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Host-Derived Nitric Oxide and Its Antibacterial Effects in the Urinary Tract
Örebro University, School of Medical Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
Örebro University, School of Medical Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
Örebro University, School of Health Sciences. (Inflammatory Response and Infection Susceptibility Centre (iRiSC))
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2018 (English)In: Advances in Microbial Physiology, ISSN 0065-2911, E-ISSN 2162-5468, Vol. 73, p. 1-62Article, review/survey (Refereed) Published
Abstract [en]

Urinary tract infection (UTI) is one of the most common bacterial infections in humans, and the majority are caused by uropathogenic Escherichia coli (UPEC). The rising antibiotic resistance among UPEC and the frequent failure of antibiotics to effectively treat recurrent UTI and catheter-associated UTI motivate research on alternative ways of managing UTI. Abundant evidence indicates that the toxic radical nitric oxide (NO), formed by activation of the inducible nitric oxide synthase, plays an important role in host defence to bacterial infections, including UTI. The major source of NO production during UTI is from inflammatory cells, especially neutrophils, and from the uroepithelial cells that are known to orchestrate the innate immune response during UTI. NO and reactive nitrogen species have a wide range of antibacterial targets, including DNA, heme proteins, iron-sulfur clusters, and protein thiol groups. However, UPEC have acquired a variety of defence mechanisms for protection against NO, such as the NO-detoxifying enzyme flavohemoglobin and the NO-tolerant cytochrome bd-I respiratory oxidase. The cytotoxicity of NO-derived intermediates is nonspecific and may be detrimental to host cells, and a balanced NO production is crucial to maintain the tissue integrity of the urinary tract. In this review, we will give an overview of how NO production from host cells in the urinary tract is activated and regulated, the effect of NO on UPEC growth and colonization, and the ability of UPEC to protect themselves against NO. We also discuss the attempts that have been made to develop NO-based therapeutics for UTI treatment.

Place, publisher, year, edition, pages
Academic Press, 2018. Vol. 73, p. 1-62
Keywords [en]
Antimicrobial factor, Flavohemoglobin, Inducible nitric oxide synthase, Nitric oxide, Nitrosative stress, Urinary bladder, Urinary tract infection, Uropathogenic E. coli
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-70674DOI: 10.1016/bs.ampbs.2018.05.001ISI: 000452097400001PubMedID: 30262107Scopus ID: 2-s2.0-85048708739OAI: oai:DiVA.org:oru-70674DiVA, id: diva2:1269510
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-17Bibliographically approved

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Svensson, LovisaDemirel, IsakSahlberg, CharlottePersson, Katarina

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