The structure-function relationships of two bacterial ADP-ribosylating toxins, pertussis toxin and Escherichia coli heat-labile toxin, were studied using site-directed mutagenesis and photo-affinity labeling. In the case of pertussis toxin, the information generated from the mutagenesis studies was used to create recombinant holotoxins for evaluation of immunobiological and toxic effects. The studies may lead to the development of suitable acellular vaccine constituents for prevention of pertussis (whooping cough), and for enteric bacterial diseases mediated by cholera-like enterotoxins. Additional work involved studies of the relationship of the ADP-ribosyltransferase activity of pertussis toxin to another recently described cryptic activity of the toxin by using defined mutants. These studies are important to the evaluation of the suitability of the mutants as human vaccine candidates, and help clarify the structural bases for the various observed effects of pertussis toxin both in vitro and in vivo.
