Mp. Bos et al., DIFFERENTIAL RECOGNITION OF MEMBERS OF THE CARCINOEMBRYONIC ANTIGEN FAMILY BY OPA VARIANTS OF NEISSERIA-GONORRHOEAE, Infection and immunity, 65(6), 1997, pp. 2353-2361
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.