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

Date

2011-01-10

Authors

Wang, Zhimin
Humphrey, Ceba
Frilot, Nicole
Wang, Gaofeng
Nie, Zhongzhen
Moniri, Nader H.
Daaka, Yehia

Journal Title

Journal ISSN

Volume Title

Publisher

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.

Description

Keywords

Citation

J Cell Biol. 2011 Jan 10; 192(1):101-110