title: Natural-host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C-terminal domain, but not the RGD motif, during infection.
abstract: Bacteria of the Bordetella genus cause respiratory tract infections. Both broad host range (e.g. Bordetella bronchiseptica) and human-adapted (e.g. Bordetella pertussis) strains produce a surface-exposed and secreted protein called filamentous haemagglutinin (FHA) that functions in adherence and immunomodulation. Previous studies using B. pertussis and cultured mammalian cells identified several FHA domains with potential roles in host cell interactions, including an Arg-Gly-Asp (RGD) triplet that was reported to bind integrins on epithelial cells and monocytes to activate host signalling pathways. We show here that, in contrast to our previous report, the fhaB genes of B. pertussis and B. bronchiseptica are functionally interchangeable, at least with regard to the various in vitro and in vivo assays investigated. This result is significant because it indicates that information obtained studying FHA using B. bronchiseptica and natural-host animal models should apply to B. pertussis FHA as well. We also show that the C-terminus of mature FHA, which we name the MCD, mediates adherence to epithelial and macrophage-like cells and is required for colonization of the rat respiratory tract and modulation of the inflammatory response in mouse lungs. We could not, however, detect a role for the RGD in any of these processes.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Julio
authors.forename: Carol S
authors.initials: CS
authors.lastname: Inatsuka
authors.forename: Joseph
authors.initials: J
authors.lastname: Mazar
authors.forename: Christine
authors.initials: C
authors.lastname: Dieterich
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Cotter
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D001885:Bordetella Infections / Q000276:immunology; D016950:Bordetella bronchiseptica / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000276:immunology* / Q000378:metabolism; D014917:Whooping Cough / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D009842:Oligopeptides; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; C047981:arginyl-glycyl-aspartic acid