Special Issue "Novel Properties of Well-Characterized Toxins"

Guest Editor
Prof. Dr. Vernon L. Tesh
Department of Microbial and Molecular Pathogenesis, Medical Research and Education Building, Room 3002, College of Medicine, Texas A&M University System Health Science Center, 8447 State Highway 47, Bryan, TX 77843-1114, USA
Website: http://medicine.tamhsc.edu/basic-sciences/mmp/faculty/vernon-tesh.html
E-Mail:
Phone: +1 979 436 0357
Fax: +1 979 845 3479
Interests: Shiga toxins; verotoxins; ribosome-inactivating proteins; intracellular signaling pathways activated by microbial toxins; ER stress response; regulation of cytokine expression; innate immune response to microbial toxins; microbial pathogenesis

Dear Colleagues,

Compounds expressed by microbes and plants originally described to possess toxic activities (e.g., cytotoxins, neurotoxins, enterotoxins, etc.) have proven to be remarkably multifunctional molecules. For example, the capacity of Shiga toxins, a family of cytotoxins expressed by enteric pathogens, to act as ribosome-inactivating proteins was characterized in the 1980’s. Yet, it has recently been shown that in addition to protein synthesis inhibition, Shiga toxins are capable of: i) mediating membrane curvature and invagination; ii) triggering protein kinase signaling cascades upon membrane receptor binding; iii) being routed to multiple intracellular compartments including lysosomes, the endoplasmic reticulum, and nuclear membranes; iv) mediating transcytotic transport across polarized epithelial monolayers without cytotoxicity; v) activating the ribotoxic stress response leading to MAPK activation; vi) activating the ER stress pathway leading to induction of transcription factors and chaperone expression; vii) inducing chemokine expression by human intestinal epithelial cells; viii) inducing cytokine expression by macrophages; ix) altering normal cell cycling; x) altering cytoskeletal elements; and xi) inducing apoptosis in some cell types and inhibiting spontaneous apoptosis in other cells. Thus, these “toxins” activate a myriad of biological processes, many of which may contribute to pathogenesis. The ability to genetically manipulate toxin genes to produce toxoids (mutations that attenuate toxicity) has revealed many heretofore uncharacterized biological properties of toxins. In this special issue of Toxins, we will explore recently described novel properties of well-characterized toxins, discuss their role in pathogenesis, and review potential clinical applications to prevent or ameliorate toxin-mediated disease.

Prof. Dr. Vernon L. Tesh
Guest Editor

Submission

All manuscripts should be submitted to toxins@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

• microbial toxins
• plant toxins
• biological functions of toxins
• non-toxic properties of toxins
• cellular response to toxins
• pathogenesis

Type of Paper: Review
Title: Modulation of Epithelial Integrity by Ribotoxic Insults: Mechanistic Implications of Environmentally-Linked Inflammatory Mucosal Diseases
Author: Yuseok Moon
Affiliation: Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan 626-813, Korea; E-Mail: moon@pnu.edu
Abstract: Specific ribosome-directed xenobiotics have the capacity to damage 28S ribosomal RNA by interfering with its functioning during gene translation. This can lead to what has been called ribotoxic stress responses that are closely associated with various disease processes in human and the domestic animals. Ribotoxic stress-associated pathogenesis is the integrated process by interactions among genes important in cellular homeostasis as well as a variety of cytopathogenic events including cell survival, proliferation, and stress responses. Since the primary toxic actions of most ribotoxic stress agents are generally recognized to be the functional inhibition of global protein synthesis, highly dividing tissues such as lymphoid tissue and epithelium are the most susceptible targets of toxic insult. In the present study, responses in the mucosal barrier by acute and chronic exposure to ribosome-inactivating agents were reviewed in various experimental models. The review was aimed at characterizing the mechanistic evidences of the ribotoxic stress responses and their implication as critical etiological factors of mucosa-associated diseases, particularly, epithelial inflammatory disease and carcinogenesis.

Type of paper: Review
Title: G Protein-Dependent and -Independent Actions of Pertussis Toxin
Authors: Supachoke Mangmool ¹ and Hitoshi Kurose ²
Affiliations: ¹Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Thailand, ² Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan; E-Mail: kurose@phar.kyushu-u.ac.jp;
Abstract: Pertussis toxin (PTX) is recognized as a specific tool that uncouples receptors from heterotrimeric G_i and G_o proteins (G_i/G_o) by ADP-ribosylation of G_i/G_o.  PTX is one of A-B toxins that are composed of A-protomer and B-oligomer.  A-protomer has ADP-ribosyltransferase activity on the a subunit of (Ga_i) leading to inhibition of receptor-G protein coupling.  On the other hand, B-oligomer recognizes and binds carbohydrate-containing receptors that deliver A-protomer into the cytosol.  It has been assumed that the effects of PTX are explained only by Ga_i/Ga_o modification.  However, Ga_i/Ga_o modification-independent effects of PTX have also been reported.  PTX binds to Toll-like receptor 4 and stimulates reactive oxygen species through activation of Rac.  The production of reactive oxygen species leads to activation of a transcription factor NF-kB.  In this review, we summarize that PTX binds at least to two receptors: one is responsible for Ga_i/Ga_o modification, and another is newly identified receptor that leads to activation of Rac and NF-kB.  As PTX induces cellular responses that are independent of Ga_i/Ga_o modification, it is essential to differentiate the responses by PTX through two receptors in future.
Keywords: Pertusis toxin, G_i protein, Toll-like receptor 4, NF-kB

Titile: The Interactions of Human Neutrophils with Shiga Toxins and Related Plant Toxins: Danger or Safety?
Author: Maurizio Brigotti
Affiliation: Dipartimento di Patologia Sperimentale, Università di Bologna, Via San Giacomo 14, 40126 Bologna, Italy; E-Mail: maurizio.brigotti@unibo.it; Tel.: +39-051-2094716; Fax: +39-051-2094746
Abstract: Shiga toxins and ricin are well characterized homologous toxins belonging to quite different biological kingdoms. Plant and bacteria have parallelly evolved the ability to produce these powerful toxins, while humans have evolved a defense system which recognizes molecular patterns common to foreign molecules through specific receptors expressed on the surface of the main actors of innate immunity, namely monocytes and neutrophils. The interactions between these toxins and neutrophils have been widely described and stimulated intense debates. The paper was aimed at reviewing this topic, focusing particularly on implications in the pathogenesis and diagnosis of hemolytic uremic syndrome.
Keywords: Shiga toxins; ricin; ribosome-inactivating proteins; polymorphonuclear leukocytes; hemolytic uremic syndrome