The History of Pertussis Toxin

Abstract

Besides the typical whooping cough syndrome, infection with Bordetella pertussis or immunization with whole-cell vaccines can result in a wide variety of physiological manifestations, including leukocytosis, hyper-insulinemia, and histamine sensitization, as well as protection against disease. Initially believed to be associated with different molecular entities, decades of research have provided the demonstration that these activities are all due to a single molecule today referred to as pertussis toxin. The three-dimensional structure and molecular mechanisms of pertussis toxin action, as well as its role in protective immunity have been uncovered in the last 50 years. In this article, we review the history of pertussis toxin, including the paradigm shift that occurred in the 1980s which established the pertussis toxin as a single molecule. We describe the role molecular biology played in the understanding of pertussis toxin action, its role as a molecular tool in cell biology and as a protective antigen in acellular pertussis vaccines and possibly new-generation vaccines, as well as potential therapeutical applications.

Keywords: ADP-ribosylation; G proteins; histamine sensitization; islet activation; leukocytosis; pertussis vaccines.

Figure 1

The structure of pertussis toxin. The S1 subunit is depicted in yellow, the B oligomer is in blue. (A) Side view showing PT with its S1 subunit on the top of the B oligomer. (B) Bottom view showing the B oligomer forming a triangle with 5 α-helices in the middle, surrounding a pore through which the C-terminal end of S1 protrudes. (C) Representation of the active side residues Arg-9, Glu-129 and His-35 of S1 in stick mode. (D) Representation of the receptor-binding residues Tyr-100, Ser-104, Arg-125 and Asn-105 or Lys-105 (for S2 or S3, respectively) in stick mode. The structures are drawn based on the data from [23].