Secretion of Pertussis Toxin from Bordetella pertussis

Abstract

Production and secretion of pertussis toxin (PT) is essential for the virulence of Bordetella pertussis. Due to the large oligomeric structure of PT, transport of the toxin across bacterial membrane barriers represents a significant hurdle that the bacteria must overcome in order to maintain pathogenicity. During the secretion process, PT undergoes a two-step transport process. The first step involves transport of the individual polypeptide chains of PT across the inner membrane utilizing a generalized secretion pathway, most likely the bacterial Sec system. The second step involves the use of a specialized apparatus to transport the toxin across the outer membrane of the bacterial cell. This apparatus, which has been termed the Ptl transporter and which is unique to the PT secretion pathway, is a member of the type IV family of bacterial transporters. Here, the current understanding of the PT secretion process is reviewed including a description of the Ptl proteins that assemble to form the transporter, the general structure of type IV transporters, the known similarities and differences between canonical type IV substrate transport and Ptl-mediated transport of PT, as well as the known sequence of events in the assembly and secretion of PT.

Keywords: pertussis toxin; toxin secretion; type IV secretion.

Figure 1

Genes encoding the Ptl transporter of B. pertussis (top) and the VirB transporter of A. tumefaciens (bottom). Arrows of the same color represent homologous genes [4].

Figure 2

Schematic drawing of the structure of a type IV transporter complex consisting of homologs of VirB3-VirB10. The drawing is adapted from Low et al. [19].

Figure 3

Schematic depiction of the secretion of PT from B. pertussis. Individual polypeptide chains are synthesized with a signal sequence (pS1–pS5). The individual chains are then transported across the inner membrane by a Ptl-independent pathway such as the Sec pathway and their signal sequences are cleaved. The S1 subunit and the subunits comprising the B oligomer (S2–S5) then assemble before the toxin is released from the bacterial cell.