Dynamin2- and endothelial nitric oxide synthaseâ regulated invasion of bladder epithelial cells by uropathogenic Escherichia coli
Authors
Wang, ZhiminHumphrey, Ceba
Frilot, Nicole
Wang, Gaofeng
Nie, Zhongzhen
Moniri, Nader H.
Daaka, Yehia
Issue Date
2011-01-10
Metadata
Show full item recordAbstract
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):101-110ae974a485f413a2113503eed53cd6c53
10.1083/jcb.201003027