Accession Number:

AD1014505

Title:

The Modulation of Polymorphonuclear Neutrophil Function by Cytotoxic Necrotizing Factor Type-1 Uropathogenic Escherichia coli

Descriptive Note:

Technical Report

Corporate Author:

Uniformed Services University Of The Health Sciences Bethesda United States

Personal Author(s):

Report Date:

2005-09-19

Pagination or Media Count:

167.0

Abstract:

Uropathogenic Escherichia coli UPEC cause more than 85 of all urinary tract infections UTI. These infections primarily affect women, and over half of all women will experience at least one UTI in their lifetime. Animal models of UTI pathogenesis have provided some insight into the role of various UPEC virulence factors. In these animal studies, the toxin Cytotoxic Necrotizing Factor type 1 CNF1 has been shown to have a significant role in the pathogenesis of UTI. One of the most striking features ofCNF1-expressing UPEC infection in the in vivo models was magnitude of the acute inflammatory response. Compared to a cnf1 isogenic mutant, CNF1-expressing UPE Celicited an acute inflammatory response characterized by an extensive infiltration of polymorphonuclear leukocytes PMN into tissue infected with CNF1-expressing UPEC. In spite of the enhanced acute inflammatory response, the CNF1-expressing UPEC had a significant survival advantage compared to the cnf1 isogenic mutant. CNF1 is an AB toxin that deamidates the catalytically-active glutamine residue in the Rho family of small GTPases. The Rho family GTPases are intracellular signaling molecules responsible for the control of many cellular function in eukaryotic cells such as PMNs.

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Distribution Statement:

APPROVED FOR PUBLIC RELEASE