Investigating QseBC and PmrAB two-component system cross-interactions

Abstract

Bacteria use two-component system (TCS) signaling to sense and respond to their ever-changing surroundings. While most TCSs have been reported to interact solely as a cognate partner pair, one sensor kinase phosphorylating and dephosphorylating one response regulator, interactions between two-component systems grant uropathogenic E. coli the ability to finely calibrate responses to fluctuating environmental cues. Specifically, the QseBC and PmrAB two-component systems interact at both the post-translational, as well as the transcriptional level, to mediate a response to the signal ferric iron. The PmrB sensor kinase is able to phosphorylate its cognate regulator, PmrA, and non-cognate partner, QseB, in response to a ferric iron signal. Subsequent to ferric iron-mediated phosphorylation, both PmrA and QseB coordinate to regulate genes that allow the bacteria to become more tolerant to the antibiotic polymyxin B. Not only do QseBC-PmrAB interactions drive important antibiotic tolerance mechanisms, but they also provide a platform to investigate a phenomenon largely unobserved in TCS biology.