The OmpU outer membrane protein, a potential adherence factor of Vibrio cholerae.
Expression of the OmpU outer membrane protein of Vibrio cholerae is positively regulated by toxR, which also regulates critical virulence factors such as cholera toxin and the toxin-coregulated pilus colonization factor. In this study, we have characterized the 38-kDa OmpU protein and investigated its role in the adhesion of V. cholerae to mammalian cells. The amino-terminal sequence of OmpU has similarity with the sequences of Haemophilus influenzae HMW1 and HMW2 adhesins, which, in turn, also have similarity with the sequence of Bordetella pertussis filamentous hemagglutinin. A monoclonal antibody directed against FHA recognized both V. cholerae OmpU and Escherichia coli OmpA, and polyclonal anti-OmpU antibodies recognized FHA and E. coli OmpA, suggesting the existence of common epitopes among these proteins. OmpU was strongly recognized by convalescent-phase serum from volunteers experimentally infected with virulent V. cholerae strains, indicating that OmpU is immunogenic and produced in vivo. OmpU selectively bound to fibronectin and to an arginine-glycine-asparagine (RGD) tripeptide but not to other matrix glycoproteins tested such as collagen or laminin. Antibodies directed against OmpU or their F(ab)2 fragments completely inhibited adhesion of several V. cholerae strains to HeLa, HEp-2, Caco-2, and Henle 407 epithelial cells and also inhibited intestinal colonization and conferred protection in newborn mice against both biotypes (El Tor and classical) of V. cholerae O1. Collectively, these data indicate that OmpU has adhesive properties which may play a role in the pathogenesis of cholera.
Sperandio
V
V
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA.
Girón
J A
JA
Silveira
W D
WD
Kaper
J B
JB
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology*; D002478:Cells, Cultured; D002771:Cholera / Q000517:prevention & control*; D004847:Epithelial Cells; D005353:Fibronectins / Q000378:metabolism; D007116:Immunization, Passive; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014734:Vibrio cholerae / Q000737:chemistry* / Q000276:immunology
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D005353:Fibronectins; C096349:OmpU protein, Vibrio cholerae