title: The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide.
abstract: When Escherichia coli is exposed to redox-cycling drugs, its SoxR transcription factor is activated by oxidation of its [2Fe-2S] cluster. In aerobic cells these drugs generate superoxide, and because superoxide dismutase (SOD) is a member of the SoxRS regulon, superoxide was initially thought to be the activator of SoxR. Its many-gene regulon was therefore believed to comprise a defence against superoxide stress. However, we found that abundant superoxide did not effectively activate SoxR in an SOD⁻ mutant, that overproduced SOD could not suppress activation by redox-cycling drugs, and that redox-cycling drugs were able to activate SoxR in anaerobic cells as long as alternative respiratory acceptors were provided. Thus superoxide is not the signal that SoxR senses. Indeed, redox-cycling drugs directly oxidized the cluster of purified SoxR in vitro, while superoxide did not. Redox-cycling drugs are excreted by both bacteria and plants. Their toxicity does not require superoxide, as they poisoned E. coli under anaerobic conditions, in part by oxidizing dehydratase iron-sulfur clusters. Under these conditions SoxRS induction was protective. Thus it is physiologically appropriate that the SoxR protein directly senses redox-cycling drugs rather than superoxide.
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Mianzhi
authors.initials: M
authors.lastname: Gu
authors.forename: James A
authors.initials: JA
authors.lastname: Imlay
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology*; D010269:Paraquat / Q000494:pharmacology*; D018085:Regulon; D013481:Superoxides / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D013481:Superoxides; C070724:SoxR protein, Bacteria; C070725:SoxS protein, E coli; D008773:Methylphenazonium Methosulfate; D024483:Vitamin K 3; D010269:Paraquat