ADHESION OF BORDETELLA-PERTUSSIS TO EUKARYOTIC CELLS REQUIRES A TIME-DEPENDENT EXPORT AND MATURATION OF FILAMENTOUS HEMAGGLUTININ

Bordetella pertussis, the human pathogen of whooping cough, when grown at 22-degrees-C is nonvirulent and unable to bind eukaryotic cells. I n response to a temperature shift to 37-degrees-C, the bacterium acqui res the ability to bind eukaryotic cells in a time-dependent fashion. By studying in vitro the temperature-induced transition, from the nonv irulent to the virulent state, we found that binding to CHO cells is m ediated by the Arg-Gly-Asp-containing domain of filamentous hemaggluti nin (FHA), a protein with multiple binding specificities. This protein is synthesized as a 367-kDa polypeptide within 10 min after temperatu re shift, but requires 2 hr before it is detected on the bacterial cel l surface and starts to bind CHO cells. Mutations affecting the cell s urface export of FHA abolish bacterial adhesion to CHO cells, while mu tations in the outer membrane protein pertactin strongly reduce bindin g. This suggests that multiple chaperon proteins are required for a co rrect function of FHA. Finally, several hours after maximum binding ef ficiency is achieved, the N-terminal 220-kDa portion of FHA that conta ins the binding regions is cleaved off, possibly to release the bacter ia from the bound cells and facilitate spreading. The different forms of FHA may play different roles during bacterial infection.