Effect of diphtheria toxin on protein synthesis: inactivation of one of the transfer factors.

The committee hailed this publication as the first report of the precise molecular function of a bacterial protein virulence factor. This study most certainly served as an inspiration to a number of scientists working on the modes of action of other bacterial toxins such as cholera toxin and Pseudomonas exotoxin A, and it heralded the beginning of the field of molecular and biochemical analysis of bacterial pathogenic components. In this publication, Collier clearly demonstrated that diphtheria toxin, which was already known to inhibit protein synthesis in cell-free systems, could, in the presence of the cofactor nicotinamide adenine dinucleotide (NAD), inactivate one of the supernatant factors required for the transfer of amino acids from aminoacyl-sRNA (now called tRNA) to ribosomes. He accomplished this remarkable biochemical feat by hypothesizing that diphtheria toxin must irreversibly inactivate one of the macromolecular components involved in protein synthesis and then systematically testing the effect of toxin on ribosomes, aminoacyl-sRNA, and the transfer factors. He designated as “factor II” the component that was inactivated; it is now called elongation factor 2 (EF-2). The understanding of how bacterial toxins act on eucaryotic cells has not only furthered the study of bacterial pathogenesis but has also led to the use of these substances as tools to dissect the biology of eucaryotic cells at the molecular level. ALISON O’BRIEN