title: Role of adhesin release for mucosal colonization by a bacterial pathogen.
abstract: Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract.
authors.affiliation: INSERM U447, Institut National de Sante et la Recherche Medical Institut de Biologie de Lille, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Coutte
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reveneau
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.forename: Brigitte
authors.initials: B
authors.lastname: Quatannens
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Francoise
authors.initials: F
authors.lastname: Jacob-Dubuisson
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000281:Administration, Intranasal; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins; D001885:Bordetella Infections / Q000382:microbiology*; D001886:Bordetella pertussis / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D002460:Cell Line; D005260:Female; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D006388:Hemagglutinins; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D037342:Pertussis Toxin; D012697:Serine Endopeptidases; C437318:SphB1 protein, Bordetella pertussis