Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia

ABSTRACT Staphylococcal superantigens (SAgs) are a family of secreted toxins that stimulate T cell activation and are associated with an array of diseases in humans and livestock. Most SAgs produced by Staphylococcus aureus are encoded by mobile genetic elements, such as pathogenicity islands, bacte...

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Autores principales:	Manouk Vrieling, Stephen W. Tuffs, Gonzalo Yebra, Marleen Y. van Smoorenburg, Joana Alves, Amy C. Pickering, Joo Youn Park, Nogi Park, David E. Heinrichs, Lindert Benedictus, Timothy Connelley, Keun Seok Seo, John K. McCormick, J. Ross Fitzgerald
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Staphylococcus aureus T cells evolution pathogenesis superantigens Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1cc4076bef6448b7b578eeff51ccd2d1
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spelling	oai:doaj.org-article:1cc4076bef6448b7b578eeff51ccd2d12021-11-15T16:19:07ZPopulation Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia10.1128/mBio.02082-202150-7511https://doaj.org/article/1cc4076bef6448b7b578eeff51ccd2d12020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02082-20https://doaj.org/toc/2150-7511ABSTRACT Staphylococcal superantigens (SAgs) are a family of secreted toxins that stimulate T cell activation and are associated with an array of diseases in humans and livestock. Most SAgs produced by Staphylococcus aureus are encoded by mobile genetic elements, such as pathogenicity islands, bacteriophages, and plasmids, in a strain-dependent manner. Here, we carried out a population genomic analysis of >800 staphylococcal isolates representing the breadth of S. aureus diversity to investigate the distribution of all 26 identified SAg genes. Up to 14 SAg genes were identified per isolate with the most common gene selw (encoding a putative SAg, SElW) identified in 97% of isolates. Most isolates (62.5%) have a full-length open reading frame of selw with an alternative TTG start codon that may have precluded functional characterization of SElW to date. Here, we demonstrate that S. aureus uses the TTG start codon to translate a potent SAg SElW that induces Vβ-specific T cell proliferation, a defining feature of classical SAgs. SElW is the only SAg predicted to be expressed by isolates of the CC398 lineage, an important human and livestock epidemic clone. Deletion of selw in a representative CC398 clinical isolate, S. aureus NM001, resulted in complete loss of T cell mitogenicity in vitro, and in vivo expression of SElW by S. aureus increased the bacterial load in the liver during bloodstream infection of SAg-sensitive HLA-DR4 transgenic mice. Overall, we report the characterization of a novel, highly prevalent, and potent SAg that contributes to the pathogenesis of S. aureus infection. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen associated with an array of diseases, including life-threatening necrotizing pneumonia and infective endocarditis. The success of S. aureus as a pathogen has been linked in part to its ability to manipulate the host immune response through the secretion of toxins and immune evasion molecules. The staphylococcal superantigens (SAgs) have been studied for decades, but their role in S. aureus pathogenesis is not well understood, and an appreciation for how SAgs manipulate the host immune response to promote infection may be crucial for the development of novel intervention strategies. Here, we characterized a widely prevalent, previously cryptic, staphylococcal SAg, SElW, that contributes to the severity of S. aureus infections caused by an important epidemic clone of S. aureus CC398. Our findings add to the understanding of staphylococcal SAg diversity and function and provide new insights into the capacity of S. aureus to cause disease.Manouk VrielingStephen W. TuffsGonzalo YebraMarleen Y. van SmoorenburgJoana AlvesAmy C. PickeringJoo Youn ParkNogi ParkDavid E. HeinrichsLindert BenedictusTimothy ConnelleyKeun Seok SeoJohn K. McCormickJ. Ross FitzgeraldAmerican Society for MicrobiologyarticleStaphylococcus aureusT cellsevolutionpathogenesissuperantigensMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus T cells evolution pathogenesis superantigens Microbiology QR1-502
spellingShingle	Staphylococcus aureus T cells evolution pathogenesis superantigens Microbiology QR1-502 Manouk Vrieling Stephen W. Tuffs Gonzalo Yebra Marleen Y. van Smoorenburg Joana Alves Amy C. Pickering Joo Youn Park Nogi Park David E. Heinrichs Lindert Benedictus Timothy Connelley Keun Seok Seo John K. McCormick J. Ross Fitzgerald Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
description	ABSTRACT Staphylococcal superantigens (SAgs) are a family of secreted toxins that stimulate T cell activation and are associated with an array of diseases in humans and livestock. Most SAgs produced by Staphylococcus aureus are encoded by mobile genetic elements, such as pathogenicity islands, bacteriophages, and plasmids, in a strain-dependent manner. Here, we carried out a population genomic analysis of >800 staphylococcal isolates representing the breadth of S. aureus diversity to investigate the distribution of all 26 identified SAg genes. Up to 14 SAg genes were identified per isolate with the most common gene selw (encoding a putative SAg, SElW) identified in 97% of isolates. Most isolates (62.5%) have a full-length open reading frame of selw with an alternative TTG start codon that may have precluded functional characterization of SElW to date. Here, we demonstrate that S. aureus uses the TTG start codon to translate a potent SAg SElW that induces Vβ-specific T cell proliferation, a defining feature of classical SAgs. SElW is the only SAg predicted to be expressed by isolates of the CC398 lineage, an important human and livestock epidemic clone. Deletion of selw in a representative CC398 clinical isolate, S. aureus NM001, resulted in complete loss of T cell mitogenicity in vitro, and in vivo expression of SElW by S. aureus increased the bacterial load in the liver during bloodstream infection of SAg-sensitive HLA-DR4 transgenic mice. Overall, we report the characterization of a novel, highly prevalent, and potent SAg that contributes to the pathogenesis of S. aureus infection. IMPORTANCE Staphylococcus aureus is an important human and animal pathogen associated with an array of diseases, including life-threatening necrotizing pneumonia and infective endocarditis. The success of S. aureus as a pathogen has been linked in part to its ability to manipulate the host immune response through the secretion of toxins and immune evasion molecules. The staphylococcal superantigens (SAgs) have been studied for decades, but their role in S. aureus pathogenesis is not well understood, and an appreciation for how SAgs manipulate the host immune response to promote infection may be crucial for the development of novel intervention strategies. Here, we characterized a widely prevalent, previously cryptic, staphylococcal SAg, SElW, that contributes to the severity of S. aureus infections caused by an important epidemic clone of S. aureus CC398. Our findings add to the understanding of staphylococcal SAg diversity and function and provide new insights into the capacity of S. aureus to cause disease.
format	article
author	Manouk Vrieling Stephen W. Tuffs Gonzalo Yebra Marleen Y. van Smoorenburg Joana Alves Amy C. Pickering Joo Youn Park Nogi Park David E. Heinrichs Lindert Benedictus Timothy Connelley Keun Seok Seo John K. McCormick J. Ross Fitzgerald
author_facet	Manouk Vrieling Stephen W. Tuffs Gonzalo Yebra Marleen Y. van Smoorenburg Joana Alves Amy C. Pickering Joo Youn Park Nogi Park David E. Heinrichs Lindert Benedictus Timothy Connelley Keun Seok Seo John K. McCormick J. Ross Fitzgerald
author_sort	Manouk Vrieling
title	Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
title_short	Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
title_full	Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
title_fullStr	Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
title_full_unstemmed	Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia
title_sort	population analysis of <named-content content-type="genus-species">staphylococcus aureus</named-content> reveals a cryptic, highly prevalent superantigen selw that contributes to the pathogenesis of bacteremia
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/1cc4076bef6448b7b578eeff51ccd2d1
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Population Analysis of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia

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