SULFATED GLYCOCONJUGATE RECEPTORS FOR THE BORDETELLA-PERTUSSIS ADHESIN FILAMENTOUS HEMAGGLUTININ (FHA) AND MAPPING OF THE HEPARIN-BINDING DOMAIN ON FHA

Filamentous hemagglutinin (FHA) is a major adhesin present on the surf ace of the gram-negative respiratory pathogen Bordetella pertussis. A number of binding mechanisms have been described for the interaction o f FHA with eukaryotic cells. We have focused on its function as a sulf ated polysaccharide-binding protein and on identifying potential recep tors for FHA on the epithelial cell surface. Using a thin-layer overla y technique, we found that FHA binds specifically to sulfated glycolip ids but not to gangliosides or other neutral glycolipids. These result s suggest that epithelial cell surface sulfated glycolipids function a s receptors for FHA. Further studies demonstrated that a Chinese hamst er ovary (CHO) cell strain deficient in glycosaminoglycan expression e xhibits greatly diminished attachment to FHA. By FRA-Affi-Gel chromato graphy, a putative receptor for FHA that has characteristics consisten t with a heparan sulfate proteoglycan was isolated from epithelial cel l extracts. In addition, by using recombinant FHA fusion proteins, a s pecific glycosaminoglycan-binding domain located near the N terminus o f the FHA molecule was identified. Our results indicate that the B. pe rtussis adhesin FHA may utilize sulfated glycolipids and proteoglycans commonly found on the surface of human cells and tissues to initiate infection.