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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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.
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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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