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  • 1.
    Svensson, Lovisa
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Poljakovic, Mirjana
    Karolinska Institutet.
    Säve, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Gilberthorpe, Nicola
    University of Sheffield, UK.
    Schön, Thomas
    Kalmar County Hospital.
    Strid, Sigge
    Stensö Health Center, Kalmar County Council.
    Corker, Hazel
    University of Sheffield, UK.
    Poole, Robert K.
    University of Sheffield, UK.
    Persson, Katarina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Örebro University.
    Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – implications for urinary tract infection2010In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 49, no 3, p. 59-66Article in journal (Refereed)
    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.

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