Identification of gene targets regulated by the IclR-like regulator SL1344_3500 in Salmonella Typhimurium

Transcriptional regulation of metabolic operons is important for optimal carbohydrate use and for mitigating the accumulation of toxic intermediates. Here, we characterize SL1344_3500, encoding a putative IclR-like regulator in Salmonella enterica Typhimurium. We present genetic and transcriptional evidence that it regulates the expression of two neighboring operons, one designated here as xynABC, enables utilization of xylonate as a sole carbon source. Furthermore, our findings indicate that SL1344_3500 is important for luminal growth in several mouse models, exerting its effects through the suppression of the xynABC operon. Based on the observation that the ΔSL1344_3500 deletion can be stably complemented in vivo, we developed a plasmid stabilization strategy. This gene complementation approach shows promise for generating stable gene reporters for long-term colonization experiments.IMPORTANCEUnderstanding transcriptional regulation in Salmonella enterica Typhimurium is crucial for revealing how enteric pathogens optimize metabolism to compete with commensals in the gut. SL1344_3500, an IclR-like transcriptional regulator controlling genes linked to sugar acid metabolism, is essential for luminal growth in mouse models through gene suppression and represents a potential target for antimicrobial development. Based on these observations, we developed stable reporter plasmids that use gene complementation of SL1344_3500 to prevent plasmid loss during long-term in vivo studies.