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The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection

Shepherd, Mark, Achard, Maud E.S., Idris, Adi, Totsika, Makrina, Phan, Minh-Duy, Peters, Kate M., Sarkar, Sohinee, Ribeiro, Cláudia, Holyoake, Louise V, Ladakis, Dimitrios, and others. (2016) The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection. Scientific Reports, 6 . Article Number 35285. ISSN 2045-2322. (doi:10.1038/srep35285) (KAR id:57324)

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.

Item Type: Article
DOI/Identification number: 10.1038/srep35285
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Shepherd
Date Deposited: 16 Sep 2016 12:31 UTC
Last Modified: 19 Oct 2020 15:22 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/57324 (The current URI for this page, for reference purposes)

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