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PLoS One. 2011;6(5):e19939. doi: 10.1371/journal.pone.0019939. Epub 2011 May 13.

The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

Author information

1
Department of Immunology/Infectious Diseases, Montana State University-Bozeman, Bozeman, Montana, United States of America.

Abstract

Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

PMID:
21603642
PMCID:
PMC3094403
DOI:
10.1371/journal.pone.0019939
[Indexed for MEDLINE]
Free PMC Article

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