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Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – implications for urinary tract infection
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV. (Marine Microbial Ecology;Ctr Ecol & Evolut Microbial Model Syst EEMiS)
Karolinska Institutet.
Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
University of Sheffield, UK.
Vise andre og tillknytning
2010 (engelsk)Inngår i: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 49, nr 3, s. 59-66Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2010. Vol. 49, nr 3, s. 59-66
HSV kategori
Forskningsprogram
Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:lnu:diva-29102DOI: 10.1016/j.micpath.2010.04.001Scopus ID: 2-s2.0-77954660611OAI: oai:DiVA.org:lnu-29102DiVA, id: diva2:652312
Merknad

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"

Tilgjengelig fra: 2013-09-30 Laget: 2013-09-30 Sist oppdatert: 2018-10-24bibliografisk kontrollert
Inngår i avhandling
1. Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection
Åpne denne publikasjonen i ny fane eller vindu >>Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection
2008 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
sted, utgiver, år, opplag, sider
Kalmar: Högskolan i Kalmar, 2008. s. 53
Serie
Dissertation series / University of Kalmar, Faculty of Natural Science, ISSN 1650-2779 ; 51
HSV kategori
Forskningsprogram
Biomedicinsk vetenskap, Farmakologi
Identifikatorer
urn:nbn:se:lnu:diva-29096 (URN)978-91-85993-01-7 (ISBN)
Disputas
2008-04-25, Västergårds hörsal, Smålandsgatan 26b, Kalmar, 10:00
Opponent
Veileder
Tilgjengelig fra: 2013-11-20 Laget: 2013-09-30 Sist oppdatert: 2018-01-11bibliografisk kontrollert

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