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Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen succes...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140855/ https://www.ncbi.nlm.nih.gov/pubmed/25144687 http://dx.doi.org/10.1371/journal.ppat.1004298 |
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author | Cheung, Gordon Y. C. Kretschmer, Dorothee Duong, Anthony C. Yeh, Anthony J. Ho, Trung V. Chen, Yan Joo, Hwang-Soo Kreiswirth, Barry N. Peschel, Andreas Otto, Michael |
author_facet | Cheung, Gordon Y. C. Kretschmer, Dorothee Duong, Anthony C. Yeh, Anthony J. Ho, Trung V. Chen, Yan Joo, Hwang-Soo Kreiswirth, Barry N. Peschel, Andreas Otto, Michael |
author_sort | Cheung, Gordon Y. C. |
collection | PubMed |
description | Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms. |
format | Online Article Text |
id | pubmed-4140855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41408552014-08-25 Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection Cheung, Gordon Y. C. Kretschmer, Dorothee Duong, Anthony C. Yeh, Anthony J. Ho, Trung V. Chen, Yan Joo, Hwang-Soo Kreiswirth, Barry N. Peschel, Andreas Otto, Michael PLoS Pathog Research Article Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms. Public Library of Science 2014-08-21 /pmc/articles/PMC4140855/ /pubmed/25144687 http://dx.doi.org/10.1371/journal.ppat.1004298 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Cheung, Gordon Y. C. Kretschmer, Dorothee Duong, Anthony C. Yeh, Anthony J. Ho, Trung V. Chen, Yan Joo, Hwang-Soo Kreiswirth, Barry N. Peschel, Andreas Otto, Michael Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title | Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title_full | Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title_fullStr | Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title_full_unstemmed | Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title_short | Production of an Attenuated Phenol-Soluble Modulin Variant Unique to the MRSA Clonal Complex 30 Increases Severity of Bloodstream Infection |
title_sort | production of an attenuated phenol-soluble modulin variant unique to the mrsa clonal complex 30 increases severity of bloodstream infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140855/ https://www.ncbi.nlm.nih.gov/pubmed/25144687 http://dx.doi.org/10.1371/journal.ppat.1004298 |
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