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Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – implications for urinary tract infection
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Ecology and Evolution in Microbial Model Systems, EEMiS. (Marine Microbial Ecology)
Institute of Molecular Medicine and Surgery, Section of Urology, Karolinska Institute, Stockholm, Sweden.
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
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2010 (English)In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 49, no 3, 59-66 p.Article 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 (J96Δhmp) knockout mutant of UPEC strain J96 was constructed using single-gene deletion. The viability of J96Δhmp was significantly reduced (P < 0.001) compared to the wild-type strain after exposure to the NO-donor DETA/NO. The NO consumption in J96Δhmp 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, 59-66 p.
National Category
Microbiology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-29102DOI: 10.1016/j.micpath.2010.04.001Scopus ID: 2-s2.0-77954660611OAI: oai:DiVA.org:lnu-29102DiVA: diva2:652312
Note

Ingår i avhandlingen "Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection" under titeln "Flavohemoglobin protects uropathogenic Escherichia coli against nitrosative stress; implication for urovirulence"

Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection
Open this publication in new window or tab >>Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Kalmar: Högskolan i Kalmar, 2008. 53 p.
Series
Dissertation series / University of Kalmar, Faculty of Natural Science, ISSN 1650-2779 ; 51
National Category
Microbiology in the medical area
Research subject
Biomedical Sciences, Pharmacology
Identifiers
urn:nbn:se:lnu:diva-29096 (URN)978-91-85993-01-7 (ISBN)
Public defence
2008-04-25, Västergårds hörsal, Smålandsgatan 26b, Kalmar, 10:00
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Supervisors
Available from: 2013-11-20 Created: 2013-09-30 Last updated: 2017-01-24Bibliographically approved

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