Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli: implications for urinary tract infection

Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli : implications for urinary tract infection

Svensson, Lovisa (author): Linnéuniversitetet,Institutionen för naturvetenskap, NV,Marine Microbial Ecology

Säve, Susanne (author): Linnéuniversitetet,Institutionen för naturvetenskap, NV

Persson, Katarina (author): Linnéuniversitetet,Örebro universitet,Hälsoakademin,Institutionen för naturvetenskap, NV,Örebro University

(creator_code:org_t)

Elsevier BV, 2010
2010
English.
In: Microbial Pathogenesis. - : Elsevier BV. - 0882-4010 .- 1096-1208. ; 49:3, s. 59-66

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Abstract Subject headings

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.

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

By the author/editor: Svensson, Lovisa; Poljakovic, Mirj ...; Säve, Susanne; Gilberthorpe, Ni ...; Schön, Thomas; Strid, Sigge; show more...; Corker, Hazel; Poole, Robert K.; Persson, Katarin ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

By the university: Örebro University; Linnaeus University; Karolinska Institutet

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