The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection
Watkins, Robert L.
Pallister, Kyler B.
Voyich, Jovanka M.
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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-γproduction 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.
Watkins, Robert L., Kyler B. Pallister, and Jovanka M. Voyich. “The SaeR/S Gene Regulatory System Induces a Pro-Inflammatory Cytokine Response During Staphylococcus Aureus Infection.” Edited by Binh An Diep. PLoS ONE 6, no. 5 (May 13, 2011): e19939. doi:10.1371/journal.pone.0019939.
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