GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337684/primary200OKTranscriptomicsSalmonella enterica subsp. enterica serovar TyphiExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337684GEOGSEfalseOmpW-mediated sensing of MUC2 GalNAc contributes to the ileal tropism of Salmonella Typhi [STy]Salmonella Typhi (STy), the causative agent of typhoid fever, preferentially infects the ileum, but the basis for this preference has remained unknown. We show that STy exploits MUC2-derived monosaccharides, such as GalNAc, to upregulate invasion and target the ileum—opposite to the response of closely related S. Typhimurium (STm), whose invasion is inhibited by MUC2. Three STy-specific extracellular residues of the outer-membrane protein OmpW (K141/T142/Q193) engage GalNAc, and a periplasmic relay through the short FepE_STy, RS12510, and TonB transmits this signal to activate the master invasion regulator HilD. Mice lacking MUC2 or gut microbiota lose STy ileal tropism, which is restored by oral GalNAc-containing monosaccharides. An OmpW triple-mutant STy strain establishes a murine oral STy infection model, identifying STy–MUC2 glycan interactions as one of the earliest steps of typhoid pathogenesis and a potential target for prevention.2026/07/15GSE337684GSM9859478GSM9859479GSM9859481GSM9859480GSM9859483GSM985948235790337684Salmonella enterica subsp. enterica serovar Typhi