Dynamin2- and endothelial nitric oxide synthaseâ regulated invasion of bladder epithelial cells by uropathogenic Escherichia coli

Hdl Handle:
http://hdl.handle.net/10675.2/623
Title:
Dynamin2- and endothelial nitric oxide synthaseâ regulated invasion of bladder epithelial cells by uropathogenic Escherichia coli
Authors:
Wang, Zhimin; Humphrey, Ceba; Frilot, Nicole; Wang, Gaofeng; Nie, Zhongzhen; Moniri, Nader H.; Daaka, Yehia
Abstract:
Invasion of bladder epithelial cells by uropathogenic Escherichia coli (UPEC) contributes to antibiotic-resistant and recurrent urinary tract infections (UTIs), but this process is incompletely understood. In this paper, we provide evidence that the large guanosine triphosphatase dynamin2 and its partner, endothelial nitric oxide (NO) synthase (NOS [eNOS]), mediate bacterial entry. Overexpression of dynamin2 or treatment with the NO donor S-nitrosothiols increases, whereas targeted reduction of endogenous dynamin2 or eNOS expression with ribonucleic acid interference impairs, bacterial invasion. Exposure of mouse bladder to small molecule NOS inhibitors abrogates infection of the uroepithelium by E. coli, and, concordantly, bacteria more efficiently invade uroepithelia isolated from wild-type compared with eNOSâ /â mice. E. coli internalization promotes rapid phosphorylation of host cell eNOS and NO generation, and dynamin2 S-nitrosylation, a posttranslational modification required for the bacterial entry, also increases during E. coli invasion. These findings suggest that UPEC escape urinary flushing and immune cell surveillance by means of eNOS-dependent dynamin2 S-nitrosylation and invasion of host cells to cause recurrent UTIs.
Citation:
J Cell Biol. 2011 Jan 10; 192(1):101-110
Issue Date:
10-Jan-2011
URI:
http://hdl.handle.net/10675.2/623
DOI:
10.1083/jcb.201003027
PubMed ID:
21220511
PubMed Central ID:
PMC3019553
Type:
Article
ISSN:
1540-8140
Appears in Collections:
Department of Pathology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Zhiminen_US
dc.contributor.authorHumphrey, Cebaen_US
dc.contributor.authorFrilot, Nicoleen_US
dc.contributor.authorWang, Gaofengen_US
dc.contributor.authorNie, Zhongzhenen_US
dc.contributor.authorMoniri, Nader H.en_US
dc.contributor.authorDaaka, Yehiaen_US
dc.date.accessioned2012-10-26T16:26:54Z-
dc.date.available2012-10-26T16:26:54Z-
dc.date.issued2011-01-10en_US
dc.identifier.citationJ Cell Biol. 2011 Jan 10; 192(1):101-110en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid21220511en_US
dc.identifier.doi10.1083/jcb.201003027en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/623-
dc.description.abstractInvasion of bladder epithelial cells by uropathogenic Escherichia coli (UPEC) contributes to antibiotic-resistant and recurrent urinary tract infections (UTIs), but this process is incompletely understood. In this paper, we provide evidence that the large guanosine triphosphatase dynamin2 and its partner, endothelial nitric oxide (NO) synthase (NOS [eNOS]), mediate bacterial entry. Overexpression of dynamin2 or treatment with the NO donor S-nitrosothiols increases, whereas targeted reduction of endogenous dynamin2 or eNOS expression with ribonucleic acid interference impairs, bacterial invasion. Exposure of mouse bladder to small molecule NOS inhibitors abrogates infection of the uroepithelium by E. coli, and, concordantly, bacteria more efficiently invade uroepithelia isolated from wild-type compared with eNOSâ /â mice. E. coli internalization promotes rapid phosphorylation of host cell eNOS and NO generation, and dynamin2 S-nitrosylation, a posttranslational modification required for the bacterial entry, also increases during E. coli invasion. These findings suggest that UPEC escape urinary flushing and immune cell surveillance by means of eNOS-dependent dynamin2 S-nitrosylation and invasion of host cells to cause recurrent UTIs.en_US
dc.rights© 2011 Wang et al.en_US
dc.titleDynamin2- and endothelial nitric oxide synthaseâ regulated invasion of bladder epithelial cells by uropathogenic Escherichia colien_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3019553en_US
dc.contributor.corporatenameDepartment of Pathology-

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