Watkins, Robert L.Pallister, Kyler B.Voyich, Jovanka M.2019-04-222019-04-222011-05Watkins, 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.0019939.1932-6203https://scholarworks.montana.edu/handle/1/15453Community-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.enCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.https://creativecommons.org/licenses/by/4.0/legalcodeArticle