transferred feeding. Phenoloxidase (PO) and peroxidase (POD) in D. sylvestrella midguts had higher activity compared with D. abietella, suggesting that the higher activity could facilitate them to avoid the threat of the transfer process. The results indicated that the physiological detoxification was the predominant survival strategies for D. abietella larvae to adapt to chemical defense of host plant, whereas D. sylvestrella larvae survived not only by carrying out the

  16. Animal Defenses against Infectious Agents: Is Damage Control More Important Than Pathogen Control?

    OpenAIRE

    Andrew F Read; Graham, Andrea L.; Lars Råberg

    2008-01-01

    The ability of hosts to withstand a given number of pathogens is a critical component of health. Now playing catch-up with plant biologists, animal biologists are starting to formally separate this form of defense from classical resistance.

  17. Bioassay Guided Isolation of Antibacterial Compounds from Andrographis paniculata

    Directory of Open Access Journals (Sweden)

    A. Sule

    2011-01-01

    Full Text Available Problem statement: Chronic disease-causing bacteria of medical importance have developed resistance to antibiotics, hence, necessitating distinct and constant need for safe and efficient therapeutic agents. Plants are considered potent candidate for this aim. A way out of reducing antibiotic resistance and adverse effects on host is the employment of antibiotic resistance inhibitors of plant origin. Approach: About 5 kg pulverized Andrographis paniculata whole plant was macerated with MeOH at room temperature to get 305 g freeze dried MeOH extract. The bioautography of MeOH extract using Staphylococcus aureus and Proteus mirabilis as indicator organisms revealed the presence of two potent antibacterial compounds. MeOH extract was further fractionated and purified by silica gel column chromatography which led to the isolation of a diterpene lactone and an entlabdane diterpene glycoside upon crystallization with absolute ethanol. Results: Two antibacterial compounds viz., 3-O-β-D-glucosyl-14-deoxyandrographolide and 14-deoxyandrographolide were successfully isolated and characterized. Their structures were exclusively elucidated through spectroscopic methods (UV, IR, 1H- and 13C NMR. Conclusion: A. paniculata possesses antibacterial activity and could be potential source of a new class of antibiotics that might be useful for infectious disease chemotherapy and control.

  18. Defense on the Move: Ant-Based Cyber Defense

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Glenn A.; Haack, Jereme N.; McKinnon, Archibald D.; Fulp, Errin W.

    2014-04-15

    Many common cyber defenses (like firewalls and IDS) are as static as trench warfare allowing the attacker freedom to probe them at will. The concept of Moving Target Defense (MTD) adds dynamism to the defender side, but puts the systems to be defended themselves in motion, potentially at great cost to the defender. An alternative approach is a mobile resilient defense that removes attackers’ ability to rely on prior experience without requiring motion in the protected infrastructure itself. The defensive technology absorbs most of the cost of motion, is resilient to attack, and is unpredictable to attackers. The Ant-Based Cyber Defense (ABCD) is a mobile resilient defense providing a set of roaming, bio-inspired, digital-ant agents working with stationary agents in a hierarchy headed by a human supervisor. The ABCD approach provides a resilient, extensible, and flexible defense that can scale to large, multi-enterprise infrastructures like the smart electric grid.

  19. Inactivation of indispensable bacterial proteins by early proteins of bacteriophages: implication in antibacterial drug discovery.

    Science.gov (United States)

    Sau, S; Chattoraj, P; Ganguly, T; Chanda, P K; Mandal, N C

    2008-06-01

    Bacteriophages utilize host bacterial cellular machineries for their own reproduction and completion of life cycles. The early proteins that phage synthesize immediately after the entry of their genomes into bacterial cells participate in inhibiting host macromolecular biosynthesis, initiating phage-specific replication and synthesizing late proteins. Inhibition of synthesis of host macromolecules that eventually leads to cell death is generally performed by the physical and/or chemical modification of indispensable host proteins by early proteins. Interestingly, most modified bacterial proteins were shown to take part actively in phage-specific transcription and replication. Research on phages in last nine decades has demonstrated such lethal early proteins that interact with or chemically modify indispensable host proteins. Among the host proteins inhibited by lethal phage proteins, several are not inhibited by any chemical inhibitor available today. Under the context of widespread dissemination of antibiotic-resistant strains of pathogenic bacteria in recent years, the information of lethal phage proteins and cognate host proteins could be extremely invaluable as they may lead to the identification of novel antibacterial compounds. In this review, we summarize the current knowledge about some early phage proteins, their cognate host proteins and their mechanism of action and also describe how the above interacting proteins had been exploited in antibacterial drug discovery. PMID:18537683

  20. The plastic response of Manduca sexta to host and non-host plants.

    Science.gov (United States)

    Koenig, Christopher; Bretschneider, Anne; Heckel, David G; Grosse-Wilde, Ewald; Hansson, Bill S; Vogel, Heiko

    2015-08-01

    Specialist insect herbivores have evolved efficient ways to adapt to the major defenses of their host plants. Although Manduca sexta, specialized on Solanaceous plants, has become a model organism for insect molecular biology, little is known about its adaptive responses to the chemical defenses of its hosts. To study larval performance and transcriptomic responses to host and non-host plants, we conducted developmental assays and replicated RNAseq experiments with Manduca larvae fed on different Solanaceous plants as well as on a Brassicaceous non-host plant, Brassica napus. Manduca larvae developed fastest on Nicotiana attenuata, but no significant differences in performance were found on larvae fed on other Solanaceae or the non-host B. napus. The RNAseq experiments revealed that Manduca larvae display plastic responses at the gene expression level, and transcriptional signatures specific to the challenges of each host- and non-host plant. Our observations are not consistent with expectations that specialist herbivores would perform poorly on non-host plants. Instead, our findings demonstrate the ability of this specialized insect herbivore to efficiently use a larger repertoire of host plants than it utilizes in the field. PMID:26070471

  1. Colorado potato beetle manipulates plant defenses in local and systemic leaves

    OpenAIRE

    Chung, Seung Ho; Rosa, Cristina; Hoover, Kelli; Luthe, Dawn S; Felton, Gary W.

    2013-01-01

    Herbivore microbial associates can affect diverse interactions between plants and insect herbivores. Some insect symbionts enable herbivores to expand host plant range or to facilitate host plant use by modifying plant physiology. However, little attention has been paid to the role of herbivore-associated microbes in manipulating plant defenses. We have recently shown that Colorado potato beetle secrete the symbiotic bacteria to suppress plant defenses. The bacteria in oral secretions from th...

  2. High Selective Performance of Designed Antibacterial and Anticancer Peptide Amphiphiles.

    Science.gov (United States)

    Chen, Cuixia; Chen, Yucan; Yang, Cheng; Zeng, Ping; Xu, Hai; Pan, Fang; Lu, Jian Ren

    2015-08-12

    Short designed peptide amphiphiles are attractive at killing bacteria and inhibiting cancer cell growth, and the flexibility in their structural design offers a great potential for improving their potency and biocompatibility to mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n≥3) have been shown to be membrane lytic, but terminal amino acid modifications could impose a huge influence on their performance. We report in this work how terminal amino acid modifications to G(IIKK)3I-NH2 influence its α-helical structure, membrane penetrating ability, and selective actions against different cell types. Deletion of an N-terminal Gly or a C-terminal Ile did not affect their antibacterial activity much, an observation consistent with their binding behavior to negatively charged membrane lipid monolayers. However, the cytotoxicity against mammalian cells was much worsened by the N-terminal Gly deletion, consistent with an increase in its helical content. Despite little impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal amino acids greatly reduced its antitumor activity. Cholesterol present in tumor cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into the cancerous membranes, evident from its lowest surface physical activity at penetrating model lipid membranes. On the other hand, its low toxicity to normal mammalian cells and high antibacterial activity in vitro and in vivo made it an attractive antibacterial agent. Thus, terminal modifications can help rebalance the different interactions involved and are highly effective at manipulating their selective membrane responses.

  3. Inducible direct plant defense against insect herbivores: A review

    Institute of Scientific and Technical Information of China (English)

    Ming-Shun Chen

    2008-01-01

    Plants respond to insect herbivory with responses broadly known as direct defenses, indirect defenses, and tolerance. Direct defenses include all plant traits that affect susceptibility of host plants by themselves. Overall categories of direct plant defenses against insect herbivores include limiting food supply, reducing nutrient value, reducing preference, disrupting physical structures, and inhibiting chemical pathways of the attacking insect. Major known defense chemicals include plant secondary metabolites, protein inhibitors of insect digestive enzymes, proteases, lectins, amino acid deaminases and oxidases. Multiple factors with additive or even synergistic impact are usually involved in defense against a specific insect species, and factors of major importance to one insect species may only be of secondary importance or not effective at all against another insect species. Extensive qualitative and quantitative high throughput analyses of temporal and spatial variations in gene expression, protein level and activity, and metabolite concentration will accelerate not only the understanding of the overall mechanisms of direct defense, but also accelerate the identification of specific targets for enhancement of plant resistance for agriculture.

  4. Effective but costly, evolved mechanisms of defense against a virulent opportunistic pathogen in Drosophila melanogaster.

    OpenAIRE

    Yixin H Ye; Chenoweth, Stephen F.; McGraw, Elizabeth A.

    2009-01-01

    Drosophila harbor substantial genetic variation for antibacterial defense, and investment in immunity is thought to involve a costly trade-off with life history traits, including development, life span, and reproduction. To understand the way in which insects invest in fighting bacterial infection, we selected for survival following systemic infection with the opportunistic pathogen Pseudomonas aeruginosa in wild-caught Drosophila melanogaster over 10 generations. We then examined genome-wide...

  5. Antibacterial potency screening of Capparis zeylanica Linn

    Institute of Scientific and Technical Information of China (English)

    Rezaul Haque; Wahedul Islam; Selina Parween

    2016-01-01

    Objective: To conduct the antibacterial potency and minimum inhibitory concentration of extracts (n-hexane, acetone, chloroform and methanol) obtained from the root, leaf and stem of Capparis zeylanica. Methods: The powdered leaf, root and stem samples were Soxhlet extracted sequentially in n-hexane, acetone, chloroform and methanol. Antibacterial potency was evaluated by following the agar diffusion method and amoxicillin disc was used as a control. Results: In vitro antibacterial activity against 12 bacteria was performed with crude extracts. Among them, all the bacteria showed the moderate activity but chloroform and methanolic extracts showed promising antibacterial potency against Staphylococcus aureus, Sarcina lutea, Bacillus megaterium, Bacillus subtilis, Salmonella typhi and Shigella dysenteriae (leaf > root > stem). This activity was evaluated using disc diffusion method with a standard antibiotic, 30 µg/disc of amoxicillin. Conclusions: Strong antibacterial potency of chloroform and methanolic extracts provides new antibacterial compounds.

  6. Carbon Nanomaterials as Antibacterial Colloids

    OpenAIRE

    Michael Maas

    2016-01-01

    Carbon nanomaterials like graphene, carbon nanotubes, fullerenes and the various forms of diamond have attracted great attention for their vast potential regarding applications in electrical engineering and as biomaterials. The study of the antibacterial properties of carbon nanomaterials provides fundamental information on the possible toxicity and environmental impact of these materials. Furthermore, as a result of the increasing prevalence of resistant bacteria strains, the development of ...

  7. Natural antibacterial characteristics of honey

    OpenAIRE

    Pešić-Mikulec Dragana M.; Dugalić-Vrndić Nada; Baltić Milan Ž.

    2004-01-01

    Honey was used as a medicine in traditional medicine of the Ancient Times ever since the age of Hippocrates. Scientifically based investigations of the medicinal qualities of honey date back to the 19th century. There have been constant polemics, about the medicinal characteristics of honey and parameters that cause them, among scientists and apiculture experts. In this paper, we processed much data from literature, which indicate the antibacterial characteristics of honey through the experim...

  8. Nanomaterials for Defense Applications

    Science.gov (United States)

    Turaga, Uday; Singh, Vinitkumar; Lalagiri, Muralidhar; Kiekens, Paul; Ramkumar, Seshadri S.

    Nanotechnology has found a number of applications in electronics and healthcare. Within the textile field, applications of nanotechnology have been limited to filters, protective liners for chemical and biological clothing and nanocoatings. This chapter presents an overview of the applications of nanomaterials such as nanofibers and nanoparticles that are of use to military and industrial sectors. An effort has been made to categorize nanofibers based on the method of production. This chapter particularly focuses on a few latest developments that have taken place with regard to the application of nanomaterials such as metal oxides in the defense arena.

  9. Phenomenon of Psychological Defense

    Directory of Open Access Journals (Sweden)

    Elena T. Sokolova

    2011-01-01

    Full Text Available The author discusses the controversial issues of formation and functioning of psy¬chological defense mechanisms in ontogenesis and in personality disorders as they are represented in classical and contemporary psychoanalysis, in cognitivism and communication theory. The paper emphasizes the role of cognitive organi¬zation (style, sign-symbolic mediation, representative system of object relations and attachments in individual typological variability of the level organization of ciency of personal and social adaptation, in maturity and mental health of personality

  10. Antibacterial and Antifungal Compounds from Marine Fungi

    OpenAIRE

    Lijian Xu; Wei Meng; Cong Cao; Jian Wang; Wenjun Shan; Qinggui Wang

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review.

  11. Lysozyme-Based Antibacterial Nanomotors.

    Science.gov (United States)

    Kiristi, Melek; Singh, Virendra V; Esteban-Fernández de Ávila, Berta; Uygun, Murat; Soto, Fernando; Aktaş Uygun, Deniz; Wang, Joseph

    2015-09-22

    An effective and rapid bacterial killing nanotechnology strategy based on lysozyme-modified fuel-free nanomotors is demonstrated. The efficient antibacterial property of lysozyme, associated with the cleavage of glycosidic bonds of peptidoglycans present in the bacteria cell wall, has been combined with ultrasound (US)-propelled porous gold nanowire (p-AuNW) motors as biocompatible dynamic bacteria nanofighters. Coupling the antibacterial activity of the enzyme with the rapid movement of these p-AuNWs, along with the corresponding fluid dynamics, promotes enzyme-bacteria interactions and prevents surface aggregation of dead bacteria, resulting in a greatly enhanced bacteria-killing capability. The large active surface area of these nanoporous motors offers a significantly higher enzyme loading capacity compared to nonporous AuNWs, which results in a higher antimicrobial activity against Gram-positive and Gram-negative bacteria. Detailed characterization studies and control experiments provide useful insights into the underlying factors controlling the antibacterial performance of the new dynamic bacteria nanofighters. Rapid and effective killing of the Gram-positive Micrococcus lysodeikticus bacteria (69-84% within 1-5 min) is demonstrated. PMID:26308491

  12. DEFENSE PROGRAMS RISK MANAGEMENT FRAMEWORK

    Directory of Open Access Journals (Sweden)

    Constantin PREDA

    2012-01-01

    Full Text Available For the past years defense programs have faced delays in delivering defense capabilities and budget overruns. Stakeholders are looking for ways to improve program management and the decision making process given the very fluid and uncertain economic and political environment. Consequently, they have increasingly resorted to risk management as the main management tool for achieving defense programs objectives and for delivering the defense capabilities strongly needed for the soldiers on the ground on time and within limited defense budgets. Following a risk management based decision-making approach the stakeholders are expected not only to protect program objectives against a wide range of risks but, at the same time, to take advantage of the opportunities to increase the likelihood of program success. The prerequisite for making risk management the main tool for achieving defense programs objectives is the design and implementation of a strong risk management framework as a foundation providing an efficient and effective application of the best risk management practices. The aim of this paper is to examine the risk management framework for defense programs based on the ISO 31000:2009 standard, best risk management practices and the defense programs’ needs and particularities. For the purposes of this article, the term of defense programs refers to joint defense programs.

  13. Response Characteristics of Physiological Defense Indexes of Host Plant at Early Stage of Arbuscular Mycorrhiza Development between Amorpha fruticosa and AM Fungi%AM真菌和紫穗槐苗互作早期宿主防御生理指标的响应特征

    Institute of Scientific and Technical Information of China (English)

    宋鸽; 宋福强

    2011-01-01

    在温室盆栽条件下研究AM真菌与紫穗槐互作早期宿主防御生理指标的响应特征.结果表明:在AM真菌侵染宿主植物早期阶段,根系保护酶瞬时激活,植保素类黄酮瞬时积累,而且接种根内球囊霉( GI)同接种摩西球囊霉(GM)处理相比保护酶活性和类黄酮含量变化相对较大.接种AM真菌处理MDA含量下降,尤其在紫穗槐出苗后25天,接种GI和GM处理MDA含量分别降低26.6%和25.8%.在保护酶失活的同时,几丁质诱导子降解产物GlcN和可溶性蛋白含量增加,而且产生一些新的蛋白,由此推测:几丁质诱导子的降解和新增蛋白的出现是调节植物防御反应允许建立互惠共生体的可能机制.%This article studied the response characteristics of protective enzymes and malondialdehyde (MDA) at the early stage of the development of arbuscular mycorrhizal between AM fungi and Amorpha fruticosa with a potting experiment in a greenhouse. The result showed that at the early stage of A. Fruticosa infected with AM fungi, protective enzymes (PPO and POD) of the root system were transiently activated, along with an accumulation of flavonoid (a kind of phytoalexin). The activities of protective enzymes and the flavonoid contents had greater increases in roots inoculated with Gl (Glomus intraradices) than GM (Glomus mosseae). Additionally, the contents of MDA decreased respectively 26. 6% and 25. 8% in CM- and GI- colonized plants in 25 d after the seed germination. With inactivation of the protective enzymes, contents of soluble protein and GlcN (Glucosamine) increased and some new proteins occurred, which indicated that the degradation of chitin and emergence of new proteins were potential mechanisms regulating the defense responses of host plants to develop mutually beneficial symbiosis.

  14. Antibacterial activity of Pseudoalteromonas in the coral holobiont.

    Science.gov (United States)

    Shnit-Orland, Maya; Sivan, Alex; Kushmaro, Ariel

    2012-11-01

    Corals harbor diverse and abundant prokaryotic populations. Bacterial communities residing in the coral mucus layer may be either pathogenic or symbiotic. Some species may produce antibiotics as a method of controlling populations of competing microbial species. The present study characterizes cultivable Pseudoalteromonas sp. isolated from the mucus layer of different coral species from the northern Gulf of Eilat, Red Sea, Israel. Six mucus-associated Pseudoalteromonas spp. obtained from different coral species were screened for antibacterial activity against 23 tester strains. Five of the six Pseudoalteromonas strains demonstrated extracellular antibacterial activity against Gram-positive-but not Gram-negative-tester strains. Active substances secreted into the cell-free supernatant are heat-tolerant and inhibit growth of Bacillus cereus, Staphylococcus aureus, and of ten endogenous Gram-positive marine bacteria isolated from corals. The Pseudoalteromonas spp. isolated from Red sea corals aligned in a phylogenetic tree with previously isolated Pseudoalteromonas spp. of marine origin that demonstrated antimicrobial activity. These results suggest that coral mucus-associated Pseudoalteromonas may play a protective role in the coral holobiont's defense against potential Gram-positive coral pathogens. PMID:22767125

  15. Patterns of Oligonucleotide Sequences in Viral and Host Cell RNA Identify Mediators of the Host Innate Immune System

    NARCIS (Netherlands)

    Greenbaum, Benjamin D.; Rabadan, Raul; Levine, Arnold J.

    2009-01-01

    The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate responses generate selection forces acting both in pathogens and hosts that further determine their co-evol

  16. Commentary—Defensive Marketing Strategies

    OpenAIRE

    John R. Hauser; Steven M. Shugan

    2008-01-01

    For every new product and service entrant, there are usually many incumbents who must defend their positions in the market. Hence, defensive strategy is as least as critical as new-product strategy. Our 1983 article argued that defensive strategy critically depends on the distribution of buyer preferences and the position of the new entrant relative to the position of the incumbent in a multidimensional attribute space. Since the appearance of our 1983 article in , research in defensive strat...

  17. Plant Defense against Insect Herbivores

    OpenAIRE

    Søren Bak; Joel Fürstenberg-Hägg; Mika Zagrobelny

    2013-01-01

    Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged...

  18. Plant defense against insect herbivores

    DEFF Research Database (Denmark)

    Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

    2013-01-01

    , defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce...... defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects...

  19. What makes a natural clay antibacterial?

    Science.gov (United States)

    Williams, Lynda B.; Metge, David W.; Eberl, Dennis D.; Harvey, Ronald W.; Turner, Amanda G.; Prapaipong, Panjai; Port-Peterson, Amisha T.

    2011-01-01

    Natural clays have been used in ancient and modern medicine, but the mechanism(s) that make certain clays lethal against bacterial pathogens has not been identified. We have compared the depositional environments, mineralogies, and chemistries of clays that exhibit antibacterial effects on a broad spectrum of human pathogens including antibiotic resistant strains. Natural antibacterial clays contain nanoscale (2+ solubility.

  20. Evaluation of quinolone antibacterial consumption

    Directory of Open Access Journals (Sweden)

    E. P. Bernaz

    2016-08-01

    Full Text Available Quinolones are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected and as first-line therapy is recommended. To determine the place, compare and analyze the use of quinolone antibacterial in the most important departments of EMI during 2009 to 2014 and to assess their results for improvement of patients treatment quality was designed this study. In the evaluated period consumption of quinolone antibacterial in EMI recorded a decline from 91 to 46 DDD/1000 or by 49.45%, in IC departaments from 338.6 to 132.07 or by 61%, and vice versa in SSOT departments an increase from 41.28 to 57.59 DDD/1000 or by 31.51%. Medium annual consumption in all institution recorded 63.03 DDD/1000, respectvely 174.90 in IC and 45.10 in SSOT departments. In 2014 IC departments recorded 2439.8 lei per DDD/1000, that was 8.72 times more than cost of 279.9 lei in SSOT departments and 7.51 times than 324.96 lei per DDD/1000 in all EMI. The yearly medium in EMI is around the same with all other international hospitals of 66.13 DDD/1000 and by 27.23% higher than 49.54 DDD/1000 recorded in large acute Australian public hospitals. The obtained results will be an important data for optimization in planning annual hospital necessities and rational antimicrobial prescribing as well as suggest the idea for expansion development and support antimicrobial stewardship initiatives.

  1. Antibacterial activity of selected Myanmar medicinal plants

    International Nuclear Information System (INIS)

    Thirteen plants which are traditionally used for the treatment of dysentery and diarrhoea in Myanmar were selected and tested for antibacterial activity by using agar disc diffusion technique. Polar and nonpolar solvents were employed for extraction of plants. The minimum inhibitory concentration (MIC) of the extracts with the most significant predominant activity were evaluated by plate dilution method. The plants Eugenia jambolana, Quisqualis indica, Leucaena glauca and Euphorbia splendens var. 1 were found to show significant antibacterial activity. It was also observed that extracts using nonpolar solvents did not show any antibacterial activity and extracts using polar solvents showed antibacterial activity on tested bacteria, indicating that the active chemical compound responsible for the antibacterial action must be a polar soluble compound. (author)

  2. 抗菌肽作用机制的研究进展%Advances on Action Mechanism of Antibacterial Peptides

    Institute of Scientific and Technical Information of China (English)

    刘立伟; 邓磊

    2012-01-01

    As the important defense substance in innate immune system, the antibacterial peptides have the strong bactericidal properties. To review the several mechanisms of antimicrobial peptides.%抗菌肽是宿主防御系统的重要成分,具有强烈的杀菌特性。综述了抗菌肽的几种作用机制。

  3. Antibacterial Activity of Silicate Bioceramics

    Institute of Scientific and Technical Information of China (English)

    HU Sheng; NING Congqin; ZHOU Yue; CHEN Lei; LIN Kaili; CHANG Jiang

    2011-01-01

    Four kinds of pure silicate ceramic particles, CaSiO3, Ca3SiO5, bredigite and akermanite were prepared and their bactericidal effects were systematically investigated. The phase compositions of these silicate ceramics were characterized by XRD. The ionic concentration meas urement revealed that the Calcium (Ca) ion concentration were relatively higher in Ca3SiO5 and bredigite, and much lower in CaSiO3 and akermanite. Accordingly, the pH values of the four silicate ceramics extracts showed a positive correlation with the particle concentrations. Meanwhile, by decreasing the particle size, higher Ca ion concentrations can be achieved, leading to the increase of aqueous pH value as well. In summary, all of the four silicate ceramics tested in our study showed antibacterial effect in a dose-dependent manner. Generally, the order of their antibacterial activity against E.coli from strong to weak is Ca3SiO5, bredigite, CaSiO3 and akermanite.

  4. Quaternary Ammonium Polyethyleneimine: Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Ira Yudovin-Farber

    2010-01-01

    Full Text Available Quaternary ammonium polyethyleneimine- (QA-PEI- based nanoparticles were synthesized using two synthetic methods, reductive amination and N-alkylation. According to the first method, QA-PEI nanoparticles were synthesized by cross-linking with glutaraldehyde followed by reductive amination with octanal and further N-methylation with methyl iodide. The second method is based on crosslinking with dialkyl halide followed by N-alkylation with octyl halide and further N-methylation with methyl iodide. QA-PEI nanoparticles completely inhibited bacterial growth (>106 bacteria, including both Gram-positive, that is, Staphylococcus aureus at 80 g/mL, and Gram-negative, that is, Escherichia coli at 320 g/mL. Activity analysis revealed that the degree of alkylation and N-methylation of the QA-PEI nanoparticles plays a significant role in antibacterial activity of the reagent. The most potent compound was octyl alkylated QA-PEI alkylated at 1 : 1 mole ratio (primary amine of PEI monomer units/alkylating agent. Also, cytotoxicity studies on MAT-LyLu and MBT cell lines were performed with QA-PEI nanoparticles. These findings confirm previous reports that polycations bearing quaternary ammonium moieties inhibit bacterial growth in vitro and have a potential use as additives in medical devices which need antibacterial properties.

  5. Technical Soddi Defenses: The Trojan Horse Defense Revisited

    OpenAIRE

    Chad Steel

    2014-01-01

    In 2004, the Trojan horse defense was at a crossroads, with two child pornography cases where it was successfully employed in the United Kingdom, resulting in acquittals.  The original Trojan horse defense has now become part of the more general “technical SODDI” defense, which includes the possibility of unknown actors using unsecured Wi-Fi connections or having physical access to a computer to perform criminal acts.  In the past ten years, it has failed to be effective in the United States ...

  6. MAIN FACTORS IN PREPARATION OF ANTIBACTERIAL PARTICLES/PVC COMPOSITE

    Institute of Scientific and Technical Information of China (English)

    Xuehua Chen; Chunzhong Li; Ling Zhang; Shoufang Xu; Qiuling Zhou; Yihua Zhu; Xianzhang Qu

    2004-01-01

    Zirconium phosphate containing silver was chosen as antibacterial particles in preparing antibacterial particles/PVC composite. The effect of surface property of the antibacterial particles and of their filler content on the properties of antibacterial particles/PVC composite was studied. The effect of the interfacial compatibility on mechanical properties of the composite was also discussed. Experimental results showed that the antibacterial PVC composite had good antibacterial property, reaching almost 100% bacteriostatic level at an antibacterial powder filler content of 1.5 phr.

  7. Induction, selection and antibacterial activity of the antibacterial peptides from lepldopteran insect cultured cell lines

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    We induced 3 cell lines that were in vitro cultured from Lepidoptera with heat inactivated Escherichia coil DH5α to stimulate the antibacterial peptide followed by antibacterial activity assay,induction dynamic research and Tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Tricine SDS-PAGE) experiment.The antibacterial activity of the induced BTI-Tn-5B1 cell line was the highest,and the antibacterial activity increased gradually to the highest level in 16 hours after stimulation.A new antibacterial peptide with a molecular weight of about 8000 Da was preferentially induced in Trichoplusia ni BTI-Tn-5B1 ceils in 16 hours after stimulation.Antibacterial activity assays indicated that it had inhibition against Staphylococcus aureus,Escherichia coli K12D31 and Salmonella derby.It has especially strong inhibition against Gram-negative bacteria such as Escherichia coli KI2D31 and Salmonella derby.

  8. Antibacterial Resistance in African Catfish Aquaculture: a Review

    OpenAIRE

    Madubuike U. ANYANWU; Kennedy F. Chah

    2016-01-01

    Antibacterial resistance (AR) is currently one of the greatest threats to mankind as it constitutes health crisis. Extensive use of antibacterial agents in human and veterinary medicine, and farm crops have resulted in emergence of antibacterial-resistant organisms in different environmental settings including aquaculture. Antibacterial resistance in aquaculture is a serious global concern because antibacterial resistance genes (ARGs) can be transferred easily from aquaculture setting to othe...

  9. Antibacterial phenylpropanoid glycosides from Paulownia tomentosa Steud.

    Science.gov (United States)

    Kang, K H; Jang, S K; Kim, B K; Park, M K

    1994-12-01

    The butanol extract of Paulownia tomentosa stem showed antibacterial activity against Staphylococcus aureus (SG511, 285 and 503), Streptococcus pyogenes (A308 and A77) and Streptococcus faecium MD8b etc. The most active compound of the extract was identified to be campneoside I, which had a minimal inhibitory concentration (MIC) of 150 micrograms/ml against Streptococcus and Staphylococcus species. From such antibacterial activity, the methoxy group of campneoside I was postulated to be the essential element for the antibacterial activity. PMID:10319161

  10. Antibacterial Effect of the Conducting Polyaniline

    Institute of Scientific and Technical Information of China (English)

    Nanlin SHI; Xuemei GUO; Hemin JING; Jun GONG; Chao SUN; Ke YANG

    2006-01-01

    Excellent antibacterial performance of polyaniline (Pani) against Escherichia coli and Gram-positive Staphylococcus aureus microorganisms has been demonstrated under both dark and visible light conditions. The electrostatic adherence between the Pani molecules and the bacteria may play a very important role for the antibacterial reaction of the Pani. As a result of our investigation, conducting Pani and its composites/blends are believed to be useful as a new type of antibacterial agent, self-clean as well as multifunctional material for improving the human health and living environment.

  11. Construction of a Metagenomic DNA Library of Sponge Symbionts and Screening of Antibacterial Metabolites

    Institute of Scientific and Technical Information of China (English)

    CHEN Juan; ZHU Tianjiao; LI Dehai; CUI Chengbin; FANG Yuchun; LIU Hongbing; LIU Peipei; GU Qianqun; ZHU Weiming

    2006-01-01

    To study the bioactive metabolites produced by sponge-derived uncultured symbionts, a metagenomic DNA library of the symbionts of sponge Gelliodes gracilis was constructed. The average size of DNA inserts in the library was 20 kb. This library was screened for antibiotic activity using paper disc assaying. Two clones displayed the antibacterial activity against Micrococcus tetragenus. The metabolites of these two clones were analyzed through HPLC. The result showed that their metabolites were quite different from those of the host E. coli DH5α and the host containing vector pHZ132. This study may present a new approach to exploring bioactive metabolites of sponge symbionts.

  12. Arabidopsis defense response against Fusarium oxysporum.

    Science.gov (United States)

    Berrocal-Lobo, Marta; Molina, Antonio

    2008-03-01

    The plant fungal pathogen Fusarium oxysporum (Fox) is the causal agent of root rot or wilt diseases in several plant species, including crops such as tomato (Solanum lycopersicum), banana (Musa sapientum) and asparagus (Asparagus officinalis). Colonization of plants by Fox leads to the necrosis of the infected tissues, a subsequent collapse of vascular vessels and decay of the plant. Plant resistance to Fox appears to be monogenic or oligogenic depending on the host. Perception of Fox by plants follows the concept of elicitor-induced immune response, which in turn activates several plant defense signaling pathways. Here, we review the Fox-derived elicitors identified so far and the interaction among the different signaling pathways mediating plant resistance to Fox. PMID:18289920

  13. Molecular strategies of plant defense and insect counter-defense

    Institute of Scientific and Technical Information of China (English)

    KEYANZHU-SALZMAN; JIAN-LONGBI; TONG-XIANLIU

    2005-01-01

    The prediction of human population growth worldwide indicates there will be a need to substantially increase food production in order to meet the demand on food supply.This can be achieved in part by the effective management of insect pests. Since plants have co-evolved with herbivorous insects for millions of years, they have developed an array of defense genes to protect themselves against a wide variety of chewing and sucking insects.Using these naturally-occurring genes via genetic engineering represents an environmentally friendly insect pest-control measure. Insects, however, have been actively evolving adaptive mechanisms to evade natural plant defenses. Such evolved adaptability undoubtedly has helped insects during the last century to rapidly overcome a great many humanimposed management practices and agents, including chemical insecticides and genetically engineered plants. Thus, better understanding of the molecular and genetic basis of plant defense and insect counter-defense mechanisms is imperative, not only from a basic science perspective, but also for biotechnology-based pest control practice. In this review, we emphasize the recent advance and understanding of molecular strategies of attack-counterattack and defense-counter-defense between plants and their herbivores.

  14. Antibacterial activity of Parmelia perlata

    Institute of Scientific and Technical Information of China (English)

    Alwar Vidyalakshmi; Kandaswamy Kruthika

    2012-01-01

    Objective: To test efficacy of Parmelia perlata (P. perlata), which is used in traditional medicine for rapid wound healing against test bacteria that cause wound infections. Methods: Different solvents such as methanol, ethyl acetate and acetone were used for extraction of P. perlata. The sensitivity of the test bacteria to solvent extracts of P. perlata was tested by measuring the zone of inhibition on growth media and by determining the minimal inhibitory concentration and minimal bactericidal concentration. Results: Methanol, ethyl acetate and acetone extracts of P.perlata have shown inhibitory activity against Staphylococcus aureus (S.aureus). Conclusions: The results of the present study indicate that P. perlata has potential antibacterial compounds againstS.aureus that causes multitude of skin infections among human beings. Development of drugs from natural compounds can help us to combat antibiotic-resistant bacteria.

  15. Optical control of antibacterial activity

    Science.gov (United States)

    Velema, Willem A.; van der Berg, Jan Pieter; Hansen, Mickel J.; Szymanski, Wiktor; Driessen, Arnold J. M.; Feringa, Ben L.

    2013-11-01

    Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism.

  16. Defense Meteorological Satellite Program (DMSP)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Defense Meteorological Satellite Program (DMSP) satellites collect visible and infrared cloud imagery as well as monitoring the atmospheric, oceanographic,...

  17. Epigenetic Control of Defense Signaling and Priming in Plants

    Science.gov (United States)

    Espinas, Nino A.; Saze, Hidetoshi; Saijo, Yusuke

    2016-01-01

    Immune recognition of pathogen-associated molecular patterns or effectors leads to defense activation at the pathogen challenged sites. This is followed by systemic defense activation at distant non-challenged sites, termed systemic acquired resistance (SAR). These inducible defenses are accompanied by extensive transcriptional reprogramming of defense-related genes. SAR is associated with priming, in which a subset of these genes is kept at a poised state to facilitate subsequent transcriptional regulation. Transgenerational inheritance of defense-related priming in plants indicates the stability of such primed states. Recent studies have revealed the importance and dynamic engagement of epigenetic mechanisms, such as DNA methylation and histone modifications that are closely linked to chromatin reconfiguration, in plant adaptation to different biotic stresses. Herein we review current knowledge regarding the biological significance and underlying mechanisms of epigenetic control for immune responses in plants. We also argue for the importance of host transposable elements as critical regulators of interactions in the evolutionary “arms race” between plants and pathogens. PMID:27563304

  18. Epigenetic control of defense signaling and priming in plants

    Directory of Open Access Journals (Sweden)

    Nino Asuela Espinas

    2016-08-01

    Full Text Available Immune recognition of pathogen-associated molecular patterns or effectors leads to defense activation at the pathogen challenged sites. This is followed by systemic defense activation at distant non-challenged sites, termed systemic acquired resistance (SAR. These inducible defenses are accompanied by extensive transcriptional reprogramming of defense-related genes. SAR is associated with priming, in which a subset of these genes is kept at a poised state to facilitate subsequent transcriptional regulation. Transgenerational inheritance of defense-related priming in plants indicates the stability of such primed states. Recent studies have revealed the importance and dynamic engagement of epigenetic mechanisms, such as DNA methylation and histone modifications that are closely linked to chromatin reconfiguration, in plant adaptation to different biotic stresses. Herein we review current knowledge regarding the biological significance and underlying mechanisms of epigenetic control for immune responses in plants. We also argue for the importance of host transposable elements (TEs as critical regulators of interactions in the evolutionary arms race between plants and pathogens.

  19. Dendritic nanocomposite for delivery of antibacterial agent

    Institute of Scientific and Technical Information of China (English)

    Pureti Madhu Kumar; PSrinivasa Babu; Shaik Rasheed; Ramadoss Karthikeyan

    2013-01-01

    Objective: To develop and explore the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti bacterial bioactive, Trimethoprim. Methods: For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Trimethoprim and targeted to the resistant producing strains of both gram positive and gram negative. The antibacterial activity was carried out by agar well-diffusion method to compare zone of inhibition with standard drug and plain PPI dendrimer. Results: The study showed that the Trimethoprim loaded dendrimer has significant antibacterial activity than the plain PPI dendrimer, but standard drug was not shown zone of inhibition upon both microorganisms butKlebsiella pneumoniae (K. pneumoniae) the pure drug showed activity. Conclusions: In this study antibacterial activity of synthesized system is also relatively safer and holds potential to deliver any other antibacterial agent to the resistant producing strains.

  20. Two New Antibacterial Iridoids from Patrinia rupestris

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Two new iridoids (1 and 2) were isolated from the roots of Patrinia rupestris (Pall.) Juss.Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited strong antibacterial activities against Eschecichia coli and Staphylococcus aureus, respectively.

  1. Antibacterial phenolics from the mangrove Lumnitzera racemosa

    Digital Repository Service at National Institute of Oceanography (India)

    DeSouza, L.; Wahidullah, S.; PrabhaDevi

    ether (3→8″)quercetin –3O-rhamnoside 8] from the mangrove plant, L. racemosa22. Quercetin besides being antibacterial is an effective antioxidant. Its glycosidic form should also be equally effective since in biological system glycosides undergo... enzymatic hydrolysis to the corresponding aglycone23 and thus contribute to some extent to the observed antibacterial activity. A variety of biological activities for biflavonoids have been published including anti inflammatory, antimicrobial, anti-oxidants...

  2. Antibacterial activity of mushroom Osmoporus odoratus

    Directory of Open Access Journals (Sweden)

    Sivakumar R

    2006-01-01

    Full Text Available The petroleum ether, chloroform, acetone and water extracts of mushroom Osmoporus odoratus were selected for examine the antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa by disc diffusion method using Muller Hinton agar media. And the extracts were compared with that of standard ampicillin (30 µg and chloramphenicol (30 µg. The water extract alone showed antibacterial activity against the tested organisms and the results were comparable with that of ampicillin rather than chloramphenicol.

  3. Antibacterial activity of selected glass ionomer cements

    Directory of Open Access Journals (Sweden)

    Elżbieta Łuczaj-Cepowicz

    2014-01-01

    Full Text Available Introduction: The aim of the paper was to determine the antibacterial activity of four glass ionomer cements against bacteria of the genera Streptococcus and Lactobacillus. Material and methods: Four capsulated glass ionomer cements were applied in the study: Fuji Triage (GC, Fuji IX (GC, Ketac Molar (3M Espe and Ketac Silver (3M Espe. Four standard bacterial strains were used to assess the antibacterial activity of the studied cements: Streptococcus mutans, S. sanguis, S. salivarius and Lactobacillus casei. The antibacterial activity was determined by the agar diffusion method. The bacterial suspension was spread with a cotton swab on TSA plates. For each material six wells (7 mm diameter, 5 mm deep were made with a cork borer. Each well was then filled with freshly prepared cements. The results were obtained by measuring the bacterial growth inhibition zone after 1, 2, 3 and 7 days. Results: Fuji Triage cement inhibited the growth of all bacterial strains. Fuji IX cement demonstrated the most potent antibacterial activity against S. sanguis. Ketac Molar showed antibacterial activity against S. sanguis and S. salivarius, whereas Ketac Silver was efficient against S. mutans as well. Neither of the Ketac cements inhibited growth of the standard L. casei strain. Discussion: Antibacterial activity of glass ionomer cements has attracted the interest of scientists in recent years. Most authors, including us, carried out experiments using the agar diffusion method and demonstrated antibacterial activity of glass ionomer cements. Different antibacterial activity of glass ionomer cements, observed in our study and studies of other authors, depended on the evaluated cement, bacterial strain and period of evaluation.

  4. Antibacterial activity of polyphenols of Garcinia indica

    OpenAIRE

    Lakshmi, C.; K Akshaya Kumar; T J Dennis; T. S. S. P. N. S. Sanath Kumar

    2011-01-01

    The aim of present work is to study the antibacterial activity of polyphenols isolated from the ethyl acetate soluble of methanol extract of stem bark of Garcinia indica against Staphylococcus aureus, Salmonella typhi and Escherichia coli by paper disc method. The results showed good antibacterial activity against S. aureus at higher concentrations, moderate at lower concentrations, against S. typhi moderate at higher concentrations but no activity against E. coli even at higher concentration...

  5. Antibacterial Activity of Polyphenols of Garcinia Indica

    OpenAIRE

    Lakshmi, C.; Kumar, K. Akshaya; T J Dennis; Kumar, T. S. S. P. N. S. Sanath

    2011-01-01

    The aim of present work is to study the antibacterial activity of polyphenols isolated from the ethyl acetate soluble of methanol extract of stem bark of Garcinia indica against Staphylococcus aureus, Salmonella typhi and Escherichia coli by paper disc method. The results showed good antibacterial activity against S. aureus at higher concentrations, moderate at lower concentrations, against S. typhi moderate at higher concentrations but no activity against E. coli even at higher concentration...

  6. Copper-polymer nanocomposites: An excellent and cost-effective biocide for use on antibacterial surfaces.

    Science.gov (United States)

    Tamayo, Laura; Azócar, Manuel; Kogan, Marcelo; Riveros, Ana; Páez, Maritza

    2016-12-01

    The development of polymer nanocomposites with antimicrobial properties has been a key factor for controlling or inhibiting the growth of microorganisms and preventing foodborne diseases and nosocomial infections. Commercially available antibacterial products based on silver-polymer are the most widely used despite the fact that copper is considerably less expensive. The incorporation of copper nanoparticles as antibacterial agents in polymeric matrices to generate copper-polymer nanocomposites have presented excellent results in inhibiting the growth of a broad spectrum of microorganisms. The potential applications in food packaging, medical devices, textiles and pharmaceuticals and water treatment have generated an increasing number of investigations on preparing copper based nanocomposites and alternative polymeric matrices, as potential hosts of nano-modifiers. This review presents a comprehensive compilation of previous published work on the subject, mainly related to the antimicrobial activity of copper polymer nanocomposites. Within all the phenomenology associated to antibacterial effects we highlight the possible mechanisms of action. We discuss the differences in the susceptibility of Gram negative and positive bacteria to the antibacterial activity of nanocomposites, and influencing factors. As well, the main applications of copper polymer-metal nanocomposites are described, considering their physical and chemical characteristics. Finally, some commercially available copper-polymer nanocomposites are described. PMID:27612841

  7. Technical Soddi Defenses: The Trojan Horse Defense Revisited

    Directory of Open Access Journals (Sweden)

    Chad Steel

    2014-12-01

    Full Text Available In 2004, the Trojan horse defense was at a crossroads, with two child pornography cases where it was successfully employed in the United Kingdom, resulting in acquittals.  The original Trojan horse defense has now become part of the more general “technical SODDI” defense, which includes the possibility of unknown actors using unsecured Wi-Fi connections or having physical access to a computer to perform criminal acts.  In the past ten years, it has failed to be effective in the United States for criminal cases, with no published acquittals in cases where it was the primary defense.  In the criminal cases where it has been used as leverage in plea negotiations, there has been either poor forensics performed by the prosecution or political pressure to resolve a matter.  On the civil side, however, the defense has been wildly successful, effectively shutting down large John Doe copyright infringement litigation against non-commercial violators.  

  8. Proteomic Characterization of Host Response to Yersinia pestis

    Energy Technology Data Exchange (ETDEWEB)

    Chromy, B; Perkins, J; Heidbrink, J; Gonzales, A; Murhpy, G; Fitch, J P; McCutchen-Maloney, S

    2004-05-11

    Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.

  9. Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide. [Staphylococcus aureus; Proteus mirabilis; Pasteurella pneumotropica

    Energy Technology Data Exchange (ETDEWEB)

    Jakab, G.J.

    1987-02-01

    The effect of acute exposures to NO/sub 2/ on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. With S. aureus pulmonary antibacterial defenses were suppressed at NO/sub 2/ levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO/sub 2/ exposure prior to bacterial challenge) raised the threshold concentration for NO/sub 2/-induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO/sub 2/ did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with /sup 32/P-labeled staphylococci.

  10. The Role of Hyaluronan in Innate Defense Responses of the Intestine

    OpenAIRE

    de la Motte, Carol A; Sean P Kessler

    2015-01-01

    Hyaluronan is an abundant extracellular matrix component prevalent in the vertebrate intestinal tract. Here we discuss what is known about hyaluronan distribution during homeostasis and inflammatory diseases of the gut and discuss ways in which this glycosaminoglycan can participate in regulating innate host defense mechanisms. These natural responses include mechanisms promoting rapid leukocyte recruitment after bacterial challenge/colon tissue damage as well as promoting epithelial defense ...

  11. Alveolar macrophages and lung surfactant in the defense against Cryptococcus neoformans

    OpenAIRE

    Gross, Norma Teresa

    2000-01-01

    Cryptococcus neoformans causes disease mainly in immunosuppressed patients, especially those with AIDS, and on corticosteroids. The yeast is normally inhaled and the lung is the primary site of infection, where the alveolar macrophages (AM) provide a first line of host defense. The aim of this thesis was to study immune responses of AM and immunomodulatory functions of lung surfactant phospholipids in the defense against C. neoformans, using the rat or rabbit as animal model...

  12. ROS signaling, phytohormone signaling and toxin tolerance: defense mechanisms in Arabidopsis thaliana against Botrytis cinerea

    OpenAIRE

    Cui, Fuqiang

    2014-01-01

    To face the constant challenges from numerous pathogens in the environment, sophisticated defense systems have evolved in plants. Reactive oxygen species (ROS) and phytohormones are important cellular compounds that regulate plant defense systems to overcome biotic stresses from different pathogens. Against biotrophic pathogens, which require living host cells, hypersensitive cell death response (HR), a type of programed cell death mediated by ROS and salicylic acid (SA), is effective for imm...

  13. The pathogen-actin connection: A platform for defense signaling in plants

    Energy Technology Data Exchange (ETDEWEB)

    Day, B; Henty, Jessica L; Porter, K J; Staiger, Chris J

    2011-09-08

    The cytoskeleton, a dynamic network of cytoplasmic polymers, plays a central role in numerous fundamental processes, such as development, reproduction, and cellular responses to biotic and abiotic stimuli. As a platform for innate immune responses in mammalian cells, the actin cytoskeleton is a central component in the organization and activation of host defenses, including signaling and cellular repair. In plants, our understanding of the genetic and biochemical responses in both pathogen and host that are required for virulence and resistance has grown enormously. Additional advances in live-cell imaging of cytoskeletal dynamics have markedly altered our view of actin turnover in plants. In this review, we outline current knowledge of host resistance following pathogen perception, both in terms of the genetic interactions that mediate defense signaling, as well as the biochemical and cellular processes that are required for defense signaling.

  14. The coevolutionary implications of host tolerance.

    Science.gov (United States)

    Best, Alex; White, Andy; Boots, Mike

    2014-05-01

    Host tolerance to infectious disease, whereby hosts do not directly "fight" parasites but instead ameliorate the damage caused, is an important defense mechanism in both plants and animals. Because tolerance to parasite virulence may lead to higher prevalence of disease in a population, evolutionary theory tells us that while the spread of resistance genes will result in negative frequency dependence and the potential for diversification, the evolution of tolerance is instead likely to result in fixation. However, our understanding of the broader implications of tolerance is limited by a lack of fully coevolutionary theory. Here we examine the coevolution of tolerance across a comprehensive range of classic coevolutionary host-parasite frameworks, including equivalents of gene-for-gene and matching allele and evolutionary invasion models. Our models show that the coevolution of host tolerance and parasite virulence does not lead to the generation and maintenance of diversity through either static polymorphisms or through "Red-queen" cycles. Coevolution of tolerance may however lead to multiple stable states leading to sudden shifts in parasite impacts on host health. More broadly, we emphasize that tolerance may change host-parasite interactions from antagonistic to a form of "apparent commensalism," but may also lead to the evolution of parasites that are highly virulent in nontolerant hosts.

  15. Seaweed Polysaccharides and Derived Oligosaccharides Stimulate Defense Responses and Protection Against Pathogens in Plants

    Directory of Open Access Journals (Sweden)

    Alejandra Moenne

    2011-11-01

    Full Text Available Plants interact with the environment by sensing “non-self” molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA, jasmonic acid (JA and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i Pathogenesis-Related (PR proteins with antifungal and antibacterial activities; (ii defense enzymes such as pheylalanine ammonia lyase (PAL and lipoxygenase (LOX which determine accumulation of phenylpropanoid compounds (PPCs and oxylipins with antiviral, antifugal and antibacterial activities and iii enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants.

  16. Ancient host-pathogen associations maintained by specificity of chemotaxis and antibiosis.

    OpenAIRE

    Gerardo, Nicole M.; Jacobs, Sarah R.; Currie, Cameron R; Mueller, Ulrich G.

    2006-01-01

    Switching by parasites to novel hosts has profound effects on ecological and evolutionary disease dynamics. Switching requires that parasites are able to establish contact with novel hosts and to overcome host defenses. For most host–parasite associations, it is unclear as to what specific mechanisms prevent infection of novel hosts. Here, we show that parasitic fungal species in the genus Escovopsis, which attack and consume the fungi cultivated by fungus-growing ants, are attracted to their...

  17. Host stress hormones alter vector feeding preferences, success, and productivity.

    Science.gov (United States)

    Gervasi, Stephanie S; Burkett-Cadena, Nathan; Burgan, Sarah C; Schrey, Aaron W; Hassan, Hassan K; Unnasch, Thomas R; Martin, Lynn B

    2016-08-17

    Stress hormones might represent a key link between individual-level infection outcome, population-level parasite transmission, and zoonotic disease risk. Although the effects of stress on immunity are well known, stress hormones could also affect host-vector interactions via modification of host behaviours or vector-feeding patterns and subsequent reproductive success. Here, we experimentally manipulated songbird stress hormones and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors in addition to defensive behaviours of hosts. Despite being more defensive, birds with elevated stress hormone concentrations were approximately twice as likely to be fed on by mosquitoes compared to control birds. Moreover, stress hormones altered the relationship between the timing of laying and clutch size in blood-fed mosquitoes. Our results suggest that host stress could affect the transmission dynamics of vector-borne parasites via multiple pathways. PMID:27512147

  18. Trusted Hosts in Host Identity Protocol (HIP)

    OpenAIRE

    K.C., Amir

    2012-01-01

    The goal of the project was to study the possibilities to establish trusted hosts in Host Identity Protocol (HIP) and implement certificate handling in HIP packets. The time complexity and performance while using certificates in HIP packets was also measured. The research project was carried out at Arcada University of Applied Sciences in collaboration with Helsinki University. The project aimed to implement standard x.509 certification of the public key used as HI (Host Identity) to deri...

  19. Avoid, attack or do both? Behavioral and physiological adaptations in natural enemies faced with novel hosts

    Directory of Open Access Journals (Sweden)

    Brown Sam P

    2005-11-01

    Full Text Available Abstract Background Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation, neutralization of the defensive innovation (physiological adaptation or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii to study the factors that govern the relative investment in each adaptation mode. Results Our results show that (i a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When (i holds, we find that (ii the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. Conclusion Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties.

  20. Sustained Release of Antibacterial Lipopeptides from Biodegradable Polymers against Oral Pathogens.

    Science.gov (United States)

    Eckhard, Lea H; Houri-Haddad, Yael; Sol, Asaf; Zeharia, Rotem; Shai, Yechiel; Beyth, Shaul; Domb, Abraham J; Bachrach, Gilad; Beyth, Nurit

    2016-01-01

    The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer. PMID:27606830

  1. Sustained Release of Antibacterial Lipopeptides from Biodegradable Polymers against Oral Pathogens

    Science.gov (United States)

    Eckhard, Lea H.; Houri-Haddad, Yael; Sol, Asaf; Zeharia, Rotem; Shai, Yechiel; Beyth, Shaul; Domb, Abraham J.

    2016-01-01

    The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer. PMID:27606830

  2. 76 FR 53119 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-08-25

    ... of Availability (NOA) in the Federal Register (76 FR 28757) announcing the revised Defense Logistics... Office of the Secretary Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense....

  3. Factors affecting larval tick feeding success: host, density and time

    OpenAIRE

    Cami R Jones; Brunner, Jesse L.; Scoles, Glen A.; Jeb P Owen

    2015-01-01

    Background Ectoparasites rely on blood-feeding to sustain activity, support development and produce offspring. Blood-feeding is also a route for transmission of diverse vector-borne pathogens. The likelihood of successfully feeding is thus an important aspect of ectoparasite population dynamics and pathogen transmission. Factors that affect blood-feeding include ectoparasite density, host defenses, and ages of the host and ectoparasite. How these factors interact to affect feeding success is ...

  4. Are you my symbiont? Microbial polymorphic toxins and antimicrobial compounds as honest signals of beneficial symbiotic defensive traits.

    Science.gov (United States)

    Hillman, Kai; Goodrich-Blair, Heidi

    2016-06-01

    In defensive symbioses where microbes benefit their host by killing competitors, predators or parasites, natural selection should favor the transmission of microbes with the most beneficial defensive traits. During the initiation of symbiosis, the host's ability to accurately pre-assess a symbiont's beneficial traits would be a selective advantage. We propose that one mechanism by which a host could recognize and select a beneficial partner would be if the latter displayed an honest signal of its defensive or other symbiotic capabilities. As one example, we suggest that polymorphic toxins and their surface receptors, which are involved in inter-microbial competition and predator killing activities, can be honest signals that facilitate partner choice in defensive symbioses. PMID:27128187

  5. Antibacterial resistance: Current problems and possible solutions

    Directory of Open Access Journals (Sweden)

    Sharma Rashmi

    2005-03-01

    Full Text Available Antimicrobial resistance is a natural biological phenomenon of response of microbes to the selective pressure of an antimicrobial drug. Resistance may be inherent, which explains the phenomenon of opportunistic infection or acquired. Concern about the resistance increased in the late 1990′s and since then, many governmental and agency reports have been published regarding the agricultural use of antibacterials, advising less use of antibacterials, appropriate choice of antibacterials and regimens, prevention of cross-infection and development of new antibacterials. The emergence of multidrug resistant strains of Gram-negative bacteria (Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Salmonella species and Gram-positve organisms (Staphylococcus, Enterococcus, Streptococcus species is the more worrisome in the present therapeutic scenario. Multidrug - resistant tuberculosis is another serious public health problems. Resistance to some agents can be overcome by modifying the dosage regimens (e.g., using high-dose therapy or inhibiting the resistance mechanism (e.g., beta-lactamase inhibitors, whereas other mechanisms of resistance can only be overcome by using an agent from a different class. It is urgently required to ban the sale of antibiotics without prescription, to use antibiotics more judiciously in hospitals by intensive teaching of the principles of the use of antibiotics and to establish better control measures for nosocomial infections. Thus, it is highly recommended that practicing physicians should become aware of the magnitude of existing problem of antibacterial resistance and help in fighting this deadly threat by rational prescribing.

  6. Tunable, antibacterial activity of silicone polyether surfactants.

    Science.gov (United States)

    Khan, Madiha F; Zepeda-Velazquez, Laura; Brook, Michael A

    2015-08-01

    Silicone surfactants are used in a variety of applications, however, limited data is available on the relationship between surfactant structure and biological activity. A series of seven nonionic, silicone polyether surfactants with known structures was tested for in vitro antibacterial activity against Escherichia coli BL21. The compounds varied in their hydrophobic head, comprised of branched silicone structures with 3-10 siloxane linkages and, in two cases, phenyl substitution, and hydrophilic tail of 8-44 poly(ethylene glycol) units. The surfactants were tested at three concentrations: below, at, and above their Critical Micelle Concentrations (CMC) against 5 concentrations of E. coli BL21 in a three-step assay comprised of a 14-24h turbidometric screen, a live-dead stain and viable colony counts. The bacterial concentration had little effect on antibacterial activity. For most of the surfactants, antibacterial activity was higher at concentrations above the CMC. Surfactants with smaller silicone head groups had as much as 4 times the bioactivity of surfactants with larger groups, with the smallest hydrophobe exhibiting potency equivalent to sodium dodecyl sulfate (SDS). Smaller PEG chains were similarly associated with higher potency. These data link lower micelle stability and enhanced permeability of smaller silicone head groups to antibacterial activity. The results demonstrate that simple manipulation of nonionic silicone polyether structure leads to significant changes in antibacterial activity. PMID:26057244

  7. Toxicity and antibacterial assessment of chitosan-coated silver nanoparticles on human pathogens and macrophage cells

    Directory of Open Access Journals (Sweden)

    Jena P

    2012-04-01

    Full Text Available Prajna Jena1, Soumitra Mohanty1, Rojee Mallick1, Biju Jacob2, Avinash Sonawane11School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India; 2Center for Innovation, Technopark Technology Business Incubator, Bangalore, Karnataka, IndiaBackground: Pathogenic bacteria are able to develop various strategies to counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs have emerged as a potential alternative to conventional antibiotics because of their potent antimicrobial properties. The purpose of this study was to synthesize chitosan-stabilized AgNPs (CS-AgNPs and test for their cytotoxic, genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities.Methods: AgNPs were synthesized using chitosan as both a stabilizing and a reducing agent. Antibacterial activity was determined by colony-forming unit assay and scanning electron microscopy. Genotoxic and cytotoxic activity were determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide] assays. Cellular uptake and intracellular antibacterial activity were tested on macrophages.Results: CS-AgNPs exhibited potent antibacterial activity against different human pathogens and also impeded bacterial biofilm formation. Scanning electron microscopy analysis indicated that CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no significant cytotoxic or DNA damage effect on macrophages at the bactericidal dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs resulting in reduced intracellular bacterial survival in macrophages.Conclusion: The present study concludes that at a specific dose, chitosan-based AgNPs kill bacteria without harming the host cells, thus representing a potential template for the design of antibacterial agents to decrease bacterial colonization and to overcome the problem of drug resistance.Keywords: chitosan-silver nanoparticles, antibiofilm, cytotoxicity

  8. MgO nanoparticles as antibacterial agent: preparation and activity

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhen-Xing, E-mail: tangzhenxing@126.com [Department of Food Science, Anqing, Vocational and Technical College, Anqing, Anhui (China); Lv, Bin-Feng [Date Palm Research Center, King Faisal University, (Saudi Arabia)

    2014-07-15

    Bacterial pollution is a great risk for human health. Nanotechnology offers a way to develop new inorganic antibacterial agents. Nano-inorganic metal oxide has a potential to reduce bacterial contamination. MgO is an important inorganic oxide and has been widely used in many fields. Many studies have shown that MgO nanoparticles have good antibacterial activity. Therefore, in this paper, the main synthesis methods, antibacterial activity and antibacterial mechanisms of MgO nanoparticles are reviewed. (author)

  9. [Tuberculosis in compromised hosts].

    Science.gov (United States)

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  10. Effective antibacterials: at what cost? The economics of antibacterial resistance and its control.

    Science.gov (United States)

    White, Anthony R

    2011-09-01

    The original and successful business model of return on investment being sufficiently attractive to the pharmaceutical industry to encourage development of new antibacterial molecules and related diagnostics has been compromised by increasing development costs and regulatory hurdles, resulting in a decreasing chance of success and financial return. The supply of new effective agents is diminishing along with the number of companies engaged in antibacterial research and development. The BSAC Working Party on The Urgent Need:Regenerating Antibacterial Drug Discovery and Development identified the need to establish, communicate and apply the true health and economic value of antibacterials, along with the adoption of meaningful incentives, as part of the future model for antibacterial development. Robust data are needed on the cost of resistance and ineffective treatment of bacterial infection, along with national and local holistic analyses of the cost-benefit of antibacterials. An understanding of the true health and economic value of antibacterials and the cost of resistance across healthcare systems needs to be generated, communicated and used in order to set a pricing and reimbursement structure that is commensurate with value. The development and economic model of antibacterial use needs to be rebuilt based on this value through dialogue with the various stakeholders, including the pharmaceutical industry, and alternative incentives from 'push' to 'pull' and funding models, such as public/private partnerships, agreed. A research and development model that succeeds in developing and delivering new antibacterial agents that address the health needs of society from start to finish, 'from cradle to grave', must be established. PMID:21700625

  11. Soviet debate on missile defense

    Energy Technology Data Exchange (ETDEWEB)

    Parrott, B.

    1987-04-01

    Although the Strategic Defense Initiative (SDI) is meant to cope with the danger of a Soviet nuclear attack, the recent US debate over SDI has paid surprisingly little attention to Soviet views of ballistic missile defense. Despite the existence of a substantial body of pertinent scholarship, the debate has failed to take adequate account of major changes in Soviet ballistic missile defense policy since the mid-1960s. It has also neglected the links between current Soviet military policy and broader Soviet political and economic choices. The Soviets regard SDI not as a novel undertaking to reduce the risks of nuclear war but as an extension of the geopolitical competition between the superpowers. This competition has been dominated in the 1980s, in the Soviet view, by sharply increased US assertiveness and the decline of detente. Viewing SDI as a manifestation of these general trends, Soviet decision makers find the prospect of an unregulated race in ballistic missile defenses and military space technologies deeply unsettling. The deterioration of superpower relations has raised serious doubts in Moscow about the wisdom of Soviet external policy during the 1970s and has provoked sharp internal differences over policy toward the US. Already highly suspicious of the Reagan administration, the elite is united by a general conviction that SDI is an American gambit that may ultimately undercut past Soviet strategic gains and pose a grave new threat to Soviet security. 14 references.

  12. Systemic defense signaling in tomato

    Institute of Scientific and Technical Information of China (English)

    LI Changbao; SUN Jiaqiang; JIANG Hongling; WU Xiaoyan; LI Chuanyou

    2005-01-01

    The wound-inducible expression of proteinase inhibitors (PIs) genes in tomato provides a powerful model system to elucidate the signal transduction pathway of sys- temic defense response. An increasing body of evidence indi- cates that systemin and jasmonic acid (JA) work in the same signaling pathway to activate the expression of PIs and other defense-related genes. However, little is known about how systemin and JA interact to regulate cell to cell communica- tion over long distances. Genetic analysis of the systemin/JA signaling pathway in tomato plants provides a unique opportunity to dissect the mechanism by which peptide and oxylipin signals interact to coordinate systemic expression of defense-related genes. Previously, it has been proposed that systemin is the long-distance mobile signal for systemic expression of defense related genes. However, recent genetic approach provided new evidence that jasmonic acid, rather than systemin, functions as the systemic wound signal, and that the peptide systemin works to regulate the biosynthesis of JA.

  13. In Defense of Darwin's Theory.

    Science.gov (United States)

    Naylor, Bruce G.; Handford, Paul

    1985-01-01

    Examines issues regarding the defensibility and utility of natural selection as a scientific theory, focusing on the process of population change over time. Topics considered include criticisms of Darwinian theory, tautology and the meaning of fitness, the ability of theories to predict and explain, and the sufficiency of natural selection. (DH)

  14. [Search for new types of raw materials for antibacterial drugs].

    Science.gov (United States)

    Sidorenko, M L; Buzoleva, L S

    2012-01-01

    Antibacterial properties of the mycelium culture of Fomitopsis officinalis (Vill.: Fr.) Bondartsev et Singer were investigated. It was shown to be an additional source for production of antibacterial substances active against gramnegative bacteria. In the future, the use of Fomitopsis officinalis for production of antibacterial substances active against the pseudotuberculosis pathogen or pseudomonads is quite possible.

  15. Antibacterial Activity of Punica granatum Linn.

    Directory of Open Access Journals (Sweden)

    Kenan Tunç

    2013-08-01

    Full Text Available In this study, it was investigated that the extracts (ethanol, aceton, methanol, ethyl acetat obtained from fruit peels of the plant to whether has antibacterial effect against Streptococcus mitis CNCTC 4/77, Streptococcus salivarius CNCTC 64/59, Streptococcus mutans CNCTC 8/77, Staphylococcus epidermidis ATCC 12228, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Salmonella abony NCTC 6017, Salmonella typhimurium ATCC 14028, Enterococcus faecalis ATCC 29212, Bacillus subtilis ATCC 6633 bacteria strains in vitro. The antibacterial activity of extracts was evaluated according to disc diffusion method. It has been determined that pomegranate peel's extract had the highest inhibition zone diameters ( 18-30 mm against S. epidermidis and S. aureus bacteria strains. The antibacterial activity of plant against Streptococcus mitis is determined in this study for the first time.

  16. Antibacterial activity of eight Brazilian annonaceae plants.

    Science.gov (United States)

    Takahashi, Jacqueline A; Pereira, Cássia R; Pimenta, Lúcia P S; Boaventura, Maria Amélia D; Silva, Luiz G F E

    2006-01-01

    Sixteen extracts, obtained from eight Brazilian plants of Annonaceae family, were screened for their antibacterial activity: Xylopia frutescens, X. aromatica, X. amazonica, X. benthamii, Annona ambotay, A. crassiflora, A. muricata and A. cherimolia. Amongst the investigated extracts, six showed antibacterial activity against at least one of the tested organisms at the concentration of 100 microg/mL. The most active extracts were those prepared from X. frutescens, X. amazonica, and A. ambotay. A phytochemical screening showed the presence of anonaceus acetogenins in some active extracts. Eleven diterpenoids were also tested for comparison purposes. Six were natural products, previously isolated from Xylopia sp. (kaurenoic, frutoic, xylopic, 15beta-hydroxy-kaurenoic and trachylobanic acids plus kaurenol) and five were derivatives of such compounds, obtained by esterification or reduction reactions. Trachylobanic acid showed antibacterial activity against B. subtilis and S. aureus.

  17. Antibacterial resistance leadership group: open for business.

    Science.gov (United States)

    Chambers, Henry F; Bartlett, John G; Bonomo, Robert A; Chiou, Christine; Cosgrove, Sara E; Cross, Heather R; Daum, Robert S; Downing, Michele; Evans, Scott R; Knisely, Jane; Kreiswirth, Barry N; Lautenbach, Ebbing; Mickley, Brenda S; Patel, Robin; Pettigrew, Melinda M; Rodvold, Keith A; Spellberg, Brad; Fowler, Vance G

    2014-06-01

    Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.

  18. Actinopyga lecanora Hydrolysates as Natural Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Raheleh Ghanbari

    2012-12-01

    Full Text Available Actinopyga lecanora, a type of sea cucumber commonly known as stone fish with relatively high protein content, was explored as raw material for bioactive peptides production. Six proteolytic enzymes, namely alcalase, papain, pepsin, trypsin, bromelain and flavourzyme were used to hydrolyze A. lecanora at different times and their respective degrees of hydrolysis (DH were calculated. Subsequently, antibacterial activity of the A. lecanora hydrolysates, against some common pathogenic Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus and Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Pseudomonas sp. were evaluated. Papain hydrolysis showed the highest DH value (89.44%, followed by alcalase hydrolysis (83.35%. Bromelain hydrolysate after one and seven hours of hydrolysis exhibited the highest antibacterial activities against Pseudomonas sp., P. aeruginosa and E. coli at 51.85%, 30.07% and 30.45%, respectively compared to the other hydrolysates. Protein hydrolysate generated by papain after 8 h hydrolysis showed maximum antibacterial activity against S. aureus at 20.19%. The potent hydrolysates were further fractionated using RP-HPLC and antibacterial activity of the collected fractions from each hydrolysate were evaluated, wherein among them only three fractions from the bromelain hydrolysates exhibited inhibitory activities against Pseudomonas sp., P. aeruginosa and E. coli at 24%, 25.5% and 27.1%, respectively and one fraction of papain hydrolysate showed antibacterial activity of 33.1% against S. aureus. The evaluation of the relationship between DH and antibacterial activities of papain and bromelain hydrolysates revealed a meaningful correlation of four and six order functions.

  19. Evaluation of Antibacterial Potentiality of a Cyclopenta Naphthalene Tetraol Terpenoid Isolated from Curcuma caesia Roxb.

    Directory of Open Access Journals (Sweden)

    Padma Chatterjee

    2014-03-01

    Full Text Available The assessment of antibacterial potentiality of 2,3,4,8a,9,9a-hexamethyl-2,3,3a,4,4a,5,8,8a,9,9a – decahydro - 1H – cyclopenta [b] naphthalene -1,2,3a,4a-tetraol was the primary objective of this paper followed by its physicochemical characterization. Chemical characterisation of 2, 3, 4, 8a, 9, 9a-hexamethyl-2,3,3a,4,4a,5,8,8a,9,9a-decahydro-1H-cyclopenta [b] naphthalene-1,2,3a,4a-tetraol was done through UV, IR (FT-IR, HRMS and NMR spectroscopic techniques. Assessment of its antibacterial activity was performed using agar cup method and disc diffusion assay respectively. The antibacterial compound was terpenoid in nature and identified as 2, 3, 4, 8a, 9, 9a-hexamethyl-2,3,3a,4,4a,5,8,8a,9,9a-decahydro-1H-cyclopenta [b] naphthalene-1,2,3a,4a-tetraol. The MIC values tested against different plant pathogenic fungi and bacteria are different. The MIC values of this compound was 365 μg/ml, 274 μg/ml, 389 μg/ml, 443 μg/ml tested against the bacterium Serratia marcescens, Erwinia herbicola, Xanthomonas sp. and Arthrobacter chlorophenolicus respectively. Best of our knowledge this was the first report of presence of 2, 3, 4, 8a, 9, 9a-hexamethyl-2, 3, 3a, 4, 4a, 5, 8, 8a, 9, 9a-decahydro-1H-cyclopenta [b] naphthalene-1,2,3a,4a-tetraol in plants. Due to its antibacterial property it may function in plant defense or commercialize as an ecofriendly crop protectant.

  20. Performance of secondary parasitoids on chemically defended and undefended hosts

    NARCIS (Netherlands)

    van Nouhuys, S.; Reudler, J.H.; Biere, A.; Harvey, J.A.

    2012-01-01

    Defensive chemicals produced by plants can travel up the food chain by being sequestered by herbivores, and then in turn being sequestered by their parasitoids. Insect species with wide host ranges are predicted to perform poorly in the face of specific chemical defence. However, a species at a high

  1. A tritrophic signal that attracts parasitoids to host-damaged plants withstands disruption by non-host herbivores

    Directory of Open Access Journals (Sweden)

    Turlings Ted CJ

    2010-11-01

    Full Text Available Abstract Background Volatiles emitted by herbivore-infested plants are highly attractive to parasitoids and therefore have been proposed to be part of an indirect plant defense strategy. However, this proposed function of the plant-provided signals remains controversial, and it is unclear how specific and reliable the signals are under natural conditions with simultaneous feeding by multiple herbivores. Phloem feeders in particular are assumed to interfere with plant defense responses. Therefore, we investigated how attack by the piercing-sucking cicadellid Euscelidius variegatus influences signaling by maize plants in response to the chewing herbivore Spodoptera littoralis. Results The parasitoid Cotesia marginiventris strongly preferred volatiles of plants infested with its host S. littoralis. Overall, the volatile emissions induced by S. littoralis and E. variegatus were similar, but higher levels of certain wound-released compounds may have allowed the wasps to specifically recognize plants infested by hosts. Expression levels of defense marker genes and further behavioral bioassays with the parasitoid showed that neither the physiological defense responses nor the attractiveness of S. littoralis infested plants were altered by simultaneous E. variegatus attack. Conclusions Our findings imply that plant defense responses to herbivory can be more robust than generally assumed and that ensuing volatiles convey specific information about the type of herbivore that is attacking a plant, even in complex situations with multiple herbivores. Hence, the results of this study support the notion that herbivore-induced plant volatiles may be part of a plant's indirect defense stratagem.

  2. Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia.

    Science.gov (United States)

    Hilliard, Kristie L; Allen, Eri; Traber, Katrina E; Kim, Yuri; Wasserman, Gregory A; Jones, Matthew R; Mizgerd, Joseph P; Quinton, Lee J

    2015-10-01

    Pneumonia and infection-induced sepsis are worldwide public health concerns. Both pathologies elicit systemic inflammation and induce a robust acute-phase response (APR). Although APR activation is well regarded as a hallmark of infection, the direct contributions of liver activation to pulmonary defense during sepsis remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we evaluated the role of liver STAT3 activity in promoting host defense in the context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS; 5 mg/kg of body weight) was followed by intratracheal Escherichia coli (10(6) CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3(-/-)). Pneumonia alone (without endotoxemia) was effectively controlled in the absence of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3(-/-) mice, with significantly reduced levels of circulating and airspace acute-phase proteins, exhibited significantly elevated lung and blood bacterial burdens and mortality. These data suggested that STAT3-dependent liver responses are necessary to promote host defense. While neither recruited airspace neutrophils nor lung injury was altered in endotoxemic hepSTAT3(-/-) mice, alveolar macrophage reactive oxygen species generation was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3(-/-) mice allowed greater bacterial growth ex vivo. These results suggest that hepatic STAT3 activation promotes both cellular and humoral lung defenses. Taken together, induction of liver STAT3-dependent gene expression programs is essential to countering the deleterious consequences of sepsis on pneumonia susceptibility. PMID:26216424

  3. Tick-Host Specificity

    OpenAIRE

    Hoogstraal, H.; Aeschlimann, André

    2010-01-01

    A review the various patterns of tick-host relationships are discussed in detail in order to answer the following questions : 1. How, when and where did host specificity of each parasite group evolve ? 2. How strict is specificity in each case ? 3. Why and under what circumstances does specificity break down ? The authors present several definitions which characterize the various degrees of parasitic specificity existing today between ticks and their hosts. Tick-host relationships are ...

  4. Civil Defense, U. S. A.: A Programmed Orientation to Civil Defense. Unit 1. Civil Defense - Protection Against What?

    Science.gov (United States)

    Defense Civil Preparedness Agency (DOD), Battle Creek, MI.

    An explanation of the need for civil defense in nuclear and natural disasters is presented. A brief historical background of civil defense is given. Major topics include: (1) Types of disasters, (2) Probable objectives of a nuclear attack on the United States, (3) The major defensive measures against a nuclear attack, (4) Some reasons for low…

  5. Incompatibility between plant-derived defensive chemistry and immune response of two sphingid herbivores.

    Science.gov (United States)

    Lampert, Evan C; Bowers, M Deane

    2015-01-01

    Herbivorous insects use several different defenses against predators and parasites, and tradeoffs among defensive traits may occur if these traits are energetically demanding. Chemical defense and immune response potentially can interact, and both can be influenced by host plant chemistry. Two closely related caterpillars in the lepidopteran family Sphingidae are both attacked by the same specialist endoparasitoid species but have mostly non-overlapping host plant ranges that differ in secondary chemistry. Ceratomia catalpae is a specialist on Catalpa and also will feed on Chilopsis, which both produce iridoid glycosides. Ceratomia undulosa consumes members of the Oleaceae, which produce seco-iridoid glycosides. Immune response of the two species on a typical host plant species (Catalpa bignonioides for C. catalpa; Fraxinus americana for C. undulosa) was compared using a melanization assay, and did not differ. In a second experiment, the iridoid glycoside catalpol was added to the diets of both insects, and growth rate, mass, chemical defense, and immune response were evaluated. Increased dietary catalpol weakened the immune response of C. undulosa and altered the development rate of C. catalpae by prolonging the third instar and accelerating the fourth instar. Catalpol sequestration was negatively correlated with immune response of C. catalpae, while C. undulosa was unable to sequester catalpol. These results show that immune response can be negatively influenced by increasing concentrations of sequestered defensive compounds. PMID:25516226

  6. Department of Defense PERSEREC (DOD PERSEREC)

    Data.gov (United States)

    Social Security Administration — The purpose of this agreement is for SSA to verify SSN information for Defense Manpower Data Center (DMDC) of the Department of Defense. DMDC will use the SSA data...

  7. Territorial Defense, Education, and Interculturalism

    OpenAIRE

    Claudia Patricia Sierra Pardo

    2011-01-01

    The article carries out a series of reflections regarding the social and economic conditions in which the cultivation of oil palm affected the Bajo Atrato region of the Department of Chocó at the end of the nineteen nineties. It also discusses the actions carried out by communities, companies, and organizations in solidarity with the region’s cause, since these expressions make it possible to understand the role of organization and education in territorial defense processes. Finally, the arti...

  8. Antibacterial paperboard packaging using microfibrillated cellulose.

    Science.gov (United States)

    Lavoine, Nathalie; Desloges, Isabelle; Manship, Brigitte; Bras, Julien

    2015-09-01

    The industry and consumers are focusing more and more on the development of biodegradable and lightweight food-packaging materials, which could better preserve the quality of the food and improve its shelf-life. In an attempt to meet these requirements, this study presents a novel bio-substrate able to contain active bio-molecules for future food-packaging applications. Based on a paperboard substrate, the development of an antibacterial bio-packaging material is, therein, achieved using a chlorhexidine digluconate (CHX) solution as a model of an antibacterial molecule, mixed with microfibrillated cellulose (MFC) and used as coating onto paperboard samples. AFM and FE-SEM analyses were performed to underline the nanoporous MFC network able to trap and to progressively release the CHX molecules. The release study of CHX was conducted in an aqueous medium and showed a lower proportion (20 %) of CHX released when using MFC. This led to the constant release of low amounts of CHX over 40 h. Antibacterial tests were carried out to assess the preservation of the antibacterial activity of the samples after the release studies. Samples remained active against Bacillus subtilis, with better results being obtained when MFC was used. The preservation of the quality of a model food was finally evaluated paving the way for future promising applications in the food packaging industry.

  9. Characterization of antibacterial silver coated yarns.

    Science.gov (United States)

    Pollini, M; Russo, M; Licciulli, A; Sannino, A; Maffezzoli, A

    2009-11-01

    Surface treatments of textile fibers and fabrics significantly increase their performances for specific biomedical applications. Nowadays, silver is the most used antibacterial agent with a number of advantages. Among them, it is worth to note the high degree of biocompatibility, an excellent resistance to sterilization conditions, antibacterial properties with respect to different bacteria associated with a long-term of antibacterial efficiency. However, there are only a few antibacterial fibres available, mainly synthetic with high production cost and limited effectiveness. Cotton yarns with antimicrobial properties are most suitable for wound healing applications and other medical treatments thanks to their excellent moisture absorbance while synthetic based fibres are most suitable for industrial applications such as automotive tapestry and air filters. The silver-coated fibers were developed applying an innovative and low cost silver deposition technique for natural and synthetic fibers or yarns. The structure and morphology of the silver nanoclusters on the fibers was observed by scanning electron microscopy (SEM), atomic force microscopy analysis (AFM) and XRD analysis, and quantitatively confirmed by thermogravimetric analysis (TGA) measurements. Good silver coating stability has been confirmed performing several industrial washing. Antimicrobial tests with Escherichia coli were performed. PMID:19526328

  10. Antibacterial activity of Pulicaria dysenterica extracts.

    Science.gov (United States)

    Nickavar, Bahman; Mojab, Faraz

    2003-06-01

    Aqueous, methanolic and chloroformic extracts of Pulicaria dysenterica aerial parts were tested for their antibacterial activity using the disc-diffusion assay technique. The methanolic extract was found to be the most effective extract against three out of six tested bacteria. All of the extracts were active against Vibrio cholera.

  11. Two New Antibacterial Flavanones from Sophora flavescens

    Institute of Scientific and Technical Information of China (English)

    Mei Ai CAO; Xiao Bai SUN; Pei Hua ZHAO; Cheng Shan YUAN

    2006-01-01

    Two new lavandulylated flavanones, (2R, 3R)-8-1avandulyl-2'-methoxy-5, 7, 4'-trihydroxyflavanonol (1) and 8-1avandulyl-5, 7, 4'-trihydroxyflavonol (2), were isolated from the dry roots of Sophara flavescens. Their structures were elucidated on the basis of spectroscopic data. Compounds 1 and 2 exhibited significant antibacterial activities.

  12. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  13. Antibacterial Activity of Honey on Cariogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Zahra Khamverdi

    2013-01-01

    Full Text Available Objective: Honey has antibacterial activity. The aim of this study was to evaluate the antibacterial activity of honey on Streptococcus mutans and Lactobacillus.Materials and Methods: In this in vitro study, solutions containing 0%, 5%, 10%, 20%, 50% and100%(w/v of natural Hamadan honey were prepared. Each blood (nutrient agar plate was then filled with dilutions of the honey. The strains of bacteria were inoculated in blood agar for 24 hours at 37oC and were adjusted according to the McFarland scale (10×10 cfumcl -1. All assays were repeated 10 times for each of the honey concentrations. Data were analyzed by non parametric Chi-Square test. Statistical significance was set at α=0.05.Results: Significant antibacterial activity was detected for honey on Streptococcus mutans in concentrations more than 20% and on Lactobacillus in 100% concentration (P<0.05.Conclusion: It seems that antibacterial activity of honey could be used for prevention and reduction of dental caries.

  14. Antibacterial activity of selected Egyptian ethnomedicinal plants

    Directory of Open Access Journals (Sweden)

    Mashait, M.

    2013-01-01

    Full Text Available Aims: Medicinal plants have recently received the attention of the antimicrobial activity of plants and their metabolites due to the challenge of growing incidences of drug-resistant pathogens. The aims of this study were to determine the antibacterial activities of plant extracts used as ethnomedicinal in Egypt. Methodology and Results: Investigations were carried out to assess the antibacterial efficiency of 11 plant extracts used as ethnopharmacological among Egyptian native people against infectious diseases. Crude methanol, ethanol,chloroform, hexane, acetone and aqueous extract of plants were tested for antibacterial activity in vitro against ten bacterial isolates using the disc diffusion method test. Discs were impregnated with 2 mg/mL of different solvent extracts. Among all the crude extracts, the methanol extract showed the highest activity than other extracts. P. harmala and S. officinalis exhibited highest antibacterial activity against gram positive and negative bacteria while the remainingplants extracts showed less activity. All the plant extracts showed no significant effect against the Bordetella bronchisepta ATCC 4617 except the extracts of M. fragrans and L. sativum. E. coli is the most sensitive microorganism tested, with the lowest MIC value (0.5 mg/mL in the presence of the plant extract of P. harmala and S. officinalis.Conclusion, significance and impact of study: Results obtained herein, may suggest that the ethnomedicinal Egyptian plants possess antimicrobial activity and therefore, they can be used in biotechnological fields as natural preservative ingredients in food and/or pharmaceutical industry.

  15. CSRF Vulnerabilities and Defensive Techniques

    Directory of Open Access Journals (Sweden)

    Rupali D. Kombade

    2012-02-01

    Full Text Available Web applications are now part of day to day life due to their user friendly environment as well as advancement of technology to provide internet facilities, but these web applications brought lot of threats with them and these threats are continuously growing, one of the these threat is Cross Site Request Forgery(CSRF. CSRF attack is immerged as serious threat to web applications which based on the vulnerabilities present in the normal request response pattern of HTTP protocol. It is difficult to detect and hence it is present in most of the existing web applications. CSRF attack occurs when a malicious web site causes a user’s web browser to perform an unwanted action on a trusted site. It is listed in OWASP’s top ten Web Application attacks list. In this survey paper we will study CSRF attack, CSRF vulnerabilities and its defensive measures. We have compared various defense mechanisms to analyse the best defense mechanism. This study will help us to build strong and robust CSRF protection mechanism.

  16. Nicotine's defensive function in nature.

    Directory of Open Access Journals (Sweden)

    Anke Steppuhn

    2004-08-01

    Full Text Available Plants produce metabolites that directly decrease herbivore performance, and as a consequence, herbivores are selected for resistance to these metabolites. To determine whether these metabolites actually function as defenses requires measuring the performance of plants that are altered only in the production of a certain metabolite. To date, the defensive value of most plant resistance traits has not been demonstrated in nature. We transformed native tobacco(Nicotiana attenuata with a consensus fragment of its two putrescine N-methyl transferase (pmt genes in either antisense or inverted-repeat (IRpmt orientations. Only the latter reduced (by greater than 95% constitutive and inducible nicotine. With D(4-nicotinic acid (NA, we demonstrate that silencing pmt inhibits nicotine production, while the excess NA dimerizes to form anatabine. Larvae of the nicotine-adapted herbivore Manduca sexta (tobacco hornworm grew faster and, like the beetle Diabrotica undecimpunctata, preferred IRpmt plants in choice tests. When planted in their native habitat, IRpmt plants were attacked more frequently and, compared to wild-type plants, lost 3-fold more leaf area from a variety of native herbivores, of which the beet armyworm, Spodoptera exigua, and Trimerotropis spp. grasshoppers caused the most damage. These results provide strong evidence that nicotine functions as an efficient defense in nature and highlights the value of transgenic techniques for ecological research.

  17. Second Line of Defense Spares Program

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

    2012-11-20

    During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

  18. Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks.

    Science.gov (United States)

    Flentie, Kelly; Garner, Ashley L; Stallings, Christina L

    2016-05-01

    Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress,M. tuberculosis is prepared for battle against the host defense and able to persist within the human population.

  19. 22 CFR 120.9 - Defense service.

    Science.gov (United States)

    2010-04-01

    ... Defense service. (a) Defense service means: (1) The furnishing of assistance (including training) to foreign persons, whether in the United States or abroad in the design, development, engineering... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense service. 120.9 Section 120.9...

  20. 75 FR 32416 - Defense Science Board

    Science.gov (United States)

    2010-06-08

    ... of the Secretary Defense Science Board AGENCY: Department of Defense (DoD). ACTION: Notice of advisory committee meeting. SUMMARY: The Defense Science Board Task Force on the Survivability of DoD... Science Board Threat Reduction Advisory Committee (TRAC) Task Force findings, recommendations and...

  1. A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa

    DEFF Research Database (Denmark)

    Mohanty, Tirthankar; Sjögren, Jonathan; Kahn, Fredrik;

    2015-01-01

    Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo...

  2. Genome adaptations of a tripartite motif protein for retroviral defense in cattle and sheep

    Science.gov (United States)

    Tripartite motif (TRIM) genes encode proteins composed of RING, B-box, and coiled coil motif domains. Primate TRIM5' has been shown to be a primary determinant of retroviral host cell range restriction in primates. TRIM5 restriction was originally thought to be a primate-specific defense mechanism...

  3. Platelet microbicidal activity is an important defense factor against viridans streptococcal endocarditis

    NARCIS (Netherlands)

    Krijgsveld, J; Joldersma, W; Zaat, SAJ; van der Werff, J.

    2001-01-01

    To study the role of platelet microbicidal activity in host defense against infective endocarditis (IE) due to viridans streptococci (VS), the susceptibility to platelet releasate of blood and oral VS isolates from patients with and without IE was compared. The influence of neutralization of platele

  4. Phytophthora infestans RXLR effector AVR1 and its host target Sec5

    NARCIS (Netherlands)

    Du, Y.

    2014-01-01

    Summary Late blight, caused by the oomycete Phytophthora infestans, is one of the most devastating potato diseases worldwide. To successfully colonize its host, P. infestans secretes a plethora of RXLR effectors that translocate into host cells to modulate plant defense. The RXLR ef

  5. Quantifying the dynamics of viruses and the cellular immune response of the host

    NARCIS (Netherlands)

    Althaus, C.L.

    2009-01-01

    Infections can be caused by viruses, which attack certain cells within an infected host. However, the immune system of the host has evolved remarkable defense mechanisms that counter against an infection. In particular, so-called cytotoxic T lymphocytes can recognize and eliminate infected cells. Th

  6. 76 FR 72391 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-11-23

    ... (DLA) published a Notice of Availability (NOA) in the Federal Register (76 FR 28757) announcing the... of the Secretary Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION:...

  7. Pathogen mimicry of host protein-protein interfaces modulates immunity.

    Science.gov (United States)

    Guven-Maiorov, Emine; Tsai, Chung-Jung; Nussinov, Ruth

    2016-10-01

    Signaling pathways shape and transmit the cell's reaction to its changing environment; however, pathogens can circumvent this response by manipulating host signaling. To subvert host defense, they beat it at its own game: they hijack host pathways by mimicking the binding surfaces of host-encoded proteins. For this, it is not necessary to achieve global protein homology; imitating merely the interaction surface is sufficient. Different protein folds often interact via similar protein-protein interface architectures. This similarity in binding surfaces permits the pathogenic protein to compete with a host target protein. Thus, rather than binding a host-encoded partner, the host protein hub binds the pathogenic surrogate. The outcome can be dire: rewiring or repurposing the host pathways, shifting the cell signaling landscape and consequently the immune response. They can also cause persistent infections as well as cancer by modulating key signaling pathways, such as those involving Ras. Mapping the rewired host-pathogen 'superorganism' interaction network - along with its structural details - is critical for in-depth understanding of pathogenic mechanisms and developing efficient therapeutics. Here, we overview the role of molecular mimicry in pathogen host evasion as well as types of molecular mimicry mechanisms that emerged during evolution.

  8. Susceptibility of Porphyromonas gingivalis and Streptococcus mutans to Antibacterial Effect from Mammea americana

    Directory of Open Access Journals (Sweden)

    Alejandra Herrera Herrera

    2014-01-01

    Full Text Available The development of periodontal disease and dental caries is influenced by several factors, such as microorganisms of bacterial biofilm or commensal bacteria in the mouth. These microorganisms trigger inflammatory and immune responses in the host. Currently, medicinal plants are treatment options for these oral diseases. Mammea americana extracts have reported antimicrobial effects against several microorganisms. Nevertheless, this effect is unknown against oral bacteria. Therefore, the aim of this study was to evaluate the antibacterial effect of M. americana extract against Porphyromonas gingivalis and Streptococcus mutans. For this, an experimental study was conducted. Ethanolic extract was obtained from seeds of M. americana (one oil phase and one ethanolic phase. The strains of Porphyromonas gingivalis ATCC 33277 and Streptococcus mutans ATCC 25175 were exposed to this extract to evaluate its antibacterial effect. Antibacterial activity was observed with the two phases of M. americana extract on P. gingivalis and S. mutans with lower MICs (minimum inhibitory concentration. Also, bactericidal and bacteriostatic activity was detected against S. mutans, depending on the concentration of the extract, while on M. americana extract presented only bacteriostatic activity against P. gingivalis. These findings provide important and promising information allowing for further exploration in the future.

  9. Priming of antiherbivore defensive responses in plants

    Institute of Scientific and Technical Information of China (English)

    Jinwon Kim; Gary W.Felton

    2013-01-01

    Defense priming is defined as increased readiness of defense induction.A growing body of literature indicates that plants (or intact parts of a plant) are primed in anticipation of impending environmental stresses,both biotic and abiotic,and upon the following stimulus,induce defenses more quickly and strongly.For instance,some plants previously exposed to herbivore-inducible plant volatiles (HIPVs) from neighboring plants under herbivore attack show faster or stronger defense activation and enhanced insect resistance when challenged with secondary insect feeding.Research on priming of antiherbivore defense has been limited to the HIPV-mediated mechanism until recently,but significant advances were made in the past three years,including non-HIPV-mediated defense priming,epigenetic modifications as the molecular mechanism of priming,and others.It is timely to consider the advances in research on defense priming in the plantinsect interactions.

  10. Web hosting for dummies

    CERN Document Server

    Pollock, Peter

    2013-01-01

    Host your own website or blog with this unique guide If you'd like to make the leap from a hosted environment to a self-hosted service, this book is for you. You may be making the move from casual blogging to professional blogging. Or, you might already be self-hosting, but want a good guide to show you how to get more out of your plan. In simple, easy-to-understand language, this helpful book breaks down all the functions of web hosting for self-hosted users, from setting up new e-mail accounts to backing up and securing your site, analyzing server logs, choosing a platform to ins

  11. FUETAP concrete - an alternative radioactive waste host

    International Nuclear Information System (INIS)

    These tailored autoclaved concretes (FUETAP concentrates) offer a number of advantages as hosts for a wide variety of radioactive wastes. They are formed at low temperatures and pressures (1000C and 0.1 MPa) from readily available raw materials and require no new processing technology. The extreme latitude in concrete formulations ensures the acceptance of the gamut of waste materials. The leachability of nuclides from the resulting ceramic-like concretes is quite low with essentially no prospect of pressure build-up from long-term self-irradiation in the final storage containers. The solids are thermally stable up to at least 9000C. Additional studies are in progress to verify that FUETAP concretes are acceptable alternative waste hosts for defense, TRU, and commercial high-level radioactive waste. (orig.)

  12. Digenean larvae—the cause and beneficiaries of the changes in host snails’ thermal behavior

    OpenAIRE

    Żbikowska, Elżbieta; Żbikowski, Janusz

    2015-01-01

    Parasite-induced changes in host’s thermal preferences not only can be interpreted as a physiological defense response of the host but also can represent a pathological manifestation of the parasite. Both may become established in host-parasite relationships if they are beneficial for at least one of the counterparts. This study investigates parasite-induced changes in the thermoregulatory behavior of first intermediate hosts of Digenea (i.e. Lymnaea stagnalis and Planorbarius corneus), infec...

  13. Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria.

    Science.gov (United States)

    Achtman, Ariel H; Pilat, Sandra; Law, Charity W; Lynn, David J; Janot, Laure; Mayer, Matt L; Ma, Shuhua; Kindrachuk, Jason; Finlay, B Brett; Brinkman, Fiona S L; Smyth, Gordon K; Hancock, Robert E W; Schofield, Louis

    2012-05-23

    Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defense regulator (IDR) peptides, based on host defense peptides. The Plasmodium berghei ANKA model of experimental cerebral malaria was adapted to use as a preclinical screen by combining late-stage intervention in established infections with advanced bioinformatic analysis of early transcriptional changes in co-regulated gene sets. Coadministration of IDR-1018 with standard first-line antimalarials increased survival of infected mice while down-regulating key inflammatory networks associated with fatality. Thus, IDR peptides provided host-directed adjunctive therapy for severe disease in combination with antimalarial treatment.

  14. SQL Injection Attacks and Defense

    CERN Document Server

    Clarke, Justin

    2012-01-01

    SQL Injection Attacks and Defense, First Edition: Winner of the Best Book Bejtlich Read Award "SQL injection is probably the number one problem for any server-side application, and this book unequaled in its coverage." -Richard Bejtlich, Tao Security blog SQL injection represents one of the most dangerous and well-known, yet misunderstood, security vulnerabilities on the Internet, largely because there is no central repository of information available for penetration testers, IT security consultants and practitioners, and web/software developers to turn to for help. SQL Injection Att

  15. Cyber defense and situational awareness

    CERN Document Server

    Kott, Alexander; Erbacher, Robert F

    2015-01-01

    This book is the first publication to give a comprehensive, structured treatment to the important topic of situational awareness in cyber defense. It presents the subject in a logical, consistent, continuous discourse, covering key topics such as formation of cyber situational awareness, visualization and human factors, automated learning and inference, use of ontologies and metrics, predicting and assessing impact of cyber attacks, and achieving resilience of cyber and physical mission. Chapters include case studies, recent research results and practical insights described specifically for th

  16. Territorial Defense, Education, and Interculturalism

    Directory of Open Access Journals (Sweden)

    Claudia Patricia Sierra Pardo

    2011-10-01

    Full Text Available The article carries out a series of reflections regarding the social and economic conditions in which the cultivation of oil palm affected the Bajo Atrato region of the Department of Chocó at the end of the nineteen nineties. It also discusses the actions carried out by communities, companies, and organizations in solidarity with the region’s cause, since these expressions make it possible to understand the role of organization and education in territorial defense processes. Finally, the article examines the different tensions, struggles, challenges, and contradictions inherent to these types of processes.

  17. Bordetella pertussis modulates human macrophage defense gene expression.

    Science.gov (United States)

    Valdez, Hugo Alberto; Oviedo, Juan Marcos; Gorgojo, Juan Pablo; Lamberti, Yanina; Rodriguez, Maria Eugenia

    2016-08-01

    Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages.

  18. Defensive bacteriome symbiont with a drastically reduced genome.

    Science.gov (United States)

    Nakabachi, Atsushi; Ueoka, Reiko; Oshima, Kenshiro; Teta, Roberta; Mangoni, Alfonso; Gurgui, Mihaela; Oldham, Neil J; van Echten-Deckert, Gerhild; Okamura, Keiko; Yamamoto, Kohei; Inoue, Hiromitsu; Ohkuma, Moriya; Hongoh, Yuichi; Miyagishima, Shin-ya; Hattori, Masahira; Piel, Jörn; Fukatsu, Takema

    2013-08-01

    Diverse insect species harbor symbiotic bacteria, which play important roles such as provisioning nutrients and providing defense against natural enemies [1-6]. Whereas nutritional symbioses are often indispensable for both partners, defensive symbioses tend to be of a facultative nature [1-12]. The Asian citrus psyllid Diaphorina citri is a notorious agricultural pest that transmits Liberibacter spp. (Alphaproteobacteria), causing the devastating citrus greening disease or Huanglongbing [13, 14]. In a symbiotic organ called the bacteriome, D. citri harbors two distinct intracellular symbionts: a putative nutrition provider, Carsonella_DC (Gammaproteobacteria), and an unnamed betaproteobacterium with unknown function [15], for which we propose the name "Candidatus Profftella armatura." Here we report that Profftella is a defensive symbiont presumably of an obligate nature with an extremely streamlined genome. The genomes of Profftella and Carsonella_DC were drastically reduced to 464,857 bp and 174,014 bp, respectively, suggesting their ancient and mutually indispensible association with the host. Strikingly, 15% of the small Profftella genome encoded horizontally acquired genes for synthesizing a novel polyketide toxin. The toxin was extracted, pharmacologically and structurally characterized, and designated diaphorin. The presence of Profftella and its diaphorin-biosynthetic genes was perfectly conserved in the world's D. citri populations. PMID:23850282

  19. Evaluation of in vitro antibacterial effect of room curing polymethylmethacrylate material adding nano-silver base inorganic antibacterial agents

    International Nuclear Information System (INIS)

    Objective: To investigate the antibacterial effect of room curing polymethylmethacrylate (PMMA) material adding nano-silver base inorganic antibacterial agent and to detect the changes of its mechanical property. Methods: Nano-silver base inorganic antibacterial agent was added to the room curing PMMA material in the range of 0.5% -3.0% at an interval of 0.5% by ball milling specimen. Antibacterial rates of the specimens were detected by film method. Bending strength, impact strength, and wear resistance of the specimens were respectively detected on electronic universal testing machine, impact test machine and friction and wear test machine. Results: The antibacterial rates of Streptococcus mutans and Candida albicans were more than 50% when antibiotics content was 1.0% . The antibacterial rates of Streptococcus mutans and Candida albicans were more than 90% when the antibiotics content was 2.5% . The three mechanical properties were increased compared with control group when the antibacterial agents were in the range of 1.0% -1.5% . Then the three mechanical properties were decreased with the increasing of antimicrobial concentration. When the antibiotics content was 2.0% , the wear resistance had significant difference compared with control group (P<0.05); when the antibiotics content was 2.5% , the bending strength and impact strength had significant difference compared with control group (P<0.05). Conclusion: The antibacterial effect of room curing PMMA adding nano-silver base inorganic antibacterial agent is ideal. The antibacterial rate is increased gradually with the increasing content of antibacterial agents. There is no significant effect on the mechanical properties of room curing PMMA material, but the antibacterial effects are satisfied when the content of antibacterial agents is 2.0% . (authors)

  20. Synthesis of highly efficient antibacterial agent Ag doped ZnO nanorods: Structural, Raman and optical properties

    Energy Technology Data Exchange (ETDEWEB)

    Jan, Tariq; Iqbal, Javed, E-mail: javed.saggu@iiu.edu.pk [Laboratory of Nanoscience and Technology, Department of Physics, International Islamic University Islamabad (Pakistan); Ismail, Muhammad [Institute of Biomedical and Genetic Engineering (IBGE), Islamabad (Pakistan); Mahmood, Arshad [Nano Devices Labs, National Institute of Lasers and Optronics, Islamabad (Pakistan)

    2014-04-21

    Here, synthesis, structural, morphological, Raman, optical properties and antibacterial activity of undoped and Ag doped ZnO nanorods by chemical co-precipitation technique have been reported. Structural analysis has revealed that Ag doping cannot deteriorate the structure of ZnO and wurtzite phase is maintained. Lattice constants are found to be decreased with the Ag doping. Fourier transform infrared and Raman spectroscopy also confirm the X-ray diffraction results. Scanning electron microscopy results have demonstrated the formation of ZnO nanorods with average diameter and length of 96 nm and 700 nm, respectively. Raman spectroscopy results suggest that the Ag doping enhances the number of defects in ZnO crystal. It has been found from optical study that Ag doping results in positional shift of band edge absorption peak. This is attributed to the successful incorporation of Ag dopant into ZnO host matrix. The antibacterial activity of prepared nanorods has been determined by two different methods and compared to that of undoped ZnO nanorods. Ag doped ZnO nanorods exhibit excellent antibacterial activity as compared to that of undoped ZnO nanorods. This excellent antibacterial activity may be attributed to the presence of oxygen vacancies and Zn{sup 2+} interstitial defects. Our preliminary findings suggest that Ag doped ZnO nanorods can be used externally to control the spreading of infections related with tested bacterial strains.

  1. ANTIBACTERIAL PROPERTIES AND DRYING EFFECTS OF FLAX DENIM AND ANTIBACTERIAL PROPERTIES OF NONWOVEN FLAX FABRIC

    Directory of Open Access Journals (Sweden)

    David T.W. Chun

    2010-02-01

    Full Text Available A modification of “AATCC Test Method 100-1999” was used for assaying for bacteriostatic/antibacterial properties of denim containing various flax concentrations. Since no direct evidence that increasing the flax content of fabric imparted the fabric with increased bacteriostatic properties was found against the control bacteria, Staphylococcus aureus and Klebsiella pneumoniae, other possible explanations for the long held presumption that flax fabric exhibited antibacterial properties was sought. Because the appearance of having antibacterial or bacteriostatic properties might be imitated if the flax content would decrease the time fabric would be moist enough for bacterial growth, the effect of drying was evaluated. When flax fabric was saturated and the moisture lost during incubation was measured, there was no improved drying associated with increased flax content. When untreated nonwoven flax was evaluated as possibly containing more ‘antibacterial’ or bacteriostatic components than scoured nonwoven flax material, the population densities increased. This increase suggests that the unscoured nonwoven flax contain compo-nents that support bacterial growth to the extent that bacteriostatic or antibacterial components, if any, are overwhelmed by the components that support bacterial growth. In tests involving the control bacteria, Staphylococcus aureus and Klebsiella pneumoniae, increasing the flax content of flax fabric did not demonstrate increased antibacterial properties.

  2. Analysis and design of a cooperative weapon assignment module for advanced battle manager of a ballistic missile defense system

    OpenAIRE

    Brown, Willie D.

    2006-01-01

    The United States is in the midst of an ambitious effort to build and deploy a wide range of ballistic missile defense systems. These ballistic missile defense systems will be effective against a host of current and postulated threats from ballistic missiles. In this thesis study, we explore the process of enhancing the effectiveness of weapon assignment for a system of systems. First, analysis of information is drawn from current proposed system of the ABM and its construction from the ...

  3. Application of SYNROC to high-level defense wastes

    International Nuclear Information System (INIS)

    The SYNROC method for immobilization of high-level nuclear reactor wastes is currently being applied to US defense wastes in tank storage at Savannah River, South Carolina. The minerals zirconolite, perovskite, and hollandite are used in SYNROC D formulations to immobilize fission products and actinides that comprise up to 10% of defense waste sludges and coexisting solutions. Additional phases in SYNROC D are nepheline, the host phase for sodium; and spinel, the host for excess aluminum and iron. Up to 70 wt % of calcined sludge can be incorporated with 30 wt % of SYNROC additives to produce a waste form consisting of 10% nepheline, 30% spinel, and approximately 20% each of the radioactive waste-bearing phases. Urea coprecipitation and spray drying/calcining methods have been used in the laboratory to produce homogeneous, reactive ceramic powders. Hot pressing and sintering at temperatures from 1000 to 11000C result in waste form products with greater than 97% of theoretical density. Hot isostatic pressing has recently been implemented as a processing alternative. Characterization of waste-form mineralogy has been done by means of XRD, SEM, and electron microprobe. Leaching of SYNROC D samples is currently being carried out. Assessment of radiation damage effects and physical properties of SYNROC D will commence in FY 81

  4. Application of SYNROC to high-level defense wastes

    International Nuclear Information System (INIS)

    The SYNROC method for immobilization of high-level nuclear reactor wastes is currently being applied to US defense wastes in tank storage at Savannah River, South Carolina. The minerals zirconolite, perovskite, and hollandite are used in SYNROC D formulations to immobilize fission products and actinides that comprise up to 10% of defense waste sludges and coexisting solutions. Additional phase in SYNROC D are nepheline, the host phase for sodium; and spinel, the host for excess aluminum and iron. Up to 70 wt % of calcined sludge can be incorporated with 30 wt % of SYNROC additives to produce a waste form consisting of 10% nepheline, 30% spinel, and approximately 20% each of the radioactive waste-bearing phases. Urea coprecipitation and spray drying/calcining methods have been used in the laboratory to produce homogeneous, reactive ceramic powders. Hot pressing and sintering at temperatures from 1000 to 11000C result in waste form products with greater than 97% of theoretical density. Hot isostatic pressing has recently been implemented as a processing alternative. Characterization of waste-form mineralogy has been done by means of XRD, SEM, and electron microprobe. Leaching of SYNROC D samples is currently being carried out. Assessment of radiation damage effects and physical properties of SYNROC D will commence in FY81

  5. Application of Defense Technology Commonly Used in Boxing Match

    Institute of Scientific and Technical Information of China (English)

    Zhixiao Li[1; Jianjun Liu[2

    2015-01-01

    Boxing defense technology is a kind of techniques to prevent the opponent from attacking successfully. Boxing is a kind of sports that needs close cooperation between attack and defense. Attack is used for defense, where there is no attack, there will be no defense, and vice versa. Defense technology is the foundation of attack technology, therefore, defense is of vital importance in boxing match.

  6. Antibacterial activity of resin rich plant extracts

    Directory of Open Access Journals (Sweden)

    Mohd Shuaib

    2013-01-01

    Full Text Available Background: The in vitro antibacterial activity of resin rich methanolic extracts (RRMEs of Commiphora myrrha, Operculina turpethum, and Pinus roxburghii. Materials and Methods: Different concentration were studied by agar-well diffusion method against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Enterococcus faecalis and Gram-negative bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysenteriae. Results: Among all the bacterial strains tested, E. faecalis was most sensitive and S. typhi was resistant to C. myrrha and P. roxburghii. The extracts of O. turpethum were active against all tested strains in which B. subtilis and S. aureus were the most sensitive. Conclusion: This suggested that the antibacterial activity of RRMEs of O. turpethum was more than C. myrrha and P. roxburghii. This probably explains the potential of these plants against a number of infections caused by bacterial strains tested.

  7. Diversity and antibacterial activity of phyllosticta species

    Directory of Open Access Journals (Sweden)

    E. Chukeatirote

    2015-01-01

    Full Text Available Phyllosticta fungi are widely distributed and appear to have different lifestyles. Although some Phyllosticta species are known to cause plant diseases, others are useful due to their bioactive metabolites. In this study, we screened and isolated the Phyllosticta fungi from several plant specimens. In total, 67 Phyllosticta isolates were identified based on their distinct morphological characteristics. Of these, 18 isolates were pathogens and 49 isolates were endophytes. Besides, 61 isolates (91% were identified as P. capitalensis indicating its widespread distribution. Thirty Phyllosticta isolates were then selected for studying their antibacterial activity. For this, the fungal strains were cultured in potato dextrose broth and cultivated at 27 C for 2 weeks. The fungal mycelia were removed and the culture supernatants were extracted using ethyl acetate. Antibacterial activity screening was then carried out using an agar disc diffusion assay. Our data showed that most Phyllosticta crude extracts (87% were active and could inhibit at least one of the testing bacteria.

  8. Light-activated polymethylmethacrylate nanofibers with antibacterial activity.

    Science.gov (United States)

    Elashnikov, Roman; Lyutakov, Oleksiy; Ulbrich, Pavel; Svorcik, Vaclav

    2016-07-01

    The creation of an antibacterial material with triggerable properties enables us to avoid the overuse or misuse of antibacterial substances and, thus, prevent the emergence of resistant bacterial strains. As a potential light-activated antibacterial material, polymethylmethacrylate (PMMA) nanofibers doped with silver nanoparticles (AgNPs) and meso-tetraphenylporphyrin (TPP) were prepared by electrospinning. TPP was chosen as an effectively reactive oxygen species (ROS) producer. Antibacterial tests on Staphylococcus epidermidis (S. epidermidis) and Enterococcus faecalis (E. faecalis) showed the excellent light-triggerable antibacterial activity of the doped materials. Upon light irradiation at the wavelength corresponding to the TPP absorption peak (405nm), antibacterial activity dramatically increased, mostly due to the release of AgNPs from the polymer matrix. Furthermore, under prolonged light irradiation, the AgNPs/TPP/PMMA nanofibers, displayed enhanced longevity and photothermal stability. Thus, our results suggest that the proposed material is a promising option for the photodynamic inactivation of bacteria. PMID:27127048

  9. Nrf2 and cardiovascular defense.

    Science.gov (United States)

    Howden, Reuben

    2013-01-01

    The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  10. Nrf2 and Cardiovascular Defense

    Directory of Open Access Journals (Sweden)

    Reuben Howden

    2013-01-01

    Full Text Available The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E 2-related factor 2 (Nrf2, regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis. The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  11. Defense mutualisms enhance plant diversification.

    Science.gov (United States)

    Weber, Marjorie G; Agrawal, Anurag A

    2014-11-18

    The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity.

  12. Antibacterial biodegradable Mg-Ag alloys

    Directory of Open Access Journals (Sweden)

    D Tie

    2013-06-01

    Full Text Available The use of magnesium alloys as degradable metals for biomedical applications is a topic of ongoing research and the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed as implant materials to combine the favourable properties of magnesium with the well-known antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag that contain 1.87 %, 3.82 % and 6.00 % silver by weight, respectively, were cast and processed with solution (T4 and aging (T6 heat treatment.The metallurgical analysis and phase identification showed that all alloys contained Mg4Ag as the dominant β phase. After heat treatment, the mechanical properties of all Mg-Ag alloys were significantly improved and the corrosion rate was also significantly reduced, due to presence of silver. Mg(OH2 and MgO present the main magnesium corrosion products, while AgCl was found as the corresponding primary silver corrosion product. Immersion tests, under cell culture conditions, demonstrated that the silver content did not significantly shift the pH and magnesium ion release. In vitro tests, with both primary osteoblasts and cell lines (MG63, RAW 264.7, revealed that Mg-Ag alloys show negligible cytotoxicity and sound cytocompatibility. Antibacterial assays, performed in a dynamic bioreactor system, proved that the alloys reduce the viability of two common pathogenic bacteria, Staphylococcus aureus (DSMZ 20231 and Staphylococcus epidermidis (DSMZ 3269, and the results showed that the killing rate of the alloys against tested bacteria exceeded 90%. In summary, biodegradable Mg-Ag alloys are cytocompatible materials with adjustable mechanical and corrosion properties and show promising antibacterial activity, which indicates their potential as antibacterial biodegradable implant materials.

  13. Experimental antibacterial activity of selective cyclooxygenase antagonist

    Directory of Open Access Journals (Sweden)

    Hayder M. Al-kuraishy

    2013-08-01

    Full Text Available Background: From the history of the development of pharmaceutical compounds it is evident that any drug may have the possibility of possessing diverse functions and thus may have useful activity in completely different fields of medicine and different studies showed that newer antimicrobials have revealed antimicrobial action involved in the management of diseases of non-infectious etiology. This study was done to determine in vitro antibacterial activity of selected selective cyclooxygenase-2 inhibitor. Methods: Twenty two strains of gram positive and gram negative bacteria, which were isolated from skin and urinary tract infected patient. These bacteria were being cultured on specific optimal growth media. The antibacterial activity of selective COX-2 (meloxicam, celecoxib, valdecoxib and nimesulide. Inhibitors determined by measuring zone of inhibition and minimal inhibitory concentration (MIC. Results: Results showed that MIC of celecoxib and meloxicam in µg/ml was ranged from 5-80µg/ml on selected bacteria compared with negative control distilled water (D.W ,valdecoxib was 80-160µg/ml, while and nimesulide was ranged from 5-40 µg/ml .All the selected bacteria were showed sensitivity for all coxib used in this experimental study except Pseudomonas aeruginosa which showed resistant to meloxicam and valdecoxib, Klebsiella pneumoniae resist to nimesulide while Staphylococcus aureus was resist to valdecoxib. The smaller zone of inhibition showed by valdecoxib and celecoxib which was 3mm against Klebsiella pneumoniae, while the larger zone of inhibition showed by nimesulide which was 26mm against Escherichia coli. Conclusions: In conclusion selective cyclooxygenase (cox-2 inhibitor possesses antibacterial activity this is especially for nimesulide and little by valdecoxib. Escherichia coli are sensitive bacteria to all coxib. Consequently; coxib may be regarded as anti-inflammatory and antibacterial agent especially for urinary tract

  14. Honey: its medicinal property and antibacterial activity

    OpenAIRE

    Mandal, Manisha Deb; Mandal, Shyamapada

    2011-01-01

    Indeed, medicinal importance of honey has been documented in the world's oldest medical literatures, and since the ancient times, it has been known to possess antimicrobial property as well as wound-healing activity. The healing property of honey is due to the fact that it offers antibacterial activity, maintains a moist wound condition, and its high viscosity helps to provide a protective barrier to prevent infection. Its immunomodulatory property is relevant to wound repair too. The antimic...

  15. Actinopyga lecanora Hydrolysates as Natural Antibacterial Agents

    OpenAIRE

    Raheleh Ghanbari; Afshin Ebrahimpour; Azizah Abdul-Hamid; Amin Ismail; Nazamid Saari

    2012-01-01

    Actinopyga lecanora, a type of sea cucumber commonly known as stone fish with relatively high protein content, was explored as raw material for bioactive peptides production. Six proteolytic enzymes, namely alcalase, papain, pepsin, trypsin, bromelain and flavourzyme were used to hydrolyze A. lecanora at different times and their respective degrees of hydrolysis (DH) were calculated. Subsequently, antibacterial activity of the A. lecanora hydrolysates, against some common pathogenic Gram posi...

  16. Chemical Composition and Antibacterial Effects of

    OpenAIRE

    SS Saei Dehkordi; H Tajik; Moradi, M; A Jafari Dehkordi; Ghasemi, S.

    2009-01-01

    Introduction & Objective: Rosmarinus officinalis L. as a member of the Lamiaceae family and lysozyme as a natural antibacterial agent is important in food microbiology, because of its characteristics. The aim of the present study was to determine the chemical composition and anti-listerial activity of Rosmarinus officinalis essential oil (REO) alone and in combination with lysozyme for enhancement of anti-listerial activity of both substances. Materials & Methods: Rosmarinus officinalis ...

  17. Investigation of the antibacterial activity of pioglitazone

    Directory of Open Access Journals (Sweden)

    Alzoubi KH

    2011-09-01

    Full Text Available Majed M Masadeh1, Nizar M Mhaidat2, Sayer I Al-Azzam2, Karem H Alzoubi21Department of Pharmaceutical Technology; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanPurpose: To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae and Gram-negative (Escherichia coli and Klebsiella pneumoniae bacteria.Methods: Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC of pioglitazone was measured according to the broth micro incubation standard method.Results: Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 µM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 ± 3.87 mg/L to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 ± 3.77 mg/L and MIC = 62.5 ± 4.14 mg/L, respectively. Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 µM before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae.Conclusion: These results indicate the possibility of a new and potentially important pioglitazone effect and the authors’ ongoing studies aim to illustrate the mechanism(s by which this antibacterial effect is induced.Keywords: pioglitazone, susceptibility testing, antibiotics, diabetes 

  18. [Current status and further prospects of dental resin-based materials with antibacterial properties].

    Science.gov (United States)

    Shi, X; Lu, H B; Mao, J; Gong, S Q

    2016-09-01

    The mode of dental antibacterial resin-based materials can be divided into two types, namely, single and combined antibacterial mode. With regard to single antibacterial mode, only one kind of antibacterial agent is added into the resin, which can be released or act as contacting antibacterial agent. The single mode resin has limitation in sterilization methods and effect. As for combined antibacterial mode, it is a combination of different types of biocides and thus maximizes the sterilizing effect, including the releasing antibacterial agent incorporated with the contacting antibacterial agent or antibacterial agents combined with calcium compound possessing biological mineralization function. In this paper, current status and further prospects of dental resin-based materials with antibacterial properties are reviewed from the perspectives of single and combined antibacterial modes to provide guidance for dental antibacterial resin material research.

  19. Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

    Directory of Open Access Journals (Sweden)

    Workalemahu M. Berhanu

    2012-07-01

    Full Text Available The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium.

  20. Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

    Science.gov (United States)

    Berhanu, Workalemahu M; Ibrahim, Mohamed A; Pillai, Girinath G; Oliferenko, Alexander A; Khelashvili, Levan; Jabeen, Farukh; Mirza, Bushra; Ansari, Farzana Latif; ul-Haq, Ihsan; El-Feky, Said A

    2012-01-01

    Summary The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium. PMID:23019443

  1. The antibacterial paradox: essential drugs, effectiveness, and cost.

    OpenAIRE

    Fasehun, F.

    1999-01-01

    The concept proposed by WHO of an essential drugs list that should comprise drugs corresponding to the health needs of the majority of the people has been embraced by countries, which have adapted it to their needs. In this study, the essential antibacterial drug lists of 16 countries chosen from the six WHO regions are reviewed. Most of these countries include 73% of WHO-recommended essential antibacterials on their lists. However, most are lacking reserve antibacterials, and even some main ...

  2. EVALUATION OF ANTIBACTERIAL ACTIVITY OF CAFFEINE

    Directory of Open Access Journals (Sweden)

    Pawar Pruthviraj

    2011-04-01

    Full Text Available The present study was carried out with water soluble portion and pure solvent of the acetone, ethanol, methanol, acetonitrile, water extracts of leaves and leaf buds of Camellia sinensis (green tea, and beans of Coffea arabica (coffee. Caffeine (3,7-dihydro-1, 3,7-trimethyl-1H-purine-2,6-dione was isolated from both plants using a liquid-liquid extraction method, detected on thin layer chromatography (TLC plates in comparison with standard caffeine, which served as a positive control. After performing the gross behavioral study, the Antibacterial activity was evaluated against Gram-negative bacteria included; Escherichia coli, Proteus mirabilis, Klebsiella pneumonia and Pseudomonas aeruginosa Both compounds at a concentration of 2 mg/ml showed similar antibacterial activities against all tested bacteria, except for P. mirabilis, and the highest inhibitory effect was observed against P. aeruginosa using a modified agar diffusion method. The minimal inhibitory concentration (MIC of caffeine was determined using a broth microdilution method in 96 multi-well microtitre plates. MIC values ranged from 65.5 to 250.0 µg/ml for the caffeine isolated from coffee and 65.5 to 500.0 µg/ml for green tea caffeine. Combination results showed additive effects against most pathogenic bacteria especially for P. aeruginosa, using both antibacterial assays.

  3. Antibacterial Effects of Silver Loaded Hydroxyapatite

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The antibacterial capability of silver loaded hydroxyapatite(HA-Ag) in both poor nutrient phosphate buffer saline solution(PBS,pH=7.4)and nutrient rich medium,which represented two kinds of typical conditions in real life,was evaluated respectively using Escherichia coli as a model.At 0.4 mg/mL in PBS solution containing an initial cell concentration of 106/mL,HA-Ag killed all the E.coli cells in the PBS solution within 4.5 h.In a nutrient rich medium containing a cell concentration of 107/mL,HA-Ag exhibited a remarkable inhibitory effect of E.coli cells.The maximum specific growth rate in the medium containing 3 mg/mL HA-Ag was only 0.292, 26% of that in a control sample which was 1.116,and the viable cell concentration in the former HA-Ag medium was just 40% of that in the control.As a safe antibacterial agent,HA-Ag powder demonstrated antibacterial efforts both in poor nutrient and in nutrient rich environment.It seems that the HA-Ag compound hold a lot of promises for practical applications.

  4. The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

    Science.gov (United States)

    Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

    2015-07-01

    Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

  5. Consequences of increased antibacterial consumption and change in pattern of antibacterial use in Danish hospitals

    DEFF Research Database (Denmark)

    Jensen, Ulrich S; Skjøt-Rasmussen, Line; Olsen, Stefan S;

    2009-01-01

    OBJECTIVES: Antibacterial consumption is increasing in many countries around the world, and it is increasingly recognized as the main reason for the emergence of resistance. This study was implemented to analyse antibacterial consumption in public hospitals in Denmark during 2001-07 as a follow......-up on a prior analysis and furthermore, to investigate the consequences of the occurrence of resistance. METHODS: National data on the consumption of antibacterials for systemic use in Danish public hospitals were obtained from 2001 through 2007. Consumption data were compared with antimicrobial resistance...... in all isolates recorded from either blood samples (Escherichia coli and Klebsiella pneumoniae) or urine samples (E. coli) submitted for susceptibility testing to the participating Departments of Clinical Microbiology during 2001-07. RESULTS: The consumption of combinations of penicillins including beta...

  6. Analysis of gene expression from the Wolbachia genome of a filarial nematode supports both metabolic and defensive roles within the symbiosis.

    Science.gov (United States)

    Darby, Alistair C; Armstrong, Stuart D; Bah, Germanus S; Kaur, Gaganjot; Hughes, Margaret A; Kay, Suzanne M; Koldkjær, Pia; Rainbow, Lucille; Radford, Alan D; Blaxter, Mark L; Tanya, Vincent N; Trees, Alexander J; Cordaux, Richard; Wastling, Jonathan M; Makepeace, Benjamin L

    2012-12-01

    The α-proteobacterium Wolbachia is probably the most prevalent, vertically transmitted symbiont on Earth. In contrast with its wide distribution in arthropods, Wolbachia is restricted to one family of animal-parasitic nematodes, the Onchocercidae. This includes filarial pathogens such as Onchocerca volvulus, the cause of human onchocerciasis, or river blindness. The symbiosis between filariae and Wolbachia is obligate, although the basis of this dependency is not fully understood. Previous studies suggested that Wolbachia may provision metabolites (e.g., haem, riboflavin, and nucleotides) and/or contribute to immune defense. Importantly, Wolbachia is restricted to somatic tissues in adult male worms, whereas females also harbor bacteria in the germline. We sought to characterize the nature of the symbiosis between Wolbachia and O. ochengi, a bovine parasite representing the closest relative of O. volvulus. First, we sequenced the complete genome of Wolbachia strain wOo, which revealed an inability to synthesize riboflavin de novo. Using RNA-seq, we also generated endobacterial transcriptomes from male soma and female germline. In the soma, transcripts for membrane transport and respiration were up-regulated, while the gonad exhibited enrichment for DNA replication and translation. The most abundant Wolbachia proteins, as determined by geLC-MS, included ligands for mammalian Toll-like receptors. Enzymes involved in nucleotide synthesis were dominant among metabolism-related proteins, whereas the haem biosynthetic pathway was poorly represented. We conclude that Wolbachia may have a mitochondrion-like function in the soma, generating ATP for its host. Moreover, the abundance of immunogenic proteins in wOo suggests a role in diverting the immune system toward an ineffective antibacterial response. PMID:22919073

  7. Towards Identify Selective Antibacterial Peptides Based on Abstracts Meaning

    Science.gov (United States)

    Barbosa-Santillán, Liliana I.; Sánchez-Escobar, Juan J.; Calixto-Romo, M. Angeles; Barbosa-Santillán, Luis F.

    2016-01-01

    We present an Identify Selective Antibacterial Peptides (ISAP) approach based on abstracts meaning. Laboratories and researchers have significantly increased the report of their discoveries related to antibacterial peptides in primary publications. It is important to find antibacterial peptides that have been reported in primary publications because they can produce antibiotics of different generations that attack and destroy the bacteria. Unfortunately, researchers used heterogeneous forms of natural language to describe their discoveries (sometimes without the sequence of the peptides). Thus, we propose that learning the words meaning instead of the antibacterial peptides sequence is possible to identify and predict antibacterial peptides reported in the PubMed engine. The ISAP approach consists of two stages: training and discovering. ISAP founds that the 35% of the abstracts sample had antibacterial peptides and we tested in the updated Antimicrobial Peptide Database 2 (APD2). ISAP predicted that 45% of the abstracts had antibacterial peptides. That is, ISAP found that 810 antibacterial peptides were not classified like that, so they are not reported in APD2. As a result, this new search tool would complement the APD2 with a set of peptides that are candidates to be antibacterial. Finally, 20% of the abstracts were not semantic related to APD2. PMID:27366202

  8. Antibacterial Resistance in African Catfish Aquaculture: a Review

    Directory of Open Access Journals (Sweden)

    Madubuike U. ANYANWU

    2016-03-01

    Full Text Available Antibacterial resistance (AR is currently one of the greatest threats to mankind as it constitutes health crisis. Extensive use of antibacterial agents in human and veterinary medicine, and farm crops have resulted in emergence of antibacterial-resistant organisms in different environmental settings including aquaculture. Antibacterial resistance in aquaculture is a serious global concern because antibacterial resistance genes (ARGs can be transferred easily from aquaculture setting to other ecosystems and the food chain. African catfish (ACF aquaculture has increased at a phenomenal rate through a continuous process of intensification, expansion and diversification. Risk of bacterial diseases has also increased and consequently there is increased use of antibacterial agents for treatment. Antibacterial resistance in ACF aquaculture has huge impact on the food chain and thus represents risk to public and animal health. In “one health” approach of curbing AR, knowledge of the sources, mechanisms and magnitude of AR in ACF aquaculture and its potential impact on the food chain is important in designing and prioritizing monitoring programs that may generate data that would be relevant for performing quantitative risk assessments, implementation of antibacterial stewardship plans, and developing effective treatment strategies for the control of ACF disease and reducing risk to public health. This review provides insight on the sources, mechanisms, prevalence and impact of antibacterial resistance in ACF aquaculture environment, a setting where the impact of AR is neglected or underestimated.

  9. Towards Identify Selective Antibacterial Peptides Based on Abstracts Meaning.

    Science.gov (United States)

    Barbosa-Santillán, Liliana I; Sánchez-Escobar, Juan J; Calixto-Romo, M Angeles; Barbosa-Santillán, Luis F

    2016-01-01

    We present an Identify Selective Antibacterial Peptides (ISAP) approach based on abstracts meaning. Laboratories and researchers have significantly increased the report of their discoveries related to antibacterial peptides in primary publications. It is important to find antibacterial peptides that have been reported in primary publications because they can produce antibiotics of different generations that attack and destroy the bacteria. Unfortunately, researchers used heterogeneous forms of natural language to describe their discoveries (sometimes without the sequence of the peptides). Thus, we propose that learning the words meaning instead of the antibacterial peptides sequence is possible to identify and predict antibacterial peptides reported in the PubMed engine. The ISAP approach consists of two stages: training and discovering. ISAP founds that the 35% of the abstracts sample had antibacterial peptides and we tested in the updated Antimicrobial Peptide Database 2 (APD2). ISAP predicted that 45% of the abstracts had antibacterial peptides. That is, ISAP found that 810 antibacterial peptides were not classified like that, so they are not reported in APD2. As a result, this new search tool would complement the APD2 with a set of peptides that are candidates to be antibacterial. Finally, 20% of the abstracts were not semantic related to APD2. PMID:27366202

  10. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine

    Directory of Open Access Journals (Sweden)

    Ying Gu

    2012-10-01

    Full Text Available In 1983, it was first reported that tetracyclines (TCs can modulate the host response, including (but not limited to inhibition of pathologic matrix metalloproteinase (MMP activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD and compositions (chemically modified tetracyclines; CMTs of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS. In addition, this review discusses a number of clinical studies, some up to 2 years’ duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.

  11. THE DEFENSE PLANNING SYSTEMS AND THEIR IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Laszlo STICZ

    2010-01-01

    Full Text Available Defense planning in the Alliance is a fundamental element of the arrangements which enable its member countries to enjoy the crucial political, military and resource advantages of collective defense and other common military efforts to enhance security and stability. In this respect, the aim of this paper is to outline the role of the Armed Forces and the specific processes aiming to achieve the ultimate goal of a nation regarding national security, with focus on defense planning and the PDPS.

  12. Department of Defense, Deployment Health Clinical Center

    Science.gov (United States)

    ... Psychological Health Policy Library Search psychological health and deployment-related policies and directives, including service-specific policies, published by the Defense Department, Congress ...

  13. SELF-DEFENSE IN KARABAKH CONFLICT?

    Directory of Open Access Journals (Sweden)

    Saeed Bagheri

    2015-01-01

    Full Text Available Use of force is one of the principles of international law which has been banned by the UN Charter and modern constitutions. However, since the enforcement of the UN Charter, self-defense has become the preferred excuse for states to justify their use of force. But applying self-defense requires some conditions. Immediacy is one of the important conditions of self-defense. Immediacy defined as the time span between armed attacks and reaction to it, is the main discourse. This condition requires self defense immediately after the armed conflict or during a rational time span since its occurance.In this respect, the emerging Karabakh Conflict between Armenia and Azerbaijan in the 1990s is important. After Armenia’s armed attacks, Azerbaijan has acted within the scope of legitimate self-defense. But in accordance with UN Security Council cease-fire resolution Azerbaijan has suspended its self-defense actions. However, today, still twenty percent of Azerbaijani territory is still under Armenian occupation. Accordingly, after a long time the validity of Azerbaijan’s right to legitimate self-defense is still subject to arguments.In this article, by comparing two different approaches (strict and board interpretation approaches on the temporal link between the measures of self-defense and the armed attacks (immediacy, the temporal link between the self-defense countermeasures of Azerbaijan and armed attacks by Armenia in Karabakh Conflict will be examined.

  14. Takedown Defenses of Russian Systema

    Directory of Open Access Journals (Sweden)

    Kevin R. Secours

    2012-07-01

    Full Text Available The continuing popularity of mixed martial arts (MMA events has motivated many martial artists to cross train in grappling disciplines. While largely beneficial for the arts as a whole, many practitioners have nevertheless integrated grappling strategies without considering whether or not their applications are simply sportive or appropriate for self-defense tactics. In this article, I will examine some historical perspectives on the role of grappling on the battlefield from published literature and consider the evidence left to us through historical texts and artwork. Based on over 20 years experience in the grappling arts, I will attempt to show that ground fighting and grappling are necessary components of a complete tactical arsenal, while carefully illustrating the difference in street tactics. I will place specific emphasis on the role of defending the takedown in a modern survival scenario, giving particular attention to the approach employed by the Russian art of Systema.

  15. Low power unattended defense reactor

    International Nuclear Information System (INIS)

    A small, low power, passive, nuclear reactor electric power supply has been designed for unattended defense applications. Through innovative utilization of existing proven technologies and components, a highly reliable, walk-away safe design has been obtained. Operating at a thermal power level of 200 kWt, the reactor uses low enrichment uranium fuel in a graphite block core to generate heat that is transferred through heat pipes to a thermoelectric (TE) converter. Waste heat is removed from the TEs by circulation of ambient air. Because such a power supply offers the promise of minimal operation and maintenance (O and M) costs as well as no fuel logistics, it is particularly attractive for remote, unattended applications such as the North Warning System

  16. Alarm Odor Compounds of the Brown Marmorated Stink Bug Exhibit Antibacterial Activity

    Science.gov (United States)

    Sagun, Steven; Collins, Elliot; Martin, Caleb; Nolan, E Joseph; Horzempa, Joseph

    2016-01-01

    Some insects release scented compounds as a defense against predators that also exhibit antimicrobial activity. Trans-2-octenal and trans-2-decenal are the major alarm aldehydes responsible for the scent of Halyomorpha halys, the brown marmorated stink bug. Previous research has shown these aldehydes are antifungal and produce an antipredatory effect, but have never been tested for antibacterial activity. We hypothesized that these compounds functioned similarly to the analogous multifunctional action of earwig compounds, so we tested whether these aldehydes could inhibit the growth of bacteria. Disk diffusion assays indicated that these aldehydes significantly inhibited the growth of Methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, in vitro. Moreover, mealworm beetles (Tenebrio molitor) coated in stink bug aldehydes showed a substantial reduction in bacterial colonization compared to vehicle-treated insects. These results suggest that brown marmorated stinkbug aldehydes are indeed antibacterial agents and serve a multifunctional role for this insect. Therefore, stinkbug aldehydes may have potential for use as chemical antimicrobials.

  17. A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells.

    Science.gov (United States)

    Chiou, Shean-Jaw; Wang, Chan-Chi; Tseng, Yan-Shen; Lee, Yen-Jung; Chen, Shih-Chieh; Chou, Chi-Hsien; Chuang, Lea-Yea; Hong, Yi-Ren; Lu, Chi-Yu; Chiu, Chien-Chih; Chignard, Michel

    2016-01-01

    We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration. PMID:27503241

  18. An Empirical Investigation of Defense Interpretation Depth, Defensive Functioning, and Alliance Strength in Psychodynamic Psychotherapy.

    Science.gov (United States)

    Petraglia, Jonathan; Bhatia, Maneet; De Roten, Yves; Despland, Jean-Nicolas; Drapeau, Martin

    2015-01-01

    The present study examined the relationship between depth of defense interpretations by therapists, and patient defensive functioning, on the therapeutic alliance in a sample of 36 patients undergoing short-term dynamic psychotherapy. Defense interpretation depth was defined as the degree to which therapist interpretations contained information regarding the motivation for patient defenses and historical origins of the defensive processes (Greensen, 1967). Mean depth of interpretation was compared between sessions that were identified beforehand as either high-alliance or low-alliance sessions using the Helping Alliance Questionnaire (HAq-II: Luborsky et al., 1996). Results indicated that defensive functioning was correlated to defense interpretation depth in low-alliance sessions. Moreover, mean depth of interpretation was also higher in low-alliance sessions, pointing to the possible "destabilizing" effects that these interpretations may have on both defensive functioning and the therapeutic alliance. These results are discussed within the context of previous studies of therapeutic technique in dynamic psychotherapy.

  19. A viral suppressor protein inhibits host RNA silencing by hooking up with Argonautes

    KAUST Repository

    Jin, Hailing

    2010-05-01

    RNA viruses are particularly vulnerable to RNAi-based defenses in the host, and thus have evolved specific proteins, known as viral suppressors of RNA silencing (VSRs), as a counterdefense. In this issue of Genes & Development, Azevedo and colleagues (pp. 904-915) discovered that P38, the VSR of Turnip crinkle virus, uses its glycine/tryptophane (GW) motifs as an ARGONAUTE (AGO) hook to attract and disarm the host\\'s essential effector of RNA silencing. Several GW motif-containing cellular proteins are known to be important partners of AGOs in RNA silencing effector complexes in yeast, plants, and animals. The GW motif appears to be a versatile and effective tool for regulating the activities of RNA silencing pathways, and the use of GW mimicry to compete for and inhibit host AGOs may be a strategy used by many pathogens to counteract host RNAi-based defenses. © 2010 by Cold Spring Harbor Laboratory Press.

  20. Investment in defense and cost of predator-induced defense along a resource gradient

    OpenAIRE

    Steiner, U K

    2007-01-01

    An organism’s investment in different traits to reduce predation is determined by the Fitness benefit of the defense relative to the Fitness costs associated with the allocation of time and resources to the defense. Inherent tradeoffs in time and resource allocation should result in differential investment in defense along a resource gradient, but competing models predict different patterns of investment. There are currently insuffcient empirical data on changes in investment in defensive tra...

  1. 75 FR 3210 - Renewal of Department of Defense Federal Advisory Committee; Defense Business Board

    Science.gov (United States)

    2010-01-20

    ... sector corporations or entities and a wealth of top-level, global business experience in the areas of... of the Secretary Renewal of Department of Defense Federal Advisory Committee; Defense Business Board... gives notice that it is renewing the charter for the Defense Business Board (hereafter referred to...

  2. 75 FR 15695 - Renewal of Department of Defense Federal Advisory Committee; Board of Visitors National Defense...

    Science.gov (United States)

    2010-03-30

    ... Defense gives notice that it is renewing the charter for the Board of Visitors National Defense University (hereafter referred to as the Board). FOR FURTHER INFORMATION CONTACT: Jim Freeman, Deputy Committee... of the Secretary Renewal of Department of Defense Federal Advisory Committee; Board of...

  3. 75 FR 13093 - Renewal of Department of Defense Federal Advisory Committee; Defense Acquisition University Board...

    Science.gov (United States)

    2010-03-18

    ... University Board of Visitors AGENCY: Department of Defense (DoD). ACTION: Renewal of Federal advisory... amended), and 41 CFR 102-3.50(c), the Department of Defense gives notice that it is renewing the charter for the Defense Acquisition University Board of Visitors (hereafter referred to as the Board)....

  4. Strategic Defense Initiative: Splendid Defense or Pipe Dream? Headline Series No. 275.

    Science.gov (United States)

    Armstrong, Scott; Grier, Peter

    This pamphlet presents a discussion of the various components of President Reagan's Strategic Defense Initiative (SDI) including the problem of pulling together various new technologies into an effective defensive system and the politics of the so-called "star wars" system. An important part of the defense initiative is the "layered" defense…

  5. 76 FR 11361 - Defense Federal Acquisition Regulation Supplement; Preservation of Tooling for Major Defense...

    Science.gov (United States)

    2011-03-02

    ... contractor to ``have a system to manage (control, use, preserve, protect, repair, and maintain) Government... internal DoD procedural matters. Specifically, this implementation of section 815 of the National Defense... Defense Acquisition Regulations System 48 CFR Part 207 RIN 0750-AG45 Defense Federal...

  6. Competition for Manganese at the Host-Pathogen Interface.

    Science.gov (United States)

    Kelliher, J L; Kehl-Fie, T E

    2016-01-01

    Transition metals such as manganese are essential nutrients for both pathogen and host. Vertebrates exploit this necessity to combat invading microbes by restricting access to these critical nutrients, a defense known as nutritional immunity. During infection, the host uses several mechanisms to impose manganese limitation. These include removal of manganese from the phagolysosome, sequestration of extracellular manganese, and utilization of other metals to prevent bacterial acquisition of manganese. In order to cause disease, pathogens employ a variety of mechanisms that enable them to adapt to and counter nutritional immunity. These adaptations include, but are likely not limited to, manganese-sensing regulators and high-affinity manganese transporters. Even though successful pathogens can overcome host-imposed manganese starvation, this defense inhibits manganese-dependent processes, reducing the ability of these microbes to cause disease. While the full impact of host-imposed manganese starvation on bacteria is unknown, critical bacterial virulence factors such as superoxide dismutases are inhibited. This chapter will review the factors involved in the competition for manganese at the host-pathogen interface and discuss the impact that limiting the availability of this metal has on invading bacteria. PMID:27571690

  7. Cationic amphiphilic non-hemolytic polyacrylates with superior antibacterial activity.

    Science.gov (United States)

    Punia, Ashish; He, Edward; Lee, Kevin; Banerjee, Probal; Yang, Nan-Loh

    2014-07-01

    Acrylic copolymers with appropriate compositions of counits having cationic charge with 2-carbon and 6-carbon spacer arms can show superior antibacterial activities with concomitant very low hemolytic effect. These amphiphilic copolymers represent one of the most promising synthetic polymer antibacterial systems reported. PMID:24854366

  8. Two Novel Antibacterial Flavonoids from Myrsine Africana L.

    Institute of Scientific and Technical Information of China (English)

    KANG,Lu; ZHOU,Jian-Xia; SHEN,Zheng-Wu

    2007-01-01

    Two novel flavonoids, myrsininone A (1), an isoflavone and myrsininone B (2), a flavanone, with very strong antibacterial activities, were isolated from the stems of Myrsine africana L. Their structures were elucidated by extensive spectroscopic analyses. The antibacterial activities were determined by modified Resazuric MIC methods.

  9. Methyl carnosate, an antibacterial diterpene isolated from Salvia officinalis leaves.

    Science.gov (United States)

    Climati, Elisa; Mastrogiovanni, Fabio; Valeri, Maria; Salvini, Laura; Bonechi, Claudia; Mamadalieva, Nilufar Zokirzhonovna; Egamberdieva, Dilfuza; Taddei, Anna Rita; Tiezzi, Antonio

    2013-04-01

    Ethanolic extracts of Salvia officinalis leaves demonstrated antibacterial activity against Bacillus cereus. Fractionation of the extracts led to the isolation of the most active antibacterial compound, which, from spectroscopic and LC-MS evidence, was proved to be the diterpene, methyl carnosate.

  10. Facilitating Antibacterial Drug Development in a Time of Great Need.

    Science.gov (United States)

    Cox, Edward; Cavaleri, Marco; Eichler, Hans-Georg; Woodcock, Janet; Borio, Luciana

    2016-08-15

    The continued development of new antibacterial drugs is critical to meet patient and public health needs. In this editorial, authors from the US Food and Drug Administration and European Medicines Agency reflect on the role of public-private partnerships and the development of clinical trials networks as agents to guide and perform quality studies of antibacterial drugs. PMID:27481949

  11. Antibacterial activities of PHU - AgNO{sub 3} nanocomposite

    Energy Technology Data Exchange (ETDEWEB)

    Panzaru, Carmen; Danciu, M; Mihailovici, Maria-Sultana [' Gr.T.Popa' University of Medicine and Pharmacy, Iasi (Romania)], E-mail: carmenpanzaru@yahoo.com; Ciobanu, C [' Petru Poni' Institute of Macromolecular Chemistry, Iasi (Romania)

    2009-05-01

    Objective was to characterize the antibacterial action for six combination of PHU-AgNO{sub 3} synthesized in 'Petru Poni' Institute of Macromolecular Chemistry, Iasi, Romania. The advantages of Ag nanoparticles are durability, heat resistant, low toxicity. Silver is known for its antibacterial qualities for a long time and has been used in medicine in topical treatment.

  12. Antibacterial activity of mushroom Osmoporus odoratus

    OpenAIRE

    Sivakumar R; Vetrichelvan T; Rajendran N; Devi M; Sundaramoorthi K; Shankar ASK; Shanmugam S

    2006-01-01

    The petroleum ether, chloroform, acetone and water extracts of mushroom Osmoporus odoratus were selected for examine the antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa by disc diffusion method using Muller Hinton agar media. And the extracts were compared with that of standard ampicillin (30 µg) and chloramphenicol (30 µg). The water extract alone showed antibacterial activity aga...

  13. Soluble Eggshell Mebrane Protein:Antibacterial Property and Biodegradability

    Institute of Scientific and Technical Information of China (English)

    YI Feng; YU Jian; LI Qiang; GUO Zhaoxia

    2007-01-01

    The antibacterial property and biodegradability of soluble eggshell membrane protein (SEP)are reported. Unlike the natural eggshell membrane (ESM), SEP does not possess antibacterial property against E.coli. The biodegradation tests with trypsin show that both ESM and SEP are biodegradable.

  14. Defensive externality and blame projection following failure.

    Science.gov (United States)

    Hochreich, D J

    1975-09-01

    This study focuses upon the relationship between internal-external control and defensive blame projection. Trust was used as a moderator variable for making differential predictions concerning the behavior of two subgroups of externals: defensive externals, whose externality is presumed to reflect primarily a verbal technique of defense, and congruent externals, whose externality reflects a more genuine belief that most outcomes are determined by forces beyond their personal control. As predicted, defensive externals showed a stronger tendency than did congruent externals and internals to resort to blame projection following failure at an achievement task. There were no group differences in attribution following task success. Defensive externals were found to be more responsive to negative feedback than were congruent externals.

  15. Primitive defenses: cognitive aspects and therapeutic handling.

    Science.gov (United States)

    Groh, L S

    In this paper the primitive defenses first described by Melanie Klein under the label of "schizoid mechanisms" are examined. The defenses considered are splitting the pathological uses of identification and projective identification, and the psychotic forms of denial. This examination is twofold: (1) the cognitive aspects of these defenses as described in terms of concepts developed by Jean Piaget; (2) concrete examples of the operation of these defenses during the treatment of schizophrenic patients are given and the effects of interventions based on the cognitive analysis are described. It is stressed that at times interventions, such as interpretation and confrontation, based on cognitive analysis, can temporarily and in some instances even permanently stop the operation of these defenses, allowing emotionally meaningful material to emerge which expedites the therapeutic process. PMID:7429737

  16. Cirrhosis-induced defects in innate pulmonary defenses against Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Vander Top Elizabeth A

    2007-10-01

    Full Text Available Abstract Background The risk of mortality from pneumonia caused by Streptococcus pneumoniae is increased in patients with cirrhosis. However, the specific pneumococcal virulence factors and host immune defects responsible for this finding have not been clearly established. This study used a cirrhotic rat model of pneumococcal pneumonia to identify defect(s in innate pulmonary defenses in the cirrhotic host and to determine the impact of the pneumococcal toxin pneumolysin on these defenses in the setting of severe cirrhosis. Results No cirrhosis-associated defects in mucociliary clearance of pneumococci were found in these studies, but early intrapulmonary killing of the organisms before the arrival of neutrophils was significantly impaired. This defect was exacerbated by pneumolysin production in cirrhotic but not in control rats. Neutrophil-mediated killing of a particularly virulent type 3 pneumococcal strain also was significantly diminished within the lungs of cirrhotic rats with ascites. Levels of lysozyme and complement component C3 were both significantly reduced in bronchoalveolar lavage fluid from cirrhotic rats. Finally, complement deposition was reduced on the surface of pneumococci recovered from the lungs of cirrhotic rats in comparison to organisms recovered from the lungs of control animals. Conclusion Increased mortality from pneumococcal pneumonia in this cirrhotic host is related to defects in both early pre-neutrophil- and later neutrophil-mediated pulmonary killing of the organisms. The fact that pneumolysin production impaired pre-neutrophil-mediated pneumococcal killing in cirrhotic but not control rats suggests that pneumolysin may be particularly detrimental to this defense mechanism in the severely cirrhotic host. The decrease in neutrophil-mediated killing of pneumococci within the lungs of the cirrhotic host is related to insufficient deposition of host proteins such as complement C3 on their surfaces. Pneumolysin

  17. Uncovering the transcriptional control of "Bartonella henselae" host adaptation factors

    OpenAIRE

    Québatte, Maxime

    2014-01-01

    A recurrent theme in bacterial pathogenicity is the understanding of the regulatory events necessary for a given pathogen to progress through its infection cycle while resisting the host defense mechanisms. This progression typically requires the coordinated expression of defined sub-portions of the virulence repertoire at the same time as others need to be tightly repressed or degraded. This so-called adaptive response is ultimately linked to the ability of the pathogen to sense its direct e...

  18. Antibacterial biodegradable Mg-Ag alloys

    OpenAIRE

    D Tie; F Feyerabend; W-D Müller; Schade, R; Liefeith, K; KU Kainer; Willumeit, R.

    2013-01-01

    The use of magnesium alloys as degradable metals for biomedical applications is a topic of ongoing research and the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed as implant materials to combine the favourable properties of magnesium with the well-known antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag that contain 1.87 %, 3.82 % and 6.00 % silver by weight, respectively, were cast and processed with solut...

  19. Antibacterial Mg-Ag biodegradable alloys

    OpenAIRE

    Tie, Di

    2013-01-01

    The use of magnesium alloys as degradable metals for biomedical applications is topic of ongoing research. As a further aspect, the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed to combine the favourable properties of magnesium with the wellknown antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag which contain 1.87%, 3.82% and 6.00% silver by weight respectively were casted and processed with solution and ...

  20. Synthesis and Antibacterial Activity of Thiophenes

    Directory of Open Access Journals (Sweden)

    Wedad M. Al-Adiwish

    2012-01-01

    Full Text Available 2-[Bis(methylthiomethylene]propanedinitrile 1a reacted in one-pot successively with piperidine, sodium sulfide, chloroacetonitrile, and potassium carbonate to afford 3-amino-5-(1-piperidinyl-2,4-thiophenedicarbonitrile 2a. Similar reaction using the last three reagents with ethyl 2-cyano-3,3-bis(methylthioacrylate 1b produced ethyl 4-amino-5-cyano-2-(methylthiothiophene-3-carboxylate 2b. The synthesized compounds were characterized by using FT-IR, 1H-NMR, 13C-NMR, and mass spectral data. Antibacterial activities of the synthesized compounds are also reported.

  1. Antioxidant and antibacterial properties of capsaicine microemulsions

    OpenAIRE

    CRISTIAN DIMA; GIGI COMAN; MIHAELA COTÂRLEŢ; PETRU ALEXE; ŞTEFAN DIMA

    2013-01-01

    The aim of this study was to prepare capsaicin microemulsions and to assess their antioxidant and antibacterial properties. Pseudoternare phase diagrams were made and were highlighted O/W/S/CoS weight ratios corresponding to microemulsion states. The oil phase (O) was soybean oil and for the aqueous phase (W) was used a mixture of water and glycerol in a ratio of 4:1 (wt/wt). As a surfactant (S) was used Tween 40 and cosurfactant (CoS) was ethanol in the mass ratio S:CoS = 2:1. Viscosimetr...

  2. Chemical and antibacterial constituents of Skimmia anquetelia.

    Science.gov (United States)

    Sharma, Rajni Kant; Negi, Devendra Singh; Gibbons, Simon; Otsuka, Hideaki

    2008-02-01

    Investigation of the leaves of Skimmia anquetelia (Rutaceae) led to the isolation of a new coumarin glucoside 7,8-dihdroxy-6-[3'-beta- D-glucopyranosyloxy-2'(xi)-hydroxy-3'-methylbutyl]-coumarin ( 1) together with five known coumarins: 6-(2,3-dihydroxy-3-methylbutyl)-7-methoxycoumarin ( 2), skimmin ( 3), osthol ( 4), esculetin ( 5) and scopuletin ( 6). The antibacterial activity of compounds 1 and 3 was also investigated against the plant bacterial pathogens Agrobacterium tumifaciens, Pseudomonas syringae and Pactobacterium carotovorum. Structures were determined on the basis of analyses of spectral evidence including 1D, 2 D NMR (COSY, HMQC, HMBC and NOESY) and mass spectroscopy. PMID:18240101

  3. Detection of the antibacterial activity of chitosan

    OpenAIRE

    Mayer, Gerd; Claußen, Tatjana; Heisig, Peter

    2007-01-01

    Using three bacterial strains the antibacterial activity of Chitoskin®, a chitosan-containing wound-dressing, was investigated by determining the viable bacterial cell count in liquid cultures in the absence and presence of Chitoskin®. Results were compared to those obtained for cellulose and silver-laminated cellulose.While the pure cellulose wound-dressing had no impact on the bacterial growth, Chitoskin® and, to an even greater extend, silver-laminated cellulose reduced the viable cell cou...

  4. In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Julien Sfeir

    2013-01-01

    Full Text Available Streptococcus pyogenes plays an important role in the pathogenesis of tonsillitis. The present study was conducted to evaluate the in vitro antibacterial activities of 18 essential oils chemotypes from aromatic medicinal plants against S. pyogenes. Antibacterial activity of essential oils was investigated using disc diffusion method. Minimum Inhibitory Concentration of essential oils showing an important antibacterial activity was measured using broth dilution method. Out of 18 essential oils tested, 14 showed antibacterial activity against S. pyogenes. Among them Cinnamomum verum, Cymbopogon citratus, Thymus vulgaris CT thymol, Origanum compactum, and Satureja montana essential oils exhibited significant antibacterial activity. The in vitro results reported here suggest that, for patients suffering from bacterial throat infections, if aromatherapy is used, these essential oils, considered as potential antimicrobial agents, should be preferred.

  5. Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives.

    Science.gov (United States)

    Lin, Hao; Bruhn, David F; Maddox, Marcus M; Singh, Aman P; Lee, Richard E; Sun, Dianqing

    2016-08-15

    Bacterial infections, caused by Mycobacterium tuberculosis and other problematic bacterial pathogens, continue to pose a significant threat to global public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic diarylheptanoids with diverse amine, amide, urea, and sulfonamide functionalities. Results of this study have produced macrocyclic geranylamine and 4-fluorophenethylamine substituted derivatives, exhibiting moderate to good activity against M. tuberculosis and selected Gram-positive bacterial pathogens. PMID:27406794

  6. Future prospects of antibacterial metal nanoparticles as enzyme inhibitor.

    Science.gov (United States)

    Ahmed, Khan Behlol Ayaz; Raman, Thiagarajan; Veerappan, Anbazhagan

    2016-11-01

    Nanoparticles are being widely used as antibacterial agents with metal nanoparticles emerging as the most efficient antibacterial agents. There have been many studies which have reported the mechanism of antibacterial activity of nanoparticles on bacteria. In this review we aim to emphasize on all the possible mechanisms which are involved in the antibacterial activity of nanoparticles and also to understand their mode of action and role as bacterial enzyme inhibitor by comparing their antibacterial mechanism to that of antibiotics with enzyme inhibition as a major mechanism. With the emergence of widespread antibiotic resistance, nanoparticles offer a better alternative to our conventional arsenal of antibiotics. Once the biological safety of these nanoparticles is addressed, these nanoparticles can be of great medical importance in our fight against bacterial infections. PMID:27524096

  7. The Antibacterial Applications of Graphene and Its Derivatives.

    Science.gov (United States)

    Shi, Lin; Chen, Jiongrun; Teng, Lijing; Wang, Lin; Zhu, Guanglin; Liu, Sa; Luo, Zhengtang; Shi, Xuetao; Wang, Yingjun; Ren, Li

    2016-08-01

    Graphene materials have unique structures and outstanding thermal, optical, mechanical and electronic properties. In the last decade, these materials have attracted substantial interest in the field of nanomaterials, with applications ranging from biosensors to biomedicine. Among these applications, great advances have been made in the field of antibacterial agents. Here, recent advancements in the use of graphene and its derivatives as antibacterial agents are reviewed. Graphene is used in three forms: the pristine form; mixed with other antibacterial agents, such as Ag and chitosan; or with a base material, such as poly (N-vinylcarbazole) (PVK) and poly (lactic acid) (PLA). The main mechanisms proposed to explain the antibacterial behaviors of graphene and its derivatives are the membrane stress hypothesis, the oxidative stress hypothesis, the entrapment hypothesis, the electron transfer hypothesis and the photothermal hypothesis. This review describes contributions to improving these promising materials for antibacterial applications. PMID:27389848

  8. Developing of a novel antibacterial agent by functionalization of graphene oxide with guanidine polymer with enhanced antibacterial activity

    Science.gov (United States)

    Li, Ping; Sun, Shiyu; Dong, Alideertu; Hao, Yanping; Shi, Shuangqiang; Sun, Zijia; Gao, Ge; Chen, Yuxin

    2015-11-01

    New materials with excellent antibacterial activity attract numerous research interests. Herein, a facile synthetic method of polyethylene glycol (PEG) and polyhexamethylene guanidine hydrochloride (PHGC) dual-polymer-functionalized graphene oxide (GO) (GO-PEG-PHGC), a novel antibacterial material, was reported. The as-prepared products were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), X-ray pattern (XRD) and elemental analysis. The antibacterial effect on the bacterial strain was investigated by incubating both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The results show that GO-PEG-PHGC has enhanced antibacterial activity when compared to GO, GO-PEG or GO-PHGC alone. The improved antibacterial activity was described to be related to a better dispersion of GO-PEG-PHGC in the presence of PEG. This better dispersion leads to a greater contact between the bacteria membrane and nanomaterials, therefore leading to greater cell damage. Not only Gram-negative bacteria but also Gram-positive bacteria are greatly inhibited by this antibacterial agent. With the powerful antibacterial activity as well as its low cost and facile preparation, the GO-PEG-PHGC as a novel antibacterial agent can find potential application in the areas of healthcare and environmental engineering.

  9. Investment in defense and cost of predator-induced defense along a resource gradient

    DEFF Research Database (Denmark)

    Steiner, Uli

    2007-01-01

    . In this study, I exposed tadpoles to caged predators along a resource gradient in order to estimate investment in defense and costs of defense by assessing predator-induced plasticity. Induced defenses included increased tail depth, reduced feeding, and reduced swimming activity; costs associated......An organism's investment in different traits to reduce predation is determined by the fitness benefit of the defense relative to the fitness costs associated with the allocation of time and resources to the defense. Inherent tradeoffs in time and resource allocation should result in differential...... investment in defense along a resource gradient, but competing models predict different patterns of investment. There are currently insufficient empirical data on changes in investment in defensive traits or their costs along resource gradients to differentiate between the competing allocation models...

  10. Association and host selectivity in multi-host pathogens.

    Directory of Open Access Journals (Sweden)

    José M Malpica

    Full Text Available The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.

  11. 6-Benzylaminopurine inhibits growth of Monilinia fructicola and induces defense-related mechanism in peach fruit.

    Science.gov (United States)

    Zhang, Yangyang; Zeng, Lizhen; Yang, Jiali; Zheng, Xiaodong; Yu, Ting

    2015-11-15

    This study demonstrated the inhibitory effect of 6-benzylaminopurine (BAP), the first generation synthetic cytokinin, on the invasion of Monilinia fructicola in peach fruit and the possible mechanism involved for the first time. Our results suggested that BAP treatment had a 63% lower disease incidence and approximately 10 times lower lesion diameter compared to the control throughout the incubation period. In vitro BAP showed a direct inhibitory effect on M. fructicola spore germination. BAP could prevent fruit texture deterioration and protect the cell membrane from oxidative stress, while no adverse effects were observed on fruit quality maintenance. Analysis of defense-related enzymes activities indicated that the use of BAP induced higher specific polyphenol oxidase and peroxidase activities which triggered stronger host defensive responses. Thus, our results verified the proposed mechanism of BAP in controlling M. fructicola by direct inhibitory effect, delay peach senescence and activation of defensive enzymes.

  12. A Novel Antibacterial Compound from Siegesbeckia glabrescens

    Directory of Open Access Journals (Sweden)

    Deokhoon Park

    2012-10-01

    Full Text Available The crude methanol extract of the dried aerial parts of Siegesbeckia glabrescens (Compositae showed antibacterial activity against the foodborne pathogen Staphylococcus aureus. Bioactivity-guided separation led to the isolation of 3-(dodecanoyloxy-2-(isobutyryloxy-4-methylpentanoic acid from nature for the first time. The structure was determined by spectroscopic data analysis (UV, MS, and NMR. The minimal inhibitory concentration (MIC of 3-(dodecanoyloxy-2-(isobutyryloxy-4-methylpentanoic acid against S. aureus was found to be 3.12 μg/mL. In addition, in a further antimicrobial activity assay against Gram-positive (B. subtilis, E. faecalis, P. acnes, S. epidermidis, S. schleiferi subsp. coagulans, S. agalactiae and S. pyrogens, and Gram-negative bacteria (E. coli and P. aeruginosa, and yeast strains (C. alibicans and F. neoformans, the antimicrobial activity of the compound was found to be specific for Gram-positive bacteria. The MIC values of the compound for Gram-positive bacteria ranged from 3.12 to 25 mg/mL. Furthermore, it was found that the 2-(isobutyryloxy-4-methylpentanoic acid substituent may operate as a key factor in the antibacterial activity of the compound, together with the laurate group.

  13. Silver Nanoparticles as Potential Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Gianluigi Franci

    2015-05-01

    Full Text Available Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an important activity of silver nanoparticles against bacterial biofilms. This review aims to summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly the use of nanosilver antimicrobials.

  14. Quaternary Ammonium Polyethyleneimine: Antibacterial Activity Ira

    International Nuclear Information System (INIS)

    Quaternary ammonium polyethyleneimine- (QA-PEI-) based nanoparticles were synthesized using two synthetic methods, reductive amination and N-alkylation. According to the first method, QA-PEI nanoparticles were synthesized by cross-linking with glutaraldehyde followed by reductive amination with octanal and further N-methylation with methyl iodide. The second method is based on crosslinking with dialkyl halide followed by N-alkylation with octyl halide and further N-methylation with methyl iodide. QA-PEI nanoparticles completely inhibited bacterial growth (>106 bacteria), including both Gram-positive, that is, Staphylococcus aureus at 80 μ/mL, and Gram-negative, that is, Escherichia coli at 320 μ/mL. Activity analysis revealed that the degree of alkylation and N-methylation of the QA-PEI nanoparticles plays a significant role in antibacterial activity of the reagent. The most potent compound was octyl alkylated QA-PEI alkylated at 1 : 1 mole ratio (primary amine of PEI monomer units/alkylating agent). Also, cytotoxicity studies on MAT-LyLu and MBT cell lines were performed with QA-PEI nanoparticles. These findings confirm previous reports that poly cations bearing quaternary ammonium moieties inhibit bacterial growth in vitro and have a potential use as additives in medical devices which need antibacterial properties.

  15. Photodynamic antibacterial effect of graphene quantum dots.

    Science.gov (United States)

    Ristic, Biljana Z; Milenkovic, Marina M; Dakic, Ivana R; Todorovic-Markovic, Biljana M; Milosavljevic, Momir S; Budimir, Milica D; Paunovic, Verica G; Dramicanin, Miroslav D; Markovic, Zoran M; Trajkovic, Vladimir S

    2014-05-01

    Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD. PMID:24612819

  16. Photodynamic antibacterial effect of graphene quantum dots.

    Science.gov (United States)

    Ristic, Biljana Z; Milenkovic, Marina M; Dakic, Ivana R; Todorovic-Markovic, Biljana M; Milosavljevic, Momir S; Budimir, Milica D; Paunovic, Verica G; Dramicanin, Miroslav D; Markovic, Zoran M; Trajkovic, Vladimir S

    2014-05-01

    Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.

  17. Hemipteran and dipteran pests:Effectors and plant host immune regulators

    Institute of Scientific and Technical Information of China (English)

    Isgouhi Kaloshian; Linda L Walling

    2016-01-01

    Hemipteran and dipteran insects have behavioral, cellular and chemical strategies for evading or coping with the host plant defenses making these insects particularly destructive pests worldwide. A critical component of a host plant’s defense to herbivory is innate immunity. Here we review the status of our understanding of the receptors that contribute to perception of hemipteran and dipteran pests and highlight the gaps in our knowledge in these early events in immune signaling. We also highlight recent advances in identification of the effectors that activate pattern-triggered immunity and those involved in effector-triggered immunity.

  18. Host Responses to Biofilm.

    Science.gov (United States)

    Watters, C; Fleming, D; Bishop, D; Rumbaugh, K P

    2016-01-01

    From birth to death the human host immune system interacts with bacterial cells. Biofilms are communities of microbes embedded in matrices composed of extracellular polymeric substance (EPS), and have been implicated in both the healthy microbiome and disease states. The immune system recognizes many different bacterial patterns, molecules, and antigens, but these components can be camouflaged in the biofilm mode of growth. Instead, immune cells come into contact with components of the EPS matrix, a diverse, hydrated mixture of extracellular DNA (bacterial and host), proteins, polysaccharides, and lipids. As bacterial cells transition from planktonic to biofilm-associated they produce small molecules, which can increase inflammation, induce cell death, and even cause necrosis. To survive, invading bacteria must overcome the epithelial barrier, host microbiome, complement, and a variety of leukocytes. If bacteria can evade these initial cell populations they have an increased chance at surviving and causing ongoing disease in the host. Planktonic cells are readily cleared, but biofilms reduce the effectiveness of both polymorphonuclear neutrophils and macrophages. In addition, in the presence of these cells, biofilm formation is actively enhanced, and components of host immune cells are assimilated into the EPS matrix. While pathogenic biofilms contribute to states of chronic inflammation, probiotic Lactobacillus biofilms cause a negligible immune response and, in states of inflammation, exhibit robust antiinflammatory properties. These probiotic biofilms colonize and protect the gut and vagina, and have been implicated in improved healing of damaged skin. Overall, biofilms stimulate a unique immune response that we are only beginning to understand. PMID:27571696

  19. Immediate-Early (IE) gene regulation of cytomegalovirus: IE1- and pp71-mediated viral strategies against cellular defenses.

    Science.gov (United States)

    Torres, Lilith; Tang, Qiyi

    2014-12-01

    Three crucial hurdles hinder studies on human cytomegalovirus (HCMV): strict species specificity, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of the whole genome was first accomplished, functional studies on individual genes have been the mainstream in the CMV field. Gene regulation has therefore been elucidated in a more detailed fashion. However, viral gene regulation is largely controlled by both cellular and viral components. In other words, viral gene expression is determined by the virus-host interaction. Generally, cells respond to viral infection in a defensive pattern; at the same time, viruses try to counteract the cellular defense or else hide in the host (latency). Viruses evolve effective strategies against cellular defense in order to achieve replicative success. Whether or not they are successful, cellular defenses remain in the whole viral replication cycle: entry, immediate-early (IE) gene expression, early gene expression, DNA replication, late gene expression, and viral egress. Many viral strategies against cellular defense, and which occur in the immediate-early time of viral infection, have been documented. In this review, we will summarize the documented biological functions of IE1 and pp71 proteins, especially with regard to how they counteract cellular intrinsic defenses.

  20. Immediate–Early(IE) gene regulation of cytomegalovirus:IE1-and pp71-mediated viral strategies against cellular defenses

    Institute of Scientific and Technical Information of China (English)

    Lilith; Torres; Qiyi; Tang

    2014-01-01

    Three crucial hurdles hinder studies on human cytomegalovirus(HCMV): strict species specificity, differences between in vivo and in vitro infection, and the complexity of gene regulation. Ever since the sequencing of the whole genome was first accomplished, functional studies on individual genes have been the mainstream in the CMV field. Gene regulation has therefore been elucidated in a more detailed fashion. However, viral gene regulation is largely controlled by both cellular and viral components. In other words, viral gene expression is determined by the virus–host interaction. Generally, cells respond to viral infection in a defensive pattern; at the same time, viruses try to counteract the cellular defense or else hide in the host(latency). Viruses evolve effective strategies against cellular defense in order to achieve replicative success. Whether or not they are successful, cellular defenses remain in the whole viral replication cycle: entry, immediate–early(IE) gene expression, early gene expression, DNA replication, late gene expression, and viral egress. Many viral strategies against cellular defense, and which occur in the immediate–early time of viral infection, have been documented. In this review, we will summarize the documented biological functions of IE1 and pp71 proteins, especially with regard to how they counteract cellular intrinsic defenses.