title: Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons.
abstract: The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts. Here we report the identification of an enzymatic system, MsrPQ, repairing proteins containing methionine sulfoxide in the bacterial cell envelope, a compartment particularly exposed to the reactive species of oxygen and chlorine generated by the host defence mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid, a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. A remarkable feature of MsrPQ is its capacity to reduce both rectus (R-) and sinister (S-) diastereoisomers of methionine sulfoxide, making this oxidoreductase complex functionally different from previously identified Msrs. The discovery that a large class of bacteria contain a single, non-stereospecific enzymatic complex fully protecting methionine residues from oxidation should prompt a search for similar systems in eukaryotic subcellular oxidizing compartments, including the endoplasmic reticulum.
authors.affiliation: WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.|Brussels Center for Redox Biology, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gennaris
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ezraty
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Henry
authors.affiliation: WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.|Brussels Center for Redox Biology, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Rym
authors.initials: R
authors.lastname: Agrebi
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vergnes
authors.affiliation: Aix-Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oheix
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Bos
authors.affiliation: WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.|Brussels Center for Redox Biology, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Pauline
authors.initials: P
authors.lastname: Leverrier
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Leon
authors.initials: L
authors.lastname: Espinosa
authors.affiliation: WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.|Brussels Center for Redox Biology, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szewczyk
authors.affiliation: de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.affiliation: Aix-Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Iranzo
authors.affiliation: WELBIO, Avenue Hippocrate 75, 1200 Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75, 1200 Brussels, Belgium.|Brussels Center for Redox Biology, Avenue Hippocrate 75, 1200 Brussels, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Collet
authors.affiliation: Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Barras
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D002713:Chlorine / Q000378:metabolism; D004579:Electron Transport; D004583:Electrons; D006090:Gram-Negative Bacteria / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000378:metabolism; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D019897:Periplasm / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; D002713:Chlorine; D006997:Hypochlorous Acid; D008715:Methionine; D051150:Methionine Sulfoxide Reductases; C013111:methionine sulfoxide