The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli.
Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.
From the Department of Molecular, Cellular, and Developmental Biology.
Benjamin W
BW
Parker
From the Department of Molecular, Cellular, and Developmental Biology.
Emily A
EA
Schwessinger
From the Department of Molecular, Cellular, and Developmental Biology; the Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan 48109. Electronic address: ujakob@umich.edu.
Ursula
U
Jakob
From the Department of Molecular, Cellular, and Developmental Biology. Electronic address: mikegray@umich.edu.
Michael J
MJ
Gray
D051777:AraC Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D051777:AraC Transcription Factor; C497371:AraC protein, E coli; D029968:Escherichia coli Proteins; D016877:Oxidants; D015534:Trans-Activators; D006997:Hypochlorous Acid
Bacterial Signal Transduction; Escherichia coli; Hypochlorous Acid (HOCl); Oxidative Stress; Reactive Chlorine Species (RCS); Redox Signaling; Transcription Regulation; YkgD