A novel contribution ofspvBto pathogenesis ofSalmonellaTyphimurium by inhibiting autophagy in host cells

Abstract

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.

Salmonella Interacts With Autophagy to Offense or Defense

“…Of these, spvB is a structural gene, which has a great influence on bacterial virulence (Guiney and Fierer, 2011). It has been found that spvB can depolymerize actin, inhibit autophagy in human epithelial HeLa cells, macrophage-like J774A.1 cells, and BALB/c mice, and aggravate the host's inflammatory damage to Salmonella infection (Chu et al, 2016). Moreover, in the zebrafish model infected with Salmonella, it was also confirmed that Salmonella spvB could promote bacterial survival and intestinal damage by inhibiting autophagy (Li et al, 2016;Wu et al, 2016).…”

Salmonella spvC Gene Inhibits Pyroptosis and Intestinal Inflammation to Aggravate Systemic Infection in Mice

“…Most pathogenic Salmonella harbor a pSLT virulence plasmid of around 90 kb that contains a highly conserved 8-kb region of five genes (spvRABCD), which have been reported to be implicated in intracellular survival and growth (Guiney and Fierer, 2011;Passaris et al, 2018). Previously, we showed that Salmonella spvB gene could reduce host cell autophagy and regulate intracellular iron homeostasis (Chu et al, 2016;Yang et al, 2019). spvC is another essential factor of Salmonella virulence determinant, and its encoding product, SpvC, shares 63% identity at the amino acid level with OspF of Shigella flexneri and exhibits the same phosphothreonine lyase activity on host mitogen-activated protein kinase (MAPK).…”

Detection of virulence and specific genes of Salmonella sp. indigenous from Jember, Indonesia

“…Salmonella Enterica Serovar Typhimurium strain, found on the rat, was inoculated subcutaneously, and contained spvB gene (Matsui et al 2001). spvB gene expressed ADPribosylation enzyme which inhibited the process of polymerization actin in host cell, so it could inhibit the fusion between phagocyte and lysosome (Chu et al 2016). spvD gene reduced the pro-inflammation regulation by inhibiting promotor activation which was controlled by NF-kB (Silva et al 2017;Liu et al 2017).…”