LuxS/AI-2 signaling in Salmonella Typhimurium regulates phoP/phoQ to protect against acidic pH for enhanced survival in macrophages
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Salmonella quorum sensing involves producing and detecting Autoinducer-2 (AI-2) signaling molecules. Our research reveals that Salmonella Typhimurium enhances AI-2 biosynthesis and transport under acidic conditions, aiding in environmental adaptation and facilitating pathogenesis in macrophages. AI-2 signaling regulates the pH-sensing two-component system genes, phoP/phoQ , ensuring cytosolic pH homeostasis, survival, and acid tolerance. It also involves regulating the Lysine/Cadaverine-mediated acid tolerance response and maintaining bacterial cytosolic pH. In this study, we show that LsrR protein, via its Y25 and R43 amino acids, apart from the lsr promoter, binds to the phoP promoter to negatively modulate the expression of phoP . This signaling ameliorates intracellular survival by modulating Salmonella Pathogenicity Island-2 (SPI-2) regulators ( ssrA/ssrB ) and SPI-2 effector expression via PhoP. Mouse models demonstrate that AI-2 signaling is essential for colonizing primary and secondary infection sites, showcasing its critical role in pathogenesis and low pH survival mechanisms in Salmonella .
