DIFFERENTIAL RECOGNITION OF MEMBERS OF THE CARCINOEMBRYONIC ANTIGEN FAMILY BY OPA VARIANTS OF NEISSERIA-GONORRHOEAE

Opacity (Opa) protein variation in Neisseria gonorrhoeae is implicated in the pathogenesis of gonorrhea, possibly by mediating adherence and entry of the bacteria into human tissues, One particular Opa protein mediates adherence to epithelial cells through cell surface proteoglyc ans, Recently, two other eukaryotic cell receptors for Opa proteins ha ve been reported, These receptors are members of a subgroup of the car cinoembryonic (CEA) gene family that express CD66 antigens, CEA family members vary in their distribution in human tissues, In order to unde rstand whether interactions between Opa and CEA-like molecules play an y role in pathogenesis, we must investigate which CEA family members a re able to serve as Opa receptors and which Opa proteins recognize CEA -like molecules, We therefore studied HeLa cells that were stably tran sfected with five different members of the CEA family, i.e., CEA, CEA gene family member la (CGM1a), CGM6, nonspecific cross-reacting antige n (NCA), and biliary glycoprotein a (BGPa), We infected these transfec tants with all possible 11 Opa variants of gonococcal strain MS11 and determined the numbers of bacteria that were bound and internalized. T o account for proteoglycan-mediated adherence, infection assays were a lso performed in the presence of heparin, Our results show that of the 11 Opa variants of MS11, the same 4 recognized CGM1a and NCA, CGM6, h owever, was not recognized by any Opa variant of MS11, CEA was recogni zed by at least 9 of 11 Opa variants, and the BGP transfectants specif ically bound and internalized 10 of 11 Opa variants and also bound Opa -negative gonococci, Immunofluorescence experiments showed that cluste ring of CEA-like molecules occurred upon infection of HeLa transfectan ts with those Opa variants that interacted specifically with the CEA f amily member. Together these data show that CEA family members are dif ferentially recognized by gonococcal Opa variants, suggesting that thi s phenomenon may contribute to cell tropism displayed by gonococci.