The 220-kDa Bordetella pertussis filamentous hemagglutinin (FHA) is the major exported protein found in culture supernatants. The structural gene of FHA has a coding potential for a 367-kDa protein, and the mature form constitutes the N-terminal 60% of the 367-kDa precursor. The C-terminal domain of the precursor was found to be important for the high-level secretion of full-length FHA but not of truncated analogs ( Exported proteins in gram-negative microorganisms face the challenge of having to cross two distinct membranes, called the inner and outer membranes. In most cases, translocation through the inner membrane involves the signal peptide-dependent general secretion pathway (for a recent review, see reference 22). Important exceptions include the members of protein families related to the RTX hemolysins (31). Transport across the outer membrane often requires the concerted action of several accessory proteins that were thought to be specific for a given exported protein but that appear now to fall within distinct protein families.Successful interaction of bacterial pathogens with their hosts usually requires the production of several extracellular proteins that constitute important virulence factors. Therefore, pathogenic organisms represent interesting models for the study of protein export, especially across the outer membrane. Bordetella pertussis, the etiologic agent of whooping cough, produces several virulence factors that are located at the outer surface of the organism or released into the extracellular milieu. These factors include pertussis toxin, adenylate cyclase toxin, filamentous hemagglutinin (FHA), fimbriae, and probably other proteins that have yet to be identified. Accessory genes important for the biogenesis and export of several of these factors have been isolated and studied (6,14,30,32,33). Interestingly, in each case the accessory proteins were found to be members of protein families involved in export and biogenesis of macromolecules in other bacterial genera.Among the various protein export systems of B. pertussis, the FHA export machinery is particularly efficient, because FHA represents the major secreted protein in B. pertussis culture supernatants. This high efficiency is particularly interesting because of the large size of monomeric FHA polypeptides (220 kDa).FHA is a major adhesin produced by several Bordetella species. It expresses at least three different adherence activities (for a recent review, see reference 13). The region downstream of the FHA structural gene (fhaB) contains several open reading frames, of which the three most proximal are involved in the biogenesis of the fimbriae (14,32,33) and the most distal is involved in the biogenesis of FHA (32). The protein encoded by this latter gene, named fhaC, has significant sequence similarities with accessory proteins involved in the secretion of hemolysins of Serratia marcescens (20) and Proteus mirabilis (27). In addition, the N-terminal region of FHA has strong sequence similarities with the N-terminal domains of t...

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