Degradation of the Invasive Adenylate Cyclase Toxin of Bordetella Pertussis by the Eukaryotic Target Cell-Lysate

Abstract

Bordetella pertussis, the causative agent of whooping cough, produces several factors which have been suggested to play a role in the pathogenesis of the disease. One of these is an adenylate cyclase (AC) which has several unique properties. The location of the enzyme in the bacterium is largely extracytoplasmic and a small amount of it is secreted into the culture medium during exponential growth (Hewlett etal., 1976). It is activated up to 1000-fold by the Ca²⁺ -binding protein calmodulin (CaM) (Hewlett etal., 1976; Wolff etal., 1980) which does not exist in the bacteria. Confer and Eaton (1982) and Hanski and Farfel (1985) have shown that B. pertussis AC can penetrate various eukaryotic cells and generates high levels of intracellular cAMP. In Immune effector cells the increase of cAMP impairs functions such as chemotaxis, phagocytosis, superoxide generation and microbial killing, leading to evasion of host defences (Weiss and Hewlett, 1986). It was, therefore, suggested that B. pertussis AC acts as a toxin which suppresses immune responses and assists the survival of the bacterium (Weiss and Hewlett, 1986). The importance of B. pertussis AC as a virulence factor was demonstrated by using mutants deficient in AC which were avirulent (Weiss etal., 1984).