Temporal Regulation of a Typhimurium Virulence Factor by the Transcriptional Regulator YdcR.

We previously examined proteome within infected host cells and found differential expression of many proteins with defined functional roles such as metabolism or virulence. However, the precise roles of other altered proteins in pathogenesis are largely unknown. A putative transcriptional regulator, YdcR, was highly induced intracellularly whereas barely expressed , implicating potential relevance to bacterial infection. To unveil its physiological functions, we exploited quantitative proteomics of intracellular and found that genetic ablation of resulted in severe repression of SrfN, a known virulence factor. Immunoblotting, qRT-PCR, and β-galactosidase assays further demonstrate YdcR-dependent transcription and expression of Moreover, we found physical interaction of YdcR with the promoter region of , suggesting direct activation of its transcription. Importantly, a mutant lacking was markedly attenuated in a mouse model of infection. Our findings reveal that YdcR temporally regulates the virulence factor SrfN during infection, thus contributing to pathogenesis. Our work also highlights the utility of combining quantitative proteomics and bacterial genetics for uncovering the functional roles of transcription factors and likely other uncharacterized proteins as well.