Studies presented here suggest some possible polymorphisms that can increase bacterial load. Several SNPs in CEACAMs have been identified and are listed in the NCBI SNP database and three have been identified in the N-domain of CEACAM1 including one at Gln-89. In this case, a Gln-89 to His substitution is observed. Such a residue difference occurs within the members of CEACAM family. For example, CEA contains H at position 89 (Fig. 2) . This is the only major difference between CC1 and CEA that could affect bacterial binding (Fig. 2) . As such, the mutation Q89H in CC1 would be expected to produce CEA-like binding pattern and could affect tropism of the bacteria as observed for CEA (Virji et al., 1999; de Jonge et al., 2003) . Further studies are required to assess whether other CEACAM polymorphisms, for example, substitutions such as Y34F and Q89N occur in human Molecular analysis of bacterial ligand-CEACAM1 interactions 341 populations and their frequencies in susceptible populations. SNP substitutions may also change the colonization profile of the nasopharynx, because in our competition studies we could demonstrate that increased binding afforded by Q89N to Hi-aeg isolate Ha3 increases the binding of Ha3 such that it out-competes Nm isolate C751OpaB in an in vitro competition assay for this receptor. The situation with the native receptor was the reverse. As shown in Figs 8 and 9, additional factors that affect bacterial binding to cell-expressed receptor include receptor density. Whilst certain residue substitutions, e.g. I91A, reduce functional affinity of bacterial interactions, high receptor densities increase such affinity. The final outcome must depend on the interplay between these two parameters. In recent studies, the role of receptor density on enhancement of bacterial attachment and invasion have been evaluated in detail (Bradley et al., 2005; Rowe et al., 2006) . It would be interesting to analyse bacterial invasion in cell lines expressing variant CEACAM1 carrying the above mutations by employing cell lines in which the receptor expression levels can be controlled, which are under development.