“Bacterial Toxins” Section in the Journal Toxins: A Fantastic Multidisciplinary Interplay between Bacterial Pathogenicity Mechanisms, Physiological Processes, Genomic Evolution, and Subsequent Development of Identification Methods, Efficient Treatment, and Prevention of Toxigenic Bacteria

Toxins are powerful pathogenicity factors produced by certain bacteria, fungi, animals, and plants which mediate drastic interactions of these pathogens on the organism host[...].

unravel physiological processes. An emblematic example is that of Clostridium botulinum C3 exoenzyme, which was characterized as an ADP-ribosyltransferase of a novel G-protein of unknown function, termed Rho, from the Ras superfamily. C3 exoenzyme was found to break the actin filaments in cultured epithelial cells and this opened the door to understanding the regulation of actin filament polymerization via the small GTPases of the Rho family [5]. Therefore, bacterial toxins are at the frontier of various disciplines including bacteriology, cellular biology, molecular biology, structural biology, biochemistry, genetics, immunology, and vaccinology. The diverse properties of bacterial toxins are well documented, notably in the multidisciplinary special issues of the journal Toxins.
More recently, novel advances have been performed in bacterial toxins which have been mainly facilitated by the development/improvement of molecular technologies. Indeed, whole genome sequencing of saprophytic and pathogenic bacteria with subsequent genomics analysis allowed the identification of novel toxins and the exploration of their spreading and evolution in the bacterial world. For example, typhoid toxin was initially suspected in cells invaded by Salmonella typhi and was subsequently characterized by genomic analysis and crystal structure, which revealed a novel toxin organization consisting of two distinct enzymatic subunits and five binding subunits. Typhoid toxin seems to have evolved from assembly of several ancestor toxin genes spread in other bacteria, such as cytolethal distending toxins and pertussis toxin [6]. The rapidly increasing progress in the whole genome sequencing of microorganisms would probably result in identification of novel toxins and in-depth understanding of their evolution. Moreover, refinement of the crystal structure investigations allowed unravelling the 3D structure of large or complex toxins, such as the whole structure of the large clostridial glucosylating toxin A from Clostridium difficile [7] or botulinum progenitor toxin complex [8]. However, many aspects of these multifunctional toxin proteins remain to be discovered. Albeit cellular receptors have been identified for some toxins, they are largely unknown for many others. Strategic features, such as toxin dissemination into the host to target cells, interaction with the cell membrane, crossing the phospholipid bilayer, intracellular trafficking, and precise mechanisms of cell alteration are still under investigation for many toxins.
In addition to their interest in fundamental science, bacterial toxins are key players in various applied developments, including tools for diagnosis, prevention, and therapy of diseases, due to toxigenic bacteria. Indeed, the diagnosis of several diseases is based on the detection and identification of toxins in biological and/or environmental samples, such as foods. The development of sensitive and rapid in vitro methods of toxin characterization are still in progress using new or improved technologies, such as mass spectrometry, refined ELISA, or fluorescent techniques. Since the pioneering historical works, detoxified toxins (anatoxins) were shown to elicit a solid preventive response against diseases due to toxigenic bacteria. Anatoxins are among the most efficient vaccines against bacterial diseases. Recombinant toxin subunits, which are biologically inactive, but retain the immunogenicity, offer the advantage to be safer than the classical detoxified toxins. Development of efficient toxin inhibitors are of major importance (see the special issue of Toxins edited by H. Barth). Although bacterial toxins are very poisonous compounds, some of their properties have powerful therapeutic applications. The most representative example is that of botulinum toxins which are used for their anti-cholinergic effects. Thereby, the most potent toxins are the drugs which have the most numerous medical indications from the treatment of dystonia, strabismus, hypersecretory activity of cholinergic glands, urinary bladder dysfunction, pain, cosmetology, etc. Botulinum toxins are mainly used as wild-type purified proteins, but engineering of these molecules is in progress to exploit specific properties of these toxins, such as therapeutic effects on sensitive neurons and the treatment of pain [9]. Recombinant toxins have also been engineered to specifically kill malignant cells (immunotoxins), or to transport therapeutic compounds into specific host compartments hardly accessible by routine administration pathways, such as the central nervous system. In addition, toxin development concerns not only medical applications, but also broad technical innovations. Thereby, the specific pore-forming activity of Staphylococcus aureus alpha toxin is used in novel processes of DNA sequencing [10].
Bacterial toxins are an increasing field of interest for scientists, health professionals, teachers, and students from various disciplines. The journal Toxins, which gathers toxin articles in specific sections and special issues, is quite appropriate to receive high-quality manuscripts, reviews, editorials, comments, and to promote fruitful discussions in the scientific community. We hope that Toxins will be more and more attractive to receive original and pertinent submissions.

Conflicts of Interest:
The author declares no conflict of interest.