Known Bioactive Small Molecules Probe the Function of a Widely Conserved but Enigmatic Bacterial ATPase, YjeE

Escherichia coli YjeE is a broadly conserved bacterial ATPase of unknown function that has been widely characterized as essential. Here, the transcriptional regulation of the promoter of yjeE (P(yjeE)) was probed using a luciferase reporter and 172 antibiotics of diverse mechanisms. Norfloxacin and other fluorquinolones were found to be the most potent activator of P(yjeE) through binding to DNA gyrase. The stimulation of P(yjeE) by norfloxacin was most impacted by lesions in two-component signal transduction systems with roles in respiration, central metabolism, and oxidative stress responses. This suggested that YjeE may have a critical role in aerobic metabolism. Remarkably, YjeE was found to be dispensable when cells were grown in the absence of oxygen. To the best of our knowledge, these findings represent the first definitive phenotypes for this enigmatic protein.