Abstract
Bacterial infections trigger robust host immune responses, while pathogens concurrently adapt to enhance survival within the host. In our previous study, we observed 24 h of Salmonella Typhi infection in Caenorhabditis elegans colonized the body of the host and also vertically transmitted to their F1 offspring generation. This study investigates host interaction-mediated modulation in S. Typhi physiology and virulence, focusing on host-derived strains from initial infection (CeP0-ST) and vertically transmitted F1 progeny (CeF1-ST), compared to the wild-type unexposed strain (WT-ST). We employed C. elegans lifespan assays, bacterial colonization, morphology, motility, gene expression, ROS estimation, and infection models using immune pathway mutants. CeP0-ST and CeF1-ST exhibited increased infectivity, faster mortality, and enhanced colonization, accompanied by reduced cell size, motility, and lipopolysaccharide (LPS)-mediated immunogenicity. This was evidenced by downregulation of fliC, ompC, ompF, and SPI-1 encoded Type III Secretion System (T3SS-1) genes (sipA, avrA, sopE). Upregulation of Vi-capsular antigen genes (tviD, tviA, viaB) suggested immune evasion, which was supported by improved host survival upon Vi-negative Ty21a strain infection. Among various C. elegans immune pathway mutants, the TGF-β pathway mutant [sma-6(-)] showed altered pathogen modulation, with reduced Vi expression and increased T3SS gene expression in derived strains. Suppressed host immune gene expression during WT-derived infections, but increased expression during sma-6 (-)-derived infections, suggests a role for TGF-β signalling in driving pathogen adaptation. These findings highlight that host interaction promotes S. Typhi immune evasion via Vi-antigen expression, potentially regulated by host TGF-β signalling, and that vertical transmission of adapted strains facilitates long-term persistence.