Logo image
Back
Clinical Escherichia coli isolates utilize alpha-hemolysin to inhibit in vitro epithelial cytokine production
Journal article   Open access   Peer reviewed

Clinical Escherichia coli isolates utilize alpha-hemolysin to inhibit in vitro epithelial cytokine production

David W. Hilbert, Teresa E. Paulish-Miller, Chee K. Tan, Alison J. Carey, Glen C. Ulett, Eli Mordechai, Martin E. Adelson, Scott E. Gygax and Jason P. Trama
Microbes and infection, v 14(07-Aug), pp 628-638
Jul 2012
DOI: https://doi.org/10.1016/j.micinf.2012.01.010
PMID: 22326301
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.micinf.2012.01.010View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Alpha-hemolysin Urinary tract infections Uropathogenic E. coli
Uropathogenic Escherichia coli is the primary cause of urinary tract infections, which affects over 60% of women during their lifetime. UPEC exhibits a number of virulence traits that facilitate colonization of the bladder, including inhibition of cytokine production by bladder epithelial cells. The goal of this study was to identify the mechanism of this inhibition. We observed that cytokine suppression was associated with rapid cytotoxicity toward epithelial cells. We found that cytotoxicity, cytokine suppression and alpha-hemolysin production were all tightly linked in clinical isolates. We screened a UPEC fosmid library and identified clones that gained the cytotoxicity and cytokine-suppression phenotypes. Both clones contained fosmids encoding a PAI IIJ96-like domain and expressed the alpha-hemolysin (hlyA) encoded therein. Mutation of the fosmid-encoded hly operon abolished cytotoxicity and cytokine suppression. Similarly, mutation of the chromosomal hlyCABD operon of UPEC isolate F11 also abolished these phenotypes, and they could be restored by introducing the PAI IIJ96-like domain-encoding fosmid. We also examined the role of alpha-hemolysin in cytokine production both in the murine UTI model as well as patient specimens. We conclude that E. coli utilizes alpha-hemolysin to inhibit epithelial cytokine production in vitro. Its contribution to inflammation during infection requires further study.

Metrics

8 Record Views
33 citations in Web of Science
38 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
International collaboration
Web of Science research areas
Immunology
Infectious Diseases
Microbiology
Logo image