An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins.

Maddocks, O. D. K. , Scanlon, K. M. and Donnenberg, M. S. (2013) An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins. mBio, 4(3), e00152-13. (doi: 10.1128/mBio.00152-13) (PMID:23781066) (PMCID:PMC3684829)

Abstract

Enteropathogenic Escherichia coli (EPEC) is an attaching and effacing (A/E) human pathogen that causes diarrhea during acute infection, and it can also sustain asymptomatic colonization. A/E E. coli depletes host cell DNA mismatch repair (MMR) proteins in colonic cell lines and has been detected in colorectal cancer (CRC) patients. However, until now, a direct link between infection and host mutagenesis has not been fully demonstrated. Here we show that the EPEC-secreted effector protein EspF is critical for complete EPEC-induced depletion of MMR proteins. The mechanism of EspF activity on MMR protein was posttranscriptional and dependent on EspF mitochondrial targeting. EPEC infection also induced EspF-independent elevation of host reactive oxygen species levels. Moreover, EPEC infection significantly increased spontaneous mutation frequency in host cells, and this effect was dependent on mitochondrially targeted EspF. Taken together, these results support the hypothesis that A/E E. coli can promote colorectal carcinogenesis in humans.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maddocks, Professor Oliver
• Authors: Maddocks, O. D. K., Scanlon, K. M., and Donnenberg, M. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: mBio
• Publisher: American Society for Microbiology
• ISSN: 2150-7511
• ISSN (Online): 2150-7511
• Copyright Holders: Copyright © 2013 Maddocks et al.
• First Published: First published in mBIO 4(3):e00152-13
• Publisher Policy: Reproduced under a creative commons license