Stealth and mimicry by deadly bacterial toxins

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) 2006-02, Vol.31 (2), p.123-133
• Main Authors: Yates, Susan P., Jørgensen, René, Andersen, Gregers R., Merrill, A. Rod
• Format: Article
• Language: English
• Subjects: ADP Ribose Transferases - chemistry; ADP Ribose Transferases - metabolism; ADP Ribose Transferases - pharmacology; Amino Acid Sequence; Bacteria; Bacterial Toxins - chemistry; Bacterial Toxins - metabolism; Bacterial Toxins - pharmacology; Binding Sites; Consensus Sequence; Corynebacterium diphtheriae; Diphtheria Toxin - chemistry; Diphtheria Toxin - metabolism; Diphtheria Toxin - pharmacology; Exotoxins - chemistry; Exotoxins - metabolism; Exotoxins - pharmacology; Histidine - analogs & derivatives; Histidine - chemistry; Models, Molecular; Molecular Mimicry; Molecular Sequence Data; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas aeruginosa Exotoxin A; Sequence Alignment; Virulence Factors - chemistry; Virulence Factors - metabolism; Virulence Factors - pharmacology
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2005.12.007

Diphtheria toxin and exotoxin A are well-characterized members of the ADP-ribosyltransferase toxin family that function as virulence factors in the pathogenic bacteria Corynebacterium diphtheriae and Pseudomonas aeruginosa. Recent high-resolution structural data of the Michaelis (enzyme–substrate) complex of the P. aeruginosa toxin with an NAD + analog and eukaryotic elongation factor 2 (eEF2) have provided insights into the mechanism of inactivation of protein synthesis caused by these protein factors. In addition, rigorous steady-state and stopped-flow kinetic analyses of the toxin-catalyzed reaction, in combination with inhibitor studies, have resulted in a quantum leap in our understanding of the mechanistic details of this deadly enzyme mechanism. It is now apparent that these toxins use stealth and molecular mimicry in unleashing their toxic strategy in the infected host eukaryotic cell.