SEVERAL CARCINOEMBRYONIC ANTIGENS (CD66) SERVE AS RECEPTORS FOR GONOCOCCAL OPACITY PROTEINS

Neisseria gonorrhoeae (GC) is a human pathogen that adheres to and inv ades genital surfaces. Although pill are required for the initial adhe rence, the interaction of GC with epithelial cells is also promoted by a family of outer membrane proteins, the opacity (Opal proteins such as OpaA protein from strain MS11. Studies have demonstrated that the i nteraction of the OpaA GC with epithelial cells involves binding to he paran sulfate attached to syndecan receptors. However, other Opa prote ins interact with CEA gene family member 1 (CGM1) or biliary glycoprot ein (BGP), members of the CD66 antigen family. In this study, we demon strate that, in addition, the 180-kD carcinoembryonic antigen (CEA) is a receptor for Opa proteins. This conclusion was based on the followi ng observations. First, transfected HeLa cells expressing CEA (HeLa-CE A) and the CEA-expressing colon cancer cell Line (LS 174T) bound and s ubsequently engulfed the Opa(+) bacteria. These interactions were inhi bited by anti-CEA antibody, but could not be inhibited by addition of heparin. Furthermore, Opal E. roll directly bound purified CEA. We als o compared the adherence and invasion by Opa(+) bacteria of CD66 trans fected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa-CE A, and HeLa-Neo serving as negative control. Using Opal as the prototy pe, the relative ability of the transfected HeLa cell lines to support adherence was (CEA = BGPa >CGM1a >NCA much greater than CGM6 = Neo). The ability to mediate invasion of the transfectant cells was (CGM1a > CEA >BGPa >NCA >CGM6 = Neo). Among the Opa proteins tested, OpaC prove d to be bifunctional, able to mediate adherence to both syndecan recep tors and to CD66 antigens.