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Infect. Immun. doi:10.1128/IAI.01304-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The EtpA exoprotein of Enterotoxigenic Escherichia coli promotes intestinal colonization and is a protective antigen in an experimental murine infection model

Koushik Roy, David Hamilton, Kenneth P. Allen, Mildred P. Randolph, and James M. Fleckenstein*

Medicine Service, Veterans Affairs Medical Center; Departments of Medicine, Comparative Medicine, and Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN

* To whom correspondence should be addressed. Email: jflecke1{at}tennessee.edu.


   Abstract

The enterotoxigenic Escherichia coli (ETEC) are major causes of morbidity and mortality due to diarrheal illness in developing countries. At present, there is no broadly protective vaccine for this diverse group of pathogens. The EtpA protein, identified in ETEC H10407 in a recent search for candidate immunogens, is a large glycosylated exoprotein secreted via two-partner secretion (TPS). Similar to structurally related molecules, EtpA functions in vitro as an adhesin. The studies reported here employ a recently developed murine model of ETEC intestinal colonization to examine the immunogenicity and protective efficacy of EtpA. Here we report that mice repeatedly exposed to ETEC are protected from subsequent colonization, and that they mount immune responses to both EtpA and its presumed two-partner secretion transporter (EtpB) during the course of experimental infection. Furthermore, isogenic etpA deletion mutants were impaired in colonization of mice, and intranasal immunization of mice with recombinant EtpA conferred protection against ETEC H10407 in this model. Together, these data suggest that EtpA is required for optimal colonization of the intestine paralleling previous in vitro studies demonstrating its role in adherence. EtpA and other TPS proteins may be viable targets for ETEC vaccine development.







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