Relationship between virulence regulation and trans-membrane efflux in Salmonella

SlyA is a member of the MarR family of transcription factors, which are subject to allosteric inhibition by small molecule ligands. However, despite their broad distribution and conservation, no endogenous ligands have been identified for SlyA or related MFTFs. SlyA is essential for virulence in the enteric pathogen Salmonella Typhimurium, where it functions as a counter-silencer, upregulating the gene expression of many genes required for virulence. We hypothesized that if SlyA is sensitive to an endogenous ligand, that ligand might be subject to trans-membrane efflux, and accumulate in cells where efflux has been disrupted. TolC is the essential outer membrane exporter of many efflux pumps, we theorized that mutation of tolC should result in the accumulation of any endogenous ligands, and the subsequent inhibition of SlyA. To test this, we generated slyA and tolC mutants in S. Typhimurium 14028s and performed RNA-Seq on cultures grown in virulence-inducing conditions.