Substitutions Y34F and Q89N also produced interesting data from the point of view of pathogenesis. Whilst Q89A and Q89N appear to affect some Opa proteins by reducing receptor recognition, suggesting its potential contribution in determining tissue tropism (Virji et al., 1999) , Q89N substitution occasionally caused dramatic increase in bacterial adhesion, especially of Hi isolates. Y34F, as observed above, increased binding of strains within all species examined. As it is possible that multiple receptors presented on the target cells may overcome the reduced binding affinity of mutated receptors, we examined strain Rd binding to I91A and Q89A/N-substituted receptors expressed in transiently transfected COS cells. Whilst the latter receptors were targeted on cells with low levels of receptor expression, only a proportion (c. 50%) of cells with very high levels of I91A receptors had significant numbers of bacteria attached. Thus point mutations of CEACAMs can both decrease and increase bacterial load and additional factors that dictate bacterial binding include receptor levels on the target cells.