title: Dual regulation of inaA by the multiple antibiotic resistance (mar) and superoxide (soxRS) stress response systems of Escherichia coli.
abstract: The roles of the marRAB (multiple antibiotic resistance) operon and soxRS (superoxide response) genes in the regulation of inaA, an unlinked weak-acid-inducible gene, were studied. inaA expression was estimated from the beta-galactosidase activity of a chromosomal inaA1::lacZ transcriptional fusion. marR mutations that elevate marRAB transcription and engender multiple antibiotic resistance elevated inaA expression by 10- to 20-fold over that of the wild-type. Similarly, one class of inaA constitutive mutants that mapped to the mar region were multiply antibiotic resistant. Overexpression of marA alone on a multicopy plasmid caused high constitutive expression of inaA in a strain with an extensive (39-kbp) marRAB deletion. Salicylate, an inducer of marRAB and of an unidentified mar-independent antibiotic resistance system, induced inaA by 6-fold. A portion of this induction was also mar independent. Two soxRS constitutive mutants that were tested showed elevated levels of inaA. Paraquat, an inducer of the soxRS system, elevated inaA expression by 6- to 9-fold. This induction was soxRS dependent and not mar dependent, whereas induction of inaA by salicylate was not dependent on soxRS. Paraquat induced resistance to norfloxacin in the mar-deleted strain but not in a soxRS-deleted strain. Thus, induction of multiple antibiotic resistance and inaA by salicylate occurs via mar and an unidentified pathway, while induction by paraquat occurs via soxRS.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
authors.forename: J L
authors.initials: JL
authors.lastname: Rosner
authors.forename: J L
authors.initials: JL
authors.lastname: Slonczewski
mesh_terms: D019297:2,4-Dinitrophenol; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D004268:DNA-Binding Proteins; D004140:Dinitrophenols / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009643:Norfloxacin / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D012641:Selection, Genetic; D013481:Superoxides / Q000494:pharmacology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D004140:Dinitrophenols; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; C080004:MarR protein, E coli; D008565:Membrane Proteins; D012097:Repressor Proteins; D012459:Salicylates; D015534:Trans-Activators; D014157:Transcription Factors; C062144:inaA protein, Pantoea ananatis; C080003:multiple antibiotic resistance protein B; D013481:Superoxides; C070724:SoxR protein, Bacteria; C070725:SoxS protein, E coli; D009643:Norfloxacin; D020156:Salicylic Acid; D010269:Paraquat; D019297:2,4-Dinitrophenol