SamT, a novel peptide modulator of a two-component system revealed by the specific activation of a small RNA in...

Small regulatory RNAs (sRNAs) are major post-transcriptional regulators in bacteria and, together with transcriptional regulators such as the two-component systems (TCSs), participate in the rapid adaptation of these microorganisms to changing environments. Several examples of paralogous sRNAs with overlapping functions have been reported, which could in theory integrate different environmental cues. Consistent with this idea, we have identified the acid-responsive RstB-RstA TCS, important for virulence of multiple bacterial species, as a specific multicopy activator of the Escherichia coli OmrB sRNA, but not of the paralogous sRNA OmrA. Further characterization of this regulation unexpectedly revealed the asr-ydgU operon, itself a target of RstB-RstA, as a dual modulator of this TCS via two opposite effects. First, the 27 amino acid YdgU small protein exerts a negative feedback by directly interacting with RstB, while Asr independently mediates a positive feedback. Hence, in addition to identifying a specific regulator for OmrB, these results provide a new example of retro-control of a TCS, here RstB-RstA, by one of its direct targets. They further highlight the major role of small proteins in controlling TCS activity and ydgU gene was thus renamed samT, for Small Acid-responsive Modulator of the RstB-RstA TCS.