title: Adhesion of Bordetella pertussis to eukaryotic cells requires a time-dependent export and maturation of filamentous hemagglutinin.
abstract: Bordetella pertussis, the human pathogen of whooping cough, when grown at 22 degrees C is nonvirulent and unable to bind eukaryotic cells. In response to a temperature shift to 37 degrees C, the bacterium acquires the ability to bind eukaryotic cells in a time-dependent fashion. By studying in vitro the temperature-induced transition, from the nonvirulent to the virulent state, we found that binding to CHO cells is mediated by the Arg-Gly-Asp-containing domain of filamentous hemagglutinin (FHA), a protein with multiple binding specificities. This protein is synthesized as a 367-kDa polypeptide within 10 min after temperature shift, but requires 2 hr before it is detected on the bacterial cell surface and starts to bind CHO cells. Mutations affecting the cell surface export of FHA abolish bacterial adhesion to CHO cells, while mutations in the outer membrane protein pertactin strongly reduce binding. This suggests that multiple chaperon proteins are required for a correct function of FHA. Finally, several hours after maximum binding efficiency is achieved, the N-terminal 220-kDa portion of FHA that contains the binding regions is cleaved off, possibly to release the bacteria from the bound cells and facilitate spreading. The different forms of FHA may play different roles during bacterial infection.
authors.affiliation: Immunobiological Research Institute Siena, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Aricò
authors.forename: S
authors.initials: S
authors.lastname: Nuti
authors.forename: V
authors.initials: V
authors.lastname: Scarlato
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001886:Bordetella pertussis / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006367:HeLa Cells; D006388:Hemagglutinins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis / Q000302:isolation & purification; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D006388:Hemagglutinins; D009842:Oligopeptides; D011498:Protein Precursors; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; C068929:pertactin; C047981:arginyl-glycyl-aspartic acid