Lei L, Wang W, Xia C, Liu F

Effector proteins encoded by Salmonella pathogenicity islands play a key role in promoting bacterial intracellular survival, colonization, and pathogenesis. In this study, we investigated the function of the virulence-associated effector SrfA (SsrAB regulated factor) both in macrophages in vitro and in infected mice in vivo. SrfA was secreted into the ...

Read More

cytoplasm during S. Typhimurium infection and disassociated IL-1R-associated kinase-1 (IRAK-1) from the IRAK-1-Toll interacting protein (Tollip) complex by interacting with Tollip. The released IRAK-1 was phosphorylated and subsequently activated the NF-κB signaling pathway, which enhanced the LPS-induced expression of inflammatory cytokines, such as IL-8, IL-1β, and TNF-α. The coupling of ubiquitin to endoplasmic reticulum degradation aa 183-219 domain of Tollip is the binding region for SrfA, and both the MDaa207-226 and CTaa357-377 regions of SrfA mediate binding to Tollip and NF-κB signaling activation. Deletion of SrfA in S. Typhimurium had no notable effects on its replication but impaired the induction of NF-κB activation in infected macrophages. The mice infected with srfA-deficient bacteria exhibited a decreased inflammatory response and an increased survival rate compared with those infected with wild-type S. Typhimurium. We conclude that SrfA is a novel Salmonella virulence effector that helps modulate host inflammatory responses by promoting NF-κB signaling activation.

Date: Jan. 15, 2016

View in: Pubmed Google Scholar

191880