title: The Terminal Oxidase Cytochrome bd Promotes Sulfide-resistant Bacterial Respiration and Growth.
abstract: Hydrogen sulfide (H2S) impairs mitochondrial respiration by potently inhibiting the heme-copper cytochrome c oxidase. Since many prokaryotes, including Escherichia (E.) coli, generate H2S and encounter high H2S levels particularly in the human gut, herein we tested whether bacteria can sustain sulfide-resistant O2-dependent respiration. E. coli has three respiratory oxidases, the cyanide-sensitive heme-copper bo3 enzyme and two bd oxidases much less sensitive to cyanide. Working on the isolated enzymes, we found that, whereas the bo3 oxidase is inhibited by sulfide with half-maximal inhibitory concentration IC50 = 1.1 ± 0.1 μM, under identical experimental conditions both bd oxidases are insensitive to sulfide up to 58 μM. In E. coli respiratory mutants, both O2-consumption and aerobic growth proved to be severely impaired by sulfide when respiration was sustained by the bo3 oxidase alone, but unaffected by ≤200 μM sulfide when either bd enzyme acted as the only terminal oxidase. Accordingly, wild-type E. coli showed sulfide-insensitive respiration and growth under conditions favouring the expression of bd oxidases. In all tested conditions, cyanide mimicked the functional effect of sulfide on bacterial respiration. We conclude that bd oxidases promote sulfide-resistant O2-consumption and growth in E. coli and possibly other bacteria. The impact of this discovery is discussed.
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur- Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Forte
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russian Federation.
authors.forename: Vitaliy B
authors.initials: VB
authors.lastname: Borisov
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur- Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Micol
authors.initials: M
authors.lastname: Falabella
authors.affiliation: Metabolism &Genetics Group, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Portugal.
authors.forename: Henrique G
authors.initials: HG
authors.lastname: Colaço
authors.affiliation: Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Mariana
authors.initials: M
authors.lastname: Tinajero-Trejo
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, United Kingdom.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Poole
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: João B
authors.initials: JB
authors.lastname: Vicente
authors.affiliation: Department of Biochemical Sciences and Istituto Pasteur- Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sarti
authors.affiliation: CNR Institute of Molecular Biology and Pathology, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuffrè
mesh_terms: D000332:Aerobiosis / Q000187:drug effects / Q000235:genetics; D003486:Cyanides / Q000494:pharmacology; D003573:Cytochrome b Group; D003580:Cytochromes / Q000172:deficiency / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D007700:Kinetics; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D010100:Oxygen / Q000494:pharmacology
chemical_list: D003486:Cyanides; D003573:Cytochrome b Group; D003580:Cytochromes; D045222:Electron Transport Chain Complex Proteins; D029968:Escherichia coli Proteins; D007527:Isoenzymes; C083850:cytochrome bo3, E coli; D010088:Oxidoreductases; C040077:cytochrome bd terminal oxidase complex, E coli; D010100:Oxygen; D006862:Hydrogen Sulfide