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

Abstract

<i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>). Typhimurium is a primary foodborne pathogen infecting both humans and animals. <i>Salmonella</i> plasmid virulence C (<i>spvC</i>) gene is closely related to <i>S</i>. Typhimurium dissemination in mice, while the mechanisms remain to be fully elucidated. Pyroptosis, a gasdermin-mediated inflammatory cell death, plays a role in host defense against bacterial infection, whereas the effect of <i>spvC</i> on pyroptosis and its function in inflammatory injury induced by <i>S</i>. Typhimurium are rather limited. In our study, C57BL/6 mice and J774A.1 cells infected with <i>S</i>. Typhimurium wild-type strain SL1344, <i>spvC</i> deletion mutant, <i>spvC</i> K136A site-directed mutant, and complemented strain were used to investigate potential pathogenesis of <i>spvC</i>. We verity that SpvC attenuates intestinal inflammation, suppresses pyroptosis through phosphothreonine lyase activity, and reduces pyroptosis in the ceca. Moreover, the reduction of inflammation via <i>spvC</i> results in systemic infection. These findings demonstrate that <i>spvC</i> inhibits pyroptosis and intestinal inflammation to promote bacterial dissemination, which provide new strategies for controlling systemic infection caused by <i>Salmonella</i> and novel insights for the treatment of other corresponding diseases.