ADP-ribosylation was then recognized to be shared by numerous other intracellularly-active toxins. Thereby, DT modifies the elongation factor-2 (EF-2) by ADP-ribosylation, leading to inhibition of cell protein synthesis and cell death. Then, diphtheria toxin (DT) was the first toxin that was characterized to exert a novel enzymatic activity intracellularly. Clostridium perfringens alpha toxin was the first bacterial toxin identified as developing an enzymatic activity consisting of phospholipase C activity at the cell membrane surface. In the last decades, a great effort has been done to unravel the mechanisms of action of these very active proteins able to induce so severe symptoms in higher organisms. Indeed, bacterial toxins show an extreme diversity regarding their size (from 15 to more than 2700 amino acids), mode of secretion (different bacterial secretion types), structure (mono, binary, ternary, or multiple complex proteins), membrane/intracellular receptor recognition, enzymatic activity, or specific mode of action such as pore-forming activity. Numerous works, publications, and meetings have been related to these fascinating toxin proteins which display multiple activities and functions such an example is the Sourcebook of Bacterial Protein Toxins or the diverse special issues of the journal Toxins. However, in contrast to exotoxins, the virulence factors are directly injected into the cell where the bacterium is attached by specific secretion types, such as the type III secretion system, and their activity is restricted to the attacked cell. Specific factors produced by invasive bacteria, and called virulence factors, are related to exotoxins and some of them share similar enzymatic activities to those of exotoxins. While endotoxins are membrane compounds of Gram-negative bacteria which elicit an inflammatory response in host, exotoxins are secreted proteins which act locally and at distance of the bacterial colonization site. Classically, bacterial toxins are divided into exotoxins and endotoxins. The “Bacterial Toxins” section of the journal Toxins is entirely devoted to this topic. Numerous studies and publications were dedicated to bacterial toxin characterization and deciphering of their mechanisms of action. Notably, bacterial toxins were the first compounds which were identified as responsible for severe bacterial diseases in man and animals. Toxins are powerful pathogenicity factors produced by certain bacteria, fungi, animals, and plants which mediate drastic interactions of these pathogens on the organism host.
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