Salmonella relies on siderophore exploitation at low pH

Abstract Salmonella enterica, a prominent enteric pathogen, employs sophisticated iron acquisition mechanisms to overcome host-imposed iron limitation, notably through the production and uptake of siderophores—small, high-affinity iron-chelating compounds that scavenge iron from the host environment. In this study, we investigate how environmental pH influences Salmonella’s preference for its endogenous siderophores versus exogenous siderophores within the physiological range of the gastrointestinal tract. Through competition assays, gene expression analysis, and siderophore quantification, we demonstrate that Salmonella increasingly relies on exogenous siderophores under acidic conditions. This shift is attributed to reduced production of its endogenous siderophores, enterobactin and salmochelin. Deletion of the sigma factor RpoS enhances endogenous siderophore production and iron acquisition at low pH, suggesting its role in regulating iron homeostasis. Our findings reveal a pH-dependent adaptation in Salmonella’s iron acquisition strategy, highlighting the pathogen’s versatility in nutrient acquisition across varying gastrointestinal conditions. This research provides insights into Salmonella’s pathogenicity and may inform the development of targeted interventions for Salmonella infections. Competing Interest Statement The authors have declared no competing interest. Footnotes This revised version represent an improved version with some major corrections.