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Nitric oxide and bacteria-host interactions in Escherichia coli urinary tract infection
University of Kalmar, School of Pure and Applied Natural Sciences. (Marine Microbial Ecology)
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: urn:nbn:se:lnu:diva-29096ISBN: 978-91-85993-01-7 (print)OAI: oai:DiVA.org:lnu-29096DiVA: diva2:652303
Public defence
2008-04-25, Västergårds hörsal, Smålandsgatan 26b, Kalmar, 10:00
Opponent
Supervisors
Available from: 2013-11-20 Created: 2013-09-30 Last updated: 2017-01-24Bibliographically approved
List of papers
1. Uropathogenic Escherichia coli and tolerance to nitric oxide: The role of flavohemoglobin
Open this publication in new window or tab >>Uropathogenic Escherichia coli and tolerance to nitric oxide: The role of flavohemoglobin
2006 (English)In: The journal of urology, Vol. 175 (2), 749-753 p.Article in journal (Refereed) Published
National Category
Natural Sciences
Research subject
Biomedical Sciences, Pharmacology; Natural Science, Microbiology; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-691 (URN)
Available from: 2010-04-01 Created: 2010-04-01 Last updated: 2013-11-20Bibliographically approved
2. Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – implications for urinary tract infection
Open this publication in new window or tab >>Role of flavohemoglobin in combating nitrosative stress in uropathogenic Escherichia coli – implications for urinary tract infection
Show others...
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.

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)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"

Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
3. The effect of nitric oxide on adherence of P-fimbriated uropathogenic Escherichia coli to human renal epithelial cells
Open this publication in new window or tab >>The effect of nitric oxide on adherence of P-fimbriated uropathogenic Escherichia coli to human renal epithelial cells
2010 (English)In: British Journal of Urology, ISSN 0007-1331, E-ISSN 1365-2176, Vol. 105, no 12, 1726-1731 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES

To examine the effect of nitric oxide (NO), an endogenous component of the host defence in urinary tract infection, on the adherence of P-fimbriated uropathogenic Escherichia coli (UPEC) to human renal epithelial cells.

MATERIALS AND METHODS

Two wild-type UPEC strains (AD110 and IA2) and the P-fimbriated recombinant strain HB101pPIL-75 were used. Bacteria were allowed to adhere to the human renal epithelial cell line A498 and attachment was evaluated in the absence or presence of the NO donor DETA/NONOate (1 mm). Total RNA was extracted from NO-exposed bacteria in static urine cultures, followed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of the papG gene that encodes the P-fimbriae adhesin PapG.

RESULTS

Bacterial adherence to A498 cells was fimbriae-dependent and the ability to agglutinate human P1 positive erythrocytes confirmed that the used strains were P-fimbriated. UPEC strains AD110 and IA2 attached by a mean of 8 bacteria/cell and 20 bacteria/cell, respectively. In the presence of DETA/NONOate, the attachment of AD110 and IA2 to A498 cells was significantly reduced by a mean (sem) of 34 (3.9)% and 45 (14)%, respectively. The expression of papG was decreased after DETA/NONOate exposure as shown by semiquantitative RT-PCR.

CONCLUSION

NO disrupted functional adhesion of P-fimbriated UPEC to kidney epithelial cells, suggesting that NO-production from epithelial cells in the urinary tract may limit bacterial colonization at the mucosal surface. The reduced adherence may involve transcriptional effects of NO on papG expression, but further studies are needed to establish the underlying mechanisms.

National Category
Microbiology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-29101 (URN)10.1111/j.1464-410X.2009.08986.x (DOI)
Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
4. The influence of uropathogenic Escherichia coli and proinflammatory cytokines on the inducible nitric oxide synthase response in human kidney epithelial cells
Open this publication in new window or tab >>The influence of uropathogenic Escherichia coli and proinflammatory cytokines on the inducible nitric oxide synthase response in human kidney epithelial cells
2005 (English)In: The journal of urology, Vol. 173 (3), 1000-1003 p.Article in journal (Refereed) Published
Research subject
Biomedical Sciences, Pharmacology
Identifiers
urn:nbn:se:lnu:diva-688 (URN)
Available from: 2010-04-01 Created: 2010-04-01 Last updated: 2013-11-20Bibliographically approved
5. Upregulation of Heme Oxygenase-1 as a Host Mechanism for Protection Against Nitric Oxide–induced Damage in Human Renal Epithelial Cells
Open this publication in new window or tab >>Upregulation of Heme Oxygenase-1 as a Host Mechanism for Protection Against Nitric Oxide–induced Damage in Human Renal Epithelial Cells
2009 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 73, no 5, 749-753 p.Article in journal (Refereed) Published
Abstract [en]

ObjectivesTo examine whether urinary tract infection–associated stimuli could regulate heme oxygenase-1 (HO-1) expression and to asses the significance of HO-1 in protecting urinary tract epithelial cells against nitric oxide (NO)-induced damage.

MethodsHeme oxygenase-1 expression was investigated in the human renal epithelial cell line A498 in response to the uropathogenic Escherichia coli (UPEC) strain IA2, the NO-donor DETA/NONOate (DETA/NO), and proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interferon-γ) using reverse transcriptase polymerase chain reaction and Western blot analysis. Cell viability was examined by the trypan blue exclusion test and light microscopy.

ResultsThe HO-1 inducer hemin and DETA/NO increased HO-1 expression in A498 cells, and glutathione depletion further increased HO-1 expression in response to DETA/NO and hemin. Stimulation with a UPEC strain or cytokines did not upregulate HO-1 expression. The cytokines induced inducible NO synthase expression and caused an increase in nitrite production. Hemin significantly decreased cytokine-induced NO production (P <0.001). DETA/NO decreased the cell viability by approximately 75%, but hemin was able to attenuate DETA/NO-induced cell damage.

ConclusionsThe expression of HO-1 increased in human renal epithelial cells in response to NO, and the expression was further enhanced in glutathione-depleted cells. The bacteria per se or proinflammatory cytokines were not able to upregulate HO-1. Heme oxygenase-1 protects the cells against NO by feedback inhibition of NO production and by decreasing cell damage.

National Category
Microbiology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-29099 (URN)10.1016/j.urology.2008.02.027 (DOI)
Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved

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