Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease

ABSTRACT Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more...

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Autores principales:	Amy Jenkins, Binh An Diep, Thuy T. Mai, Nhung H. Vo, Paul Warrener, Joann Suzich, C. Kendall Stover, Bret R. Sellman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/99ca599d3f3e41d98e7f907ec5f15078
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spelling	oai:doaj.org-article:99ca599d3f3e41d98e7f907ec5f150782021-11-15T15:41:18ZDifferential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease10.1128/mBio.02272-142150-7511https://doaj.org/article/99ca599d3f3e41d98e7f907ec5f150782015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02272-14https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. IMPORTANCE Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.Amy JenkinsBinh An DiepThuy T. MaiNhung H. VoPaul WarrenerJoann SuzichC. Kendall StoverBret R. SellmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Amy Jenkins Binh An Diep Thuy T. Mai Nhung H. Vo Paul Warrener Joann Suzich C. Kendall Stover Bret R. Sellman Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
description	ABSTRACT Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. IMPORTANCE Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.
format	article
author	Amy Jenkins Binh An Diep Thuy T. Mai Nhung H. Vo Paul Warrener Joann Suzich C. Kendall Stover Bret R. Sellman
author_facet	Amy Jenkins Binh An Diep Thuy T. Mai Nhung H. Vo Paul Warrener Joann Suzich C. Kendall Stover Bret R. Sellman
author_sort	Amy Jenkins
title	Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
title_short	Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
title_full	Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
title_fullStr	Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
title_full_unstemmed	Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease
title_sort	differential expression and roles of <named-content content-type="genus-species">staphylococcus aureus</named-content> virulence determinants during colonization and disease
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/99ca599d3f3e41d98e7f907ec5f15078
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Differential Expression and Roles of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Virulence Determinants during Colonization and Disease

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