Fatty Acid Homeostasis Tunes Flagellar Motility by Activating Phase 2 Flagellin Expression, Contributing to Salmonella Gut Colonization.

Long-chain-fatty-acid (LCFA) metabolism is a fundamental cellular process in bacteria that is involved in lipid homeostasis, energy production, and infection. However, the role of LCFA metabolism in Salmonella enterica serovar Typhimurium ( S . Tm) gut infection remains unclear. Here, using a murine gastroenteritis infection model, we demonstrate involvement of LCFA metabolism in S . Tm gut colonization. The LCFA metabolism-associated transcriptional regulator FadR contributes to S . Tm gut colonization. fadR deletion alters the gene expression profile and leads to aberrant flagellar motility of S . Tm. Colonization defects in the fadR mutant are attributable to altered swimming behavior characterized by less frequently smooth swimming, resulting from reduced expression of the phase 2 flagellin FljB. Notably, changes in lipid LCFA composition by fadR deletion lead to reduced expression of fljB , which is restored by exogenous LCFA. Therefore, LCFA homeostasis may maintain proper flagellar motility by activating fljB expression, contributing to S . Tm gut colonization. Our findings improve the understanding of the effect of luminal LCFA on the virulence of enteric pathogens.