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Infection and immunity 24건

  1. [해외논문]   Characterization of the Pathogenicity of Streptococcus intermedius TYG1620 Isolated from a Human Brain Abscess Based on the Complete Genome Sequence with Transcriptome Analysis and Transposon Mutagenesis in a Murine Subcutaneous Abscess Model   SCI SCIE

    Hasegawa, Noriko (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Sekizuka, Tsuyoshi (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Sugi, Yutaka (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Kawakami, Nobuhiro (Department of Pediatrics, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan ) , Ogasawara, Yumiko (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Kato, Kengo (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Yamashita, Akifumi (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Takeuchi, Fumihiko (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan ) , Kuroda, Makoto (Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious D)
    Infection and immunity v.85 no.2 ,pp. e00886-16 - e00886-16 , 2017 , 0019-9567 ,

    초록

    Streptococcus intermedius is known to cause periodontitis and pyogenic infections in the brain and liver. Here we report the complete genome sequence of strain TYG1620 (genome size, 2,006,877 bp; GC content, 37.6%; 2,020 predicted open reading frames [ORFs]) isolated from a brain abscess in an infant. Comparative analysis of S. intermedius genome sequences suggested that TYG1620 carries a notable type VII secretion system (T7SS), two long repeat regions, and 19 ORFs for cell wall-anchored proteins (CWAPs). To elucidate the genes responsible for the pathogenicity of TYG1620, transcriptome analysis was performed in a murine subcutaneous abscess model. The results suggest that the levels of expression of small hypothetical proteins similar to phenol-soluble modulin β1 (PSMβ1), a staphylococcal virulence factor, significantly increased in the abscess model. In addition, an experiment in a murine subcutaneous abscess model with random transposon (Tn) mutant attenuation suggested that Tn mutants with mutations in 212 ORFs in the Tn mutant library were attenuated in the murine abscess model (629 ORFs were disrupted in total); the 212 ORFs are putatively essential for abscess formation. Transcriptome analysis identified 37 ORFs, including paralogs of the T7SS and a putative glucan-binding CWAP in long repeat regions, to be upregulated and attenuated in vivo . This study provides a comprehensive characterization of S. intermedius pathogenicity based on the complete genome sequence and a murine subcutaneous abscess model with transcriptome and Tn mutagenesis, leading to the identification of pivotal targets for vaccines or antimicrobial agents for the control of S. intermedius infections.

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  2. [해외논문]   Reply to “On the Impact Factor and the ASM Editorial Policy”   SCI SCIE

    Fang, Ferric C. (Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle, Washington, USA ) , Casadevall, Arturo (Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA)
    Infection and immunity v.85 no.2 ,pp. e00989-16 - e00989-16 , 2017 , 0019-9567 ,

    초록

    Streptococcus intermedius is known to cause periodontitis and pyogenic infections in the brain and liver. Here we report the complete genome sequence of strain TYG1620 (genome size, 2,006,877 bp; GC content, 37.6%; 2,020 predicted open reading frames [ORFs]) isolated from a brain abscess in an infant. Comparative analysis of S. intermedius genome sequences suggested that TYG1620 carries a notable type VII secretion system (T7SS), two long repeat regions, and 19 ORFs for cell wall-anchored proteins (CWAPs). To elucidate the genes responsible for the pathogenicity of TYG1620, transcriptome analysis was performed in a murine subcutaneous abscess model. The results suggest that the levels of expression of small hypothetical proteins similar to phenol-soluble modulin β1 (PSMβ1), a staphylococcal virulence factor, significantly increased in the abscess model. In addition, an experiment in a murine subcutaneous abscess model with random transposon (Tn) mutant attenuation suggested that Tn mutants with mutations in 212 ORFs in the Tn mutant library were attenuated in the murine abscess model (629 ORFs were disrupted in total); the 212 ORFs are putatively essential for abscess formation. Transcriptome analysis identified 37 ORFs, including paralogs of the T7SS and a putative glucan-binding CWAP in long repeat regions, to be upregulated and attenuated in vivo . This study provides a comprehensive characterization of S. intermedius pathogenicity based on the complete genome sequence and a murine subcutaneous abscess model with transcriptome and Tn mutagenesis, leading to the identification of pivotal targets for vaccines or antimicrobial agents for the control of S. intermedius infections.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  3. [해외논문]   The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines   SCI SCIE

    Espinosa, Diego A. (Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA ) , Vega-Rodriguez, Joel (Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA ) , Flores-Garcia, Yevel (Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA ) , Noe, Amy R. (Leidos Life Sciences, Frederick, Maryland, USA ) , Muñ (Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA ) , oz, Christian (Pfenex Inc., San Diego, California, USA ) , Coleman, Russell (Pfenex Inc., San Diego, California, USA ) , Bruck, Torben (Pfenex Inc., San Diego, California, USA ) , Haney, Keith (Pfenex Inc., San Diego, California, USA ) , Stevens, Alex (Pfenex Inc., San Diego, California, USA ) , Retallack, Diane (Pfenex Inc., San Diego, California, USA ) , Allen, Jeff (Infectious Disease Research Institute, Seattle, Washington, USA ) , Vedvick, Thomas S. (Infec) , Fox, Christopher B. , Reed, Steven G. , Howard, Randall F. , Salman, Ahmed M. , Janse, Chris J. , Khan, Shahid M. , Zavala, Fidel , Gutierrez, Gabriel M.
    Infection and immunity v.85 no.2 ,pp. e00498-16 - e00498-16 , 2017 , 0019-9567 ,

    초록

    Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo . Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission.

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  4. [해외논문]   NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice   SCI SCIE

    Bast, Antje (Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany ) , Kubis, Helen (Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany ) , Holtfreter, Birte (Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany ) , Ribback, Silvia (Institute of Pathology, University Medicine Greifswald, Greifswald, Germany ) , Martin, Heiner (Institute for Biomedical Engineering, University of Rostock, Rostock, Germany ) , Schreiner, Helen C. (Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry, Newark, New Jersey, USA ) , Dominik, Malte J. (Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany ) , Breitbach, Katrin (Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany ) , Dombrowski, Frank (Institute of Pathology, University Medicine Greifswald, Greifswald, Germany ) , Kocher, Thomas (Unit of Periodontology) , Steinmetz, Ivo
    Infection and immunity v.85 no.2 ,pp. e00849-16 - e00849-16 , 2017 , 0019-9567 ,

    초록

    Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans -induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   On the Impact Factor and the ASM Editorial Policy   SCI SCIE

    Arguelles, Juan Carlos (Área de MicrobiologÁía, Facultad de BiologÁíía, Universidad de Murcia, Murcia, and IMIB—Arrixaca, Murcia, Spain)
    Infection and immunity v.85 no.2 ,pp. e00933-16 - e00933-16 , 2017 , 0019-9567 ,

    초록

    Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans -induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus   SCI SCIE

    Chan, Liana C. (Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California, USA ) , Chaili, Siyang (Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA ) , Filler, Scott G. (Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA ) , Miller, Lloyd S. (Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA ) , Solis, Norma V. (Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA ) , Wang, Huiyuan (Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California, USA ) , Johnson, Colin W. (Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California, USA ) , Lee, Hong K. (Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA ) , Diaz, Luis F. (Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, USA ) , Yeaman, Michael R. (Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California, USA)
    Infection and immunity v.85 no.2 ,pp. e00876-16 - e00876-16 , 2017 , 0019-9567 ,

    초록

    Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due to S. aureus , including methicillin-resistant S. aureus (MRSA) strains, despite high titers of specific antibodies and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to the protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type and rag1 −/− mice in the BALB/c and C57BL/6 backgrounds. Prior infection (priming) of wild-type and rag1 −/− mice of either background afforded protection against repeat infection, as evidenced by reduced abscess severities and decreased CFU densities compared to those in naive controls. Interestingly, protection was greater on the previously infected flank than on the naive flank for wild-type and rag1 −/− mice. For wild-type mice, protective efficacy corresponded to increased infiltration of neutrophils (polymorphonuclear leukocytes [PMN]), macrophages (MΦ), Langerin + dendritic cells (LDC), and natural killer (NK) cells. Protection was associated with the induction of interleukin-17A (IL-17A), IL-22, and gamma interferon (IFN-γ) as well as the antimicrobial peptides CRAMP and mβD-3. Priming also protected rag1 −/− mice against recurring SSSI, with increased MΦ and LDC infiltration and induction of IL-22, CRAMP, and mβD-3. These findings suggest that innate immune memory, mediated by specific cellular and molecular programs, likely contributes to the localized host defense in recurrent MRSA SSSI. These insights support the development of targeted immunotherapeutic strategies to address the challenge of MRSA infection.

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  7. [해외논문]   Inhibition of Antigen-Specific and Nonspecific Stimulation of Bovine T and B Cells by Lymphostatin from Attaching and Effacing Escherichia coli   SCI SCIE

    Cassady-Cain, Robin L. (The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom ) , Blackburn, Elizabeth A. (The Centre for Translational and Chemical Biology, University of Edinburgh, Edinburgh, United Kingdom ) , Bell, Charlotte R. (The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom ) , Elshina, Elizaveta (The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom ) , Hope, Jayne C. (The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom ) , Stevens, Mark P. (The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom)
    Infection and immunity v.85 no.2 ,pp. e00845-16 - e00845-16 , 2017 , 0019-9567 ,

    초록

    Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally encoded 365-kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonization of cattle by EHEC serogroup O5, O111, and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill defined. Using purified recombinant protein, we demonstrated that lymphostatin inhibits mitogen-activated proliferation of bovine T cells and, to a lesser extent, proliferation of cytokine-stimulated B cells, but not NK cells. It broadly affected the T cell compartment, inhibiting all cell subsets (CD4, CD8, WC-1, and γδ T cell receptor [γδ-TCR]) and cytokines examined (interleukin 2 [IL-2], IL-4, IL-10, IL-17A, and gamma interferon [IFN-γ]) and rendered T cells refractory to mitogen for a least 18 h after transient exposure. Lymphostatin was also able to inhibit proliferation of T cells stimulated by IL-2 and by antigen presentation using a Theileria -transformed cell line and autologous T cells from Theileria -infected cattle. We conclude that lymphostatin is likely to act early in T cell activation, as stimulation of T cells with concanavalin A, but not phorbol 12-myristate 13-acetate combined with ionomycin, was inhibited. Finally, a homologue of lymphostatin from E. coli O157:H7 (ToxB; L7095) was also found to possess comparable inhibitory activity against T cells, indicating a potentially conserved strategy for interference in adaptive responses by attaching and effacing E. coli .

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  8. [해외논문]   The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen Species Resistance via Transcriptional Regulation of Staphyloxanthin Production   SCI SCIE

    Hall, Jeffrey W. (Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA ) , Yang, Junshu (Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA ) , Guo, Haiyong (Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA ) , Ji, Yinduo (Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA)
    Infection and immunity v.85 no.2 ,pp. e00838-16 - e00838-16 , 2017 , 0019-9567 ,

    초록

    Staphylococcus aureus is an important opportunistic pathogen and is the etiological agent of many hospital- and community-acquired infections. The golden pigment, staphyloxanthin, of S. aureus colonies distinguishes it from other staphylococci and related Gram-positive cocci. Staphyloxanthin is the product of a series of biosynthetic steps that produce a unique membrane-embedded C 30 golden carotenoid and is an important antioxidant. We observed that a strain with an inducible airR overexpression cassette had noticeably increased staphyloxanthin production compared to the wild-type strain under aerobic culturing conditions. Further analysis revealed that depletion or overproduction of the AirR response regulator resulted in a corresponding decrease or increase in staphyloxanthin production and susceptibility to killing by hydrogen peroxide, respectively. Furthermore, the genetic elimination of staphyloxanthin during AirR overproduction abolished the protective phenotype of increased staphyloxanthin production in a whole-blood survival assay. Promoter reporter and gel shift assays determined that the AirR response regulator is a direct positive regulator of the staphyloxanthin-biosynthetic operon, crtOPQMN , but is epistatic to alternative sigma factor B. Taken together, these data indicate that AirSR positively regulates the staphyloxanthin-biosynthetic operon crtOPQMN , promoting survival of S. aureus in the presence of oxidants.

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  9. [해외논문]   Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22   SCI SCIE

    Porte, Ré (Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL–Center for Infection and Immunity of Lille, Lille, France ) , mi (Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL–Center for Infection and Immunity of Lille, Lille, France ) , Van Maele, Laurye (Laboratory for Vaccine Research, Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay ) , Mué (Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL–Center for Infection and Immunity of Lille, Lille, France ) , ñ (Ludwig Institute for Cancer Research, Brussels Branch, and de Duve Institute, Universitéñééé) , oz-Wolf, Natalia (Catholique de Louvain, Brussels, Belgium ) , Foligné (Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL–Center for Infection and Immunity of Lille, Lille, France ) , ñ (Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille,) , é , , Benoit , Dumoutier, Laure , Tabareau, Julien , Cayet, Delphine , Gosset, Pierre , Jonckheere, Nicolas , Van Seuningen, Isabelle , Chabalgoity, José , ñ , é , é , A. , Simonet, Michel , Lamkanfi, Mohamed , Renauld, Jean-Christophe , Sirard, Jean-Claude , Carnoy, Christophe
    Infection and immunity v.85 no.2 ,pp. e00806-16 - e00806-16 , 2017 , 0019-9567 ,

    초록

    Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine). We found that systemic administration of flagellin significantly increased the survival rate after intestinal infection (but not systemic infection) by Y. pseudotuberculosis . This protection was associated with a low bacterial count in the gut and the spleen. In contrast, no protection was afforded by administration of the TLR4 agonist lipopolysaccharide, suggesting the presence of a flagellin-specific effect. Lastly, we found that TLR5- and MyD88-mediated signaling was required for the protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was involved.

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  10. [해외논문]   Phagosomal Neutralization by the Fungal Pathogen Candida albicans Induces Macrophage Pyroptosis   SCI SCIE

    Vylkova, Slavena , Lorenz, Michael C.
    Infection and immunity v.85 no.2 ,pp. e00832-16 - e00832-16 , 2017 , 0019-9567 ,

    초록

    The interaction of Candida albicans with the innate immune system is the key determinant of the pathogen/commensal balance and has selected for adaptations that facilitate the utilization of nutrients commonly found within the host, including proteins and amino acids; many of the catabolic pathways needed to assimilate these compounds are required for persistence in the host. We have shown that C. albicans co-opts amino acid catabolism to generate and excrete ammonia, which raises the extracellular pH, both in vitro and in vivo and induces hyphal morphogenesis. Mutants defective in the uptake or utilization of amino acids, such as those lacking STP2 , a transcription factor that regulates the expression of amino acid permeases, are impaired in multiple aspects of fungus-macrophage interactions resulting from an inability to neutralize the phagosome. Here we identified a novel role in amino acid utilization for Ahr1p, a transcription factor previously implicated in regulation of adherence and hyphal morphogenesis. Mutants lacking AHR1 were defective in growth, alkalinization, and ammonia release on amino acid-rich media, similar to stp2 Δ and ahr1 Δ stp2 Δ cells, and occupied more acidic phagosomes. Notably, ahr1 Δ and stp2 Δ strains did not induce pyroptosis, as measured by caspase-1-dependent interleukin-1β release, though this phenotype could be suppressed by pharmacological neutralization of the phagosome. Altogether, we show that C. albicans -driven neutralization of the phagosome promotes hyphal morphogenesis, sufficient for induction of caspase-1-mediated macrophage lysis.

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