title: The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection.
abstract: Nitric oxide (NO) is a toxic free radical produced by neutrophils and macrophages in response to infection. Uropathogenic Escherichia coli (UPEC) induces a variety of defence mechanisms in response to NO, including direct NO detoxification (Hmp, NorVW, NrfA), iron-sulphur cluster repair (YtfE), and the expression of the NO-tolerant cytochrome bd-I respiratory oxidase (CydAB). The current study quantifies the relative contribution of these systems to UPEC growth and survival during infection. Loss of the flavohemoglobin Hmp and cytochrome bd-I elicit the greatest sensitivity to NO-mediated growth inhibition, whereas all but the periplasmic nitrite reductase NrfA provide protection against neutrophil killing and promote survival within activated macrophages. Intriguingly, the cytochrome bd-I respiratory oxidase was the only system that augmented UPEC survival in a mouse model after 2 days, suggesting that maintaining aerobic respiration under conditions of nitrosative stress is a key factor for host colonisation. These findings suggest that while UPEC have acquired a host of specialized mechanisms to evade nitrosative stresses, the cytochrome bd-I respiratory oxidase is the main contributor to NO tolerance and host colonisation under microaerobic conditions. This respiratory complex is therefore of major importance for the accumulation of high bacterial loads during infection of the urinary tract.
authors: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom.
authors: Mark
authors: M
authors: Shepherd
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Maud E S
authors: ME
authors: Achard
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Adi
authors: A
authors: Idris
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Makrina
authors: M
authors: Totsika
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Minh-Duy
authors: MD
authors: Phan
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Kate M
authors: KM
authors: Peters
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Sohinee
authors: S
authors: Sarkar
authors: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom.
authors: Cláudia A
authors: CA
authors: Ribeiro
authors: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom.
authors: Louise V
authors: LV
authors: Holyoake
authors: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom.
authors: Dimitrios
authors: D
authors: Ladakis
authors: School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, 4222, Australia.
authors: Glen C
authors: GC
authors: Ulett
authors: Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Matthew J
authors: MJ
authors: Sweet
authors: Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, United Kingdom.
authors: Robert K
authors: RK
authors: Poole
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Alastair G
authors: AG
authors: McEwan
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Mark A
authors: MA
authors: Schembri
mesh_terms: D000818:Animals; D003573:Cytochrome b Group; D003574:Cytochrome c Group / Q000172:deficiency / Q000235:genetics; D003580:Cytochromes / Q000172:deficiency / Q000235:genetics*; D004093:Dihydropteridine Reductase / Q000235:genetics*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006420:Hemeproteins / Q000172:deficiency / Q000235:genetics*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D009569:Nitric Oxide / Q000378:metabolism; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D014552:Urinary Tract Infections / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000235:genetics* / Q000254:growth & development
chemical_list: D003573:Cytochrome b Group; D003574:Cytochrome c Group; D003580:Cytochromes; D045222:Electron Transport Chain Complex Proteins; D029968:Escherichia coli Proteins; D006420:Hemeproteins; C497162:YtfE protein, E coli; D009569:Nitric Oxide; C022302:cytochrome C-552; D010088:Oxidoreductases; D004093:Dihydropteridine Reductase; C076538:hmp protein, E coli; D009247:NADH, NADPH Oxidoreductases; C040077:cytochrome bd terminal oxidase complex, E coli