Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae

Haemophilus influenzae (Hi), a commensal of the human respiratory mucosa, i s an important cause of localized and systemic infections. We show that dis tinct strains belonging to typable (THi) and nontypable (NTHi) H, influenza e target human carcinoembryonic antigens (the membrane associated CEA famil y of:ell adhesion molecules, are now termed CEACAMs), All strains of H. inf luenzae biogroup aegyptius (Hi-aeg) and more than 70% of THi and NTHi strai ns tested specifically recognize CEACAMI-Fc soluble constructs. Furthermore , transfection of Chinese hamster ovary cells with human CEACAM1 cDNA alone was sufficient for promoting Hi interactions with the transfected cells, T he majority of the Hi-aeg strains tested interacted with soluble constructs containing only the N-terminal domain. In contrast, several THi and NTHi s trains reacted with soluble constructs only when additional extracellular A and B domains of the receptor were present. The use of monoclonal antibodi es confirmed that THi and NTHi strains also interact primarily at the N-dom ain, We used site-directed mutants of CEACAM1 that contained substitutions at surface exposed amino acids and a molecular model of the N-domain to ide ntify the residues involved in interactions with Hi ligands, The studies sh ow that a common region exposed at the CFG face of the molecule is targeted by diverse Hi strains. However, mutation at distinct sites within this are a affected the interactions of distinct strains signifying the potential fo r tissue tropism via this receptor. Analyses of the molecular basis of inte raction with human cell lines and purified CEA show that Hi strains, especi ally those belonging to Hi-aeg, interact with multiple CEACAMs, Because Nei sseria meningitidis (Nm) strains are also known to bind at the CFG face of the receptor, we used Nm and Hi strains in co-infection experiments and dem onstrate competition between these mucosal pathogens in colonization of tar get cells via CEACAMs.