The HMW1 adhesin of nontypeable Haemophilus influenzae recognizes sialylated glycoprotein receptors on cultured human epithelial cells.

Disease due to nontypeable Haemophilus influenzae begins with colonization of the upper respiratory tract mucosa. We recently reported that two surface-exposed high-molecular-weight proteins (HMW1 and HMW2) expressed by a prototypic strain of nontypeable H. influenzae mediate attachment to cultured epithelial cells. In the present study, we examined the nature of the epithelial cell receptor with which HMW1 interacts. Both proteinase K pretreatment and periodate oxidation of epithelial monolayers resulted in a marked decrease in HMW1-mediated binding, suggesting interaction with a glycoprotein structure. Treatment with peptide-N-glycosidase F produced a similar decrease in attachment and thereby provided further evidence for this conclusion. Desialylation of the epithelial cell surface also reduced binding, implying the presence of sialic acid in the receptor structure. Furthermore, lectins specific for terminal alpha 2-3-linked sialic acid were capable of inhibiting HMW1-mediated attachment. In summary, our results indicate that the HMW1 adhesin interacts with a glycoprotein receptor containing N-linked oligosaccharide chains with sialic acid in an alpha 2-3 configuration.