biostudies-literatureGu HJiangsu Provincial Commission of Health and Family PlanningNational Natural Science Foundation of ChinaNatural Science Foundation of Jiangsu Provincee1010005https://www.ebi.ac.uk/biostudies/studies/S-EPMC8550376biostudies-literatureUnknown17(10)Uropathogenic Escherichia coli (UPEC) deploy an array of virulence factors to successfully establish urinary tract infections. Hemolysin is a pore-forming toxin, and its expression correlates with the severity of UPEC infection. Two-component signaling systems (TCSs) are a major mechanism by which bacteria sense environmental cues and respond by initiating adaptive responses. Here, we began this study by characterizing a novel TCS (C3564/C3565, herein renamed orhK/orhR for oxidative resistance and hemolysis kinase/regulator) that is encoded on a UPEC pathogenicity island, using bioinformatic and biochemical approaches. A prevalence analysis indicates that orhK/orhR is highly associated with the UPEC pathotype, and it rarely occurs in other E. coli pathotypes tested. We then demonstrated thPLoS pathogensA previously uncharacterized two-component signaling system in uropathogenic Escherichia coli coordinates protection against host-derived oxidative stress with activation of hemolysin-mediated host cell pyroptosis.PMC8550376BK2019112231902242H2019085Li GGu HLuo JZhang XHu XCai XCai WfalseA previously uncharacterized two-component signaling system in uropathogenic Escherichia coli coordinates protection against host-derived oxidative stress with activation of hemolysin-mediated host cell pyroptosis.Uropathogenic Escherichia coli (UPEC) deploy an array of virulence factors to successfully establish urinary tract infections. Hemolysin is a pore-forming toxin, and its expression correlates with the severity of UPEC infection. Two-component signaling systems (TCSs) are a major mechanism by which bacteria sense environmental cues and respond by initiating adaptive responses. Here, we began this study by characterizing a novel TCS (C3564/C3565, herein renamed orhK/orhR for oxidative resistance and hemolysis kinase/regulator) that is encoded on a UPEC pathogenicity island, using bioinformatic and biochemical approaches. A prevalence analysis indicates that orhK/orhR is highly associated with the UPEC pathotype, and it rarely occurs in other E. coli pathotypes tested. We then demonstrated th2021-01-01T00:00:00Z2021 Oct2026-05-08T02:24:51.478Z2025-04-19T10:31:04.798ZS-EPMC85503763465321810.1371/journal.ppat.1010005