Global transcriptome analysis reveals Salmonella Typhimurium employs nitrate metabolism to combat bile stress

Salmonella Typhimurium is an enteric pathogen that is highly tolerant to bile. Next‐generation mRNA sequencing was performed to analyze the adaptive responses to bile in two S . Typhimurium strains: wild type (WT) and a mutant lacking cold shock protein E (Δ csp E). CspE is an RNA chaperone which is crucial for survival of S . Typhimurium during bile stress. This study identifies transcriptional responses in bile‐tolerant WT and bile‐sensitive Δ csp E. Upregulation of several genes involved in nitrate metabolism was observed, including fnr , a global regulator of nitrate metabolism. Notably, Δ fnr was susceptible to bile stress. Also, complementation with fnr lowered reactive oxygen species and enhanced the survival of bile‐sensitive Δ csp E. Importantly, intracellular nitrite amounts were highly induced in bile‐treated WT compared to Δ csp E. Also, the WT strain pre‐treated with nitrate displayed better growth with bile. These results demonstrate that nitrate‐dependent metabolism promotes adaptation of S . Typhimurium to bile.