title: The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor.
abstract: Haemophilus influenzae is a human-specific pathogen and a major source of morbidity worldwide. Infection with this organism begins with colonization of the nasopharynx, a process that probably depends on adherence to respiratory epithelium. The Hia autotransporter protein is the major adhesin ex-pressed by a subset of non-typeable H. influenzae strains and promotes high-level adherence to a variety of human epithelial cell lines. In the current study, we discovered that the Hia passenger domain contains two distinct binding pockets, including one at the C-terminal end and a second at the N-terminal end. Competition assays revealed that the two binding pockets interact with the same host cell receptor structure, although with differing affinities. Additional experiments demonstrated that both binding domains are required for full-level bacterial adherence. These observations are reminiscent of eukaryotic cell adhesion molecules and highlight the first example of a bacterial adhesin with two domains that participate in a bivalent interaction with identical host cell receptors. Such an interaction increases avidity, thus stabilizing bacterial adherence to the epithelial surface, despite physical forces such as coughing, sneezing and mucociliary clearance.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, Division of Infectious Diseases, St Louis Children's Hospital, 660 South Euclid Ave., Campus Box 8208, St Louis, MO 63110, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Laarmann
authors.forename: David
authors.initials: D
authors.lastname: Cutter
authors.forename: Twyla
authors.initials: T
authors.lastname: Juehne
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barenkamp
authors.forename: Joseph W
authors.initials: JW
authors.lastname: St Geme
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D002460:Cell Line; D003228:Conjunctiva / Q000166:cytology; D004847:Epithelial Cells / Q000382:microbiology; D006193:Haemophilus influenzae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D018829:Adhesins, Bacterial; C429644:Hia adhesin; D011956:Receptors, Cell Surface