Critical concentration of formate governs the expression of the flagellar and the pathogenicity island-1 genes inSalmonellaTyphimurium

Abstract

Salmonella enterica is a Gram-negative foodborne pathogen belonging to the family Enterobacteriaceae that accounts for global disease burden and has become a top priority pathogen. The stealthy pathogen Salmonella can sense diverse cues from the host and modify the expression of its virulence factors. Formate is one of the important constituents of Short Chain Fatty Acids (SCFAs) present in the distal ileum and has previously been studied as an important signal to promote invasion in Salmonella Typhimurium. To unravel whether endogenous formate level is also crucial for conferring virulence in Salmonella, we have created genomic knockouts of pflB (Pyruvate-formate lyase) and focA (Formate transporter), the two major contributors to formate pool in Salmonella. Perturbing the intracellular pool of formate by deletion of pflB resulted in some major reprogramming like the loss of flagella and enhanced expression of pathogenicity island-1 genes. Moreover, STM ΔpflB was associated with a higher intracellular pH and membrane damage compared to the WT strain. Our data shows that the membrane damage seen in STM ΔpflB leads to the downregulation of the flagellar apparatus mediated by the extra cytoplasmic sigma factor RpoE. Moreover, this same regulon leads to the enhanced expression of pathogenicity island-1 genes, hilA and prgH. In this study, we show for the first time that endogenous formate levels are of utmost importance to maintain the optimum pH and regulate gene expression in STM. PflB might act as a switch to maintain the optimum cytosolic pH and maximize the virulence of STM under different niches.