A wide range of bacterial adhesins are involved in targeting the CEACAM N-terminal domains and includes Opa proteins, a major adhesin family of pathogenic Neisseria and P5 proteins of Hi (Chen and Gotschlich, 1996; Virji et al., 1996a; Hill et al., 2001) . Nm and N. gonorrhoeae contain multiple copies of Opa genes that encode conserved domains which form b-barrel structures in bacterial membranes and variable domains that form surface exposed loops. In spite of the surface diversity afforded by the hyper-variable domains of the loops, the majority of the Opa proteins are capable of targeting CEACAMs (Virji et al., 1996a; Hauck and Meyer, 2003) . The P5 proteins of Hi are similar b-barrel forming proteins, also with surface variable loops (Webb and Cripps, 1998; Vandeputte-Rutten et al., 2003) . The interactions between these bacterial ligands and CEACAMs are complex and the binding domain appears to involve more than one variable loop of the bacterial adhesins (Virji et al., 1999; Bos et al., 2002; de Jonge et al., 2003) . Interestingly, antibody inhibition studies have shown that the diverse ligands of neisseria and haemophilus bind to an overlapping site on the N-domain. In addition, mutational analysis of the N-domain of CEACAM1 has identified several critical residues particularly Ile-91. Alanine substitutions at these sites abrogated binding of most Opa-and P5-expressing bacteria to CEACAM1. Additional residues such as Tyr-34, Ser-32, Val-39, Gln-44 and Gln-89, most of which located in the vicinity of Ile-91, appear to determine the efficiency of interactions of various Opa and P5 molecules (Virji et al., 1999; . The bacterial binding surface on the CEACAM1 N-domain is the protein face composed of the beta strands C′′, C′, C, F and G (CFG for brevity). Despite the extensive investigations in a number of laboratories particularly on neisserial Opa proteins, it remains unclear as to precisely how CEACAM-binding ligands engage with the receptors.