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Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli: implications for urinary tract infection
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2010 (English)In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 49, no 3, p. 59-66Article in journal (Refereed) Published
Abstract [en]

During the course of urinary tract infection (UTI) nitric oxide (NO) is generated as part of the host response. This study investigates the significance of the NO-detoxifying enzyme flavohemoglobin (Hmp) in protection of uropathogenic Escherichia coli (UPEC) against nitrosative stress. An hmp (J96Deltahmp) knockout mutant of UPEC strain J96 was constructed using single-gene deletion. The viability of J96Deltahmp was significantly reduced (P<0.001) compared to the wild-type strain after exposure to the NO-donor DETA/NO. The NO consumption in J96Deltahmp was significantly (P<0.001) impaired compared to J96wt. Screening UPEC isolates from patients with UTI revealed increased hmp expression in all patients. In a competition-based mouse model of UTI, the hmp mutant strain was significantly (P<0.05) out-competed by the wild-type strain. This study demonstrates, for the first time, that Hmp contributes to the protection of UPEC against NO-mediated toxicity in vitro. In addition, hmp gene expression occurs in UPEC isolates from the infected human urinary tract and UPEC that were hmp-deficient had a reduced ability to colonize the mouse urinary tract. Taken together the results suggest that NO detoxification by Hmp may be a fitness advantage factor in UPEC, and a potentially interesting target for development of novel treatment concepts for UTI.

Place, publisher, year, edition, pages
2010. Vol. 49, no 3, p. 59-66
Keyword [en]
Nitric oxide, Urinary tract infection, Flavohemoglobin, Uropathogenic Escherichia coli, Nitrosative stress
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-13465DOI: 10.1016/j.micpath.2010.04.001PubMedID: 20399845OAI: oai:DiVA.org:oru-13465DiVA: diva2:386078
Available from: 2011-01-12 Created: 2011-01-12 Last updated: 2017-12-11Bibliographically approved

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Persson, Katarina

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