title: Methionine oxidation activates a transcription factor in response to oxidative stress.
abstract: Oxidant-mediated antibacterial response systems are broadly used to control bacterial proliferation. Hypochlorite (HOCl) is an important component of the innate immune system produced in neutrophils and specific epithelia. Its antimicrobial activity is due to damaging cellular macromolecules. Little is known about how bacteria escape HOCl-inflicted damage. Recently, the transcription factor YjiE was identified that specifically protects Escherichia coli from HOCl killing. According to its function, YjiE is now renamed HypT (hypochlorite-responsive transcription factor). Here we unravel that HypT is activated by methionine oxidation to methionine sulfoxide. Interestingly, so far only inactivation of cellular proteins by methionine oxidation has been reported. Mutational analysis revealed three methionines that are essential to confer HOCl resistance. Their simultaneous substitution by glutamine, mimicking the methionine sulfoxide state, increased the viability of E. coli cells upon HOCl stress. Triple glutamine substitution generates a constitutively active HypT that regulates target genes independently of HOCl stress and permanently down-regulates intracellular iron levels. Inactivation of HypT depends on the methionine sulfoxide reductases A/B. Thus, microbial protection mechanisms have evolved along the evolution of antimicrobial control systems, allowing bacteria to survive within the host environment.
authors.affiliation: Center for Integrated Protein Science Munich, Department Chemie, Technische Universität München, 85747 Garching, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Drazic
authors.forename: Haruko
authors.initials: H
authors.lastname: Miura
authors.forename: Jirka
authors.initials: J
authors.lastname: Peschek
authors.forename: Yan
authors.initials: Y
authors.lastname: Le
authors.forename: Nina C
authors.initials: NC
authors.lastname: Bach
authors.forename: Thomas
authors.initials: T
authors.lastname: Kriehuber
authors.forename: Jeannette
authors.initials: J
authors.lastname: Winter
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002850:Chromatography, Gel; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D006997:Hypochlorous Acid / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology*; D007501:Iron / Q000378:metabolism; D013058:Mass Spectrometry; D008715:Methionine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014461:Ultracentrifugation
chemical_list: D029968:Escherichia coli Proteins; C550912:HypT protein, E coli; D012097:Repressor Proteins; D006997:Hypochlorous Acid; D008715:Methionine; D007501:Iron
keywords: LysR-type transcription factor; MsrA; MsrB; posttranslational modification