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The EtpA Exoprotein of Enterotoxigenic Escherichia coli Promotes Intestinal Colonization and Is a Protective Antigen in an Experimental Model of Murine Infection

Koushik Roy,² David Hamilton,³ Kenneth P. Allen,^3, Mildred P. Randolph,^3, and James M. Fleckenstein^1,2,4*

Medicine Service, Veterans Affairs Medical Center,¹ Departments of Medicine,² Comparative Medicine,³ Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38104⁴

Received 25 September 2007/ Returned for modification 13 November 2007/ Accepted 7 February 2008

The enterotoxigenic Escherichia coli (ETEC) strains 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 use a recently developed murine model of ETEC intestinal colonization to examine the immunogenicity and protective efficacy of EtpA. 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 the 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, findings paralleling those of previous in vitro studies demonstrating its role in adherence. EtpA and other TPS proteins may be viable targets for ETEC vaccine development.

Published ahead of print on 19 February 2008.

Editor: V. J. DiRita

Present address: Biomedical Resource Center, Medical College of Wisconsin, Milwaukee, WI.

Present address: University of Arkansas for Medical Sciences, Little Rock, AR.