EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, degrades intestinal mucin.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of morbidity and mortality due to infectious diarrhea in developing countries for which there is presently no effective vaccine. A central challenge in ETEC vaccinology has been the identification of conserved surface antigens to formulate a broadly protective vaccine. Here, we demonstrate that EatA, an immunogenic secreted serine protease of ETEC, contributes to virulence by degrading MUC2, the major protein present in the small intestinal mucous layer, and that removal of this barrier in vitro accelerates toxin access to the enterocyte surface. In addition, we demonstrate that vaccination with the recombinant secreted passenger domain of EatA (rEatAp) elicits high titers of antibody and is protective against intestinal infection with ETEC. These findings may have significant implications for development of both subunit and live-attenuated vaccines against ETEC and other enteric pathogens, including Shigella flexneri, that express similar proteins.
Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.
Pardeep
P
Kumar
Qingwei
Q
Luo
Tim J
TJ
Vickers
Alaullah
A
Sheikh
Warren G
WG
Lewis
James M
JM
Fleckenstein
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D054307:Enterotoxigenic Escherichia coli / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000276:immunology / Q000378:metabolism*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D055262:Mucin-2 / Q000378:metabolism*; D010447:Peptide Hydrolases; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C524625:MUC2 protein, human; D055262:Mucin-2; D022223:Vaccines, Subunit; D037521:Virulence Factors; C483578:EatA protein, E coli; D010447:Peptide Hydrolases