Invasion of human respiratory epithelial cells by Bordetella pertussis: possible role for a filamentous hemagglutinin Arg-Gly-Asp sequence and alpha5beta1 integrin.
Bordetella pertussis, the agent of whooping cough, is capable of invading human respiratory epithelial cells. In this study, we investigated the mechanisms by which B. pertussis invades the human lung epithelial cell line A549 and normal human bronchial epithelial (NHBE) cells. In vitro adhesion and invasion assays using both cell types with a virulent B. pertussis strain and its isogenic mutants revealed profound defects in a mutant deficient in filamentous hemagglutinin (FHA) expression. In addition, a mutant in which an FHA Arg-Gly-Asp (RGD) site had been changed to Arg-Ala-Asp had significantly diminished invasiveness, although its adhesiveness was comparable to that of the parental strain. Furthermore, a synthetic RGD-containing hexapeptide inhibited invasion of both cell types by the virulent strain. These results demonstrate that an RGD sequence of FHA is involved in B. pertussis invasion of epithelial cells in vitro. Monoclonal antibodies directed against human alpha5beta1 integrin, but not other integrins, blocked invasion, indicating that this integrin is involved in B. pertussis invasion. Taken together, these findings suggest that B. pertussis FHA may promote invasion of human respiratory epithelial cells through the interaction of its RGD sequence with host cell alpha5beta1 integrin.
Ishibashi
Y
Y
Department of Immunobiology, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo 204-8588, Japan. yishibas@my-pharm.ac.jp
Relman
D A
DA
Nishikawa
A
A
D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001886:Bordetella pertussis / Q000276:immunology / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology*; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009154:Mutation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D017469:Receptors, Fibronectin / Q000276:immunology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000382:microbiology*; D014407:Tumor Cells, Cultured; D014774:Virulence; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D006388:Hemagglutinins; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; C047981:arginyl-glycyl-aspartic acid