This review examines how Salmonella survives hostile conditions within the mammalian and avian gastrointestinal tract to cause foodborne disease. The bacterium encounters multiple stress conditions after food ingestion, including extreme stomach acidity (pH as low as 1.5), elevated bile salts, osmolytes, and commensal bacterial metabolites in the intestines, plus low oxygen tension. To survive stomach acidity, Salmonella induces an acid tolerance response involving pH homeostatic systems (lysine and arginine decarboxylase pathways), synthesis of acid shock proteins (controlled by regulators like RpoS, Fur, PhoP/PhoQ, and OmpR), and modifications to membrane fatty acid composition, particularly conversion of unsaturated to cyclopropane fatty acids. In the intestine, Salmonella exhibits inherent bile tolerance through multiple genetic mechanisms involving efflux pumps (AcrAB), lipopolysaccharide modifications, DNA repair systems, and two-component regulatory systems. Many bile-tolerance genes also reduce virulence when disrupted, suggesting overlap between survival and pathogenic mechanisms. Bile acts as a signaling molecule that Salmonella responds to by modulating gene expression to promote survival while suppressing invasion genes, indicating sophisticated environmental sensing during infection.

Key findings

• Salmonella survives stomach acid through acid tolerance response mechanisms including lysine/arginine decarboxylase systems, acid shock proteins, and changes in membrane fatty acid composition that reduce fluidity and oxidative damage.
• The RpoS sigma factor controls at least 10 acid shock proteins and is essential for acid survival and virulence, with RpoS-deficient mutants showing increased acid sensitivity and attenuated pathogenesis.
• Over 160 genes contribute to Salmonella bile tolerance including efflux pumps, DNA repair systems, and lipopolysaccharide biosynthesis genes, with many of these genes also required for gastrointestinal virulence.
• Bile salts induce DNA damage and oxidative stress in Salmonella, triggering SOS response and requiring functional DNA repair and antioxidant defense systems for survival.
• Bile acts as a signal molecule that represses Salmonella invasion genes, allowing the bacterium to resist epithelial invasion while transiting the intestine, suggesting strategic gene regulation during infection.