A novel contribution of spvB to pathogenesis of Salmonella Typhimurium by inhibiting autophagy in host cells
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Yuanyuan Chu1, Song Gao1, Ting Wang1, Jing Yan1, Guangmei Xu1, Yuanyuan Li1, Hua Niu1, Rui Huang1, Shuyan Wu1
1Department of Microbiology, Medical College of Soochow University, Suzhou, P. R. China
Rui Huang, e-mail: [email protected]
Shuyan Wu, e-mail: [email protected]
Keywords: Salmonella, spvB, autophagy, autophagic flux
Received: July 03, 2015 Accepted: January 13, 2016 Published: January 22, 2016
Salmonella plasmid virulence genes (spv) are highly conserved in strains of clinically important Salmonella serovars. It is essential for Salmonella plasmid-correlated virulence, although the exact mechanism remains to be elucidated. Autophagy has been reported to play an important role in host immune responses limiting Salmonella infection. Our previous studies demonstrated that Salmonella conjugative plasmid harboring spv genes could enhance bacterial cytotoxicity by inhibiting autophagy. In the present study, we investigated whether spvB, which is one of the most important constituents of spv ORF could intervene in autophagy pathway. Murine macrophage-like cells J774A.1, human epithelial HeLa cells, and BALB/c mice infected with Salmonella Typhimurium wild type, mutant and complementary strains (carrying or free spvB or complemented only with ADP-ribosyltransferase activity of SpvB) were used in vitro and in vivo assay, respectively. To further explore the molecular mechanisms, both SpvB ectopic eukaryotic expression system and cells deficient in essential autophagy components by siRNA were generated. Results indicated that spvB could suppress autophagosome formation through its function in depolymerizing actin, and aggravate inflammatory injury of the host in response to S. Typhimurium infection. Our studies demonstrated virulence of spvB involving in inhibition of autophagic flux for the first time, which could provide novel insights into Salmonella pathogenesis, and have potential application to develop new antibacterial strategies for Salmonellosis.
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