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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 (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.
National Category
Microbiology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-29102 (URN)10.1016/j.micpath.2010.04.001 (DOI)000280267500001 ()2-s2.0-77954660611 (Scopus ID)
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"
2013-09-302013-09-302022-07-13Bibliographically approved