Repurposing Host Defense and Microbial Metabolism for Salmonella Gut Colonization

Salmonella enterica serovar Typhimurium (STm) is a leading cause of diarrheal disease and efficiently colonizes the gut lumen despite microbiota-mediated colonization resistance. Emerging evidence indicates that STm does not simply evade or overcome these barriers, but instead exploits host immune responses and microbiota-derived metabolic activities to create a permissive intestinal niche. In this review, we discuss recent advances in our understanding of STm gut colonization, with a focus on how host antimicrobial factors and microbiota-derived metabolites are repurposed to promote pathogen growth, motility, and invasion. We highlight findings showing that the antimicrobial lectin RegIIIβ, together with microbiota-dependent metabolites such as fatty acid-derived cues and polyamines, can unexpectedly facilitate STm colonization. Together, these studies support a model in which host defense programs and microbial metabolism are redirected to promote pathogen fitness, revealing potential therapeutic opportunities for controlling enteric infections.