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 77807, USA
Website: http://medicine.tamhsc.edu/basic-sciences/mmp/faculty/vernon-tesh.html
E-Mail: tesh@medicine.tamhsc.edu
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

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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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs) for well prepared manuscripts submitted before 1 July 2013. The APC for manuscripts submitted from 1 July 2013 onwards are 1000 CHF per accepted paper.

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

Type of Paper: Review
Title: Review of the Inhibition of Biological Activities of Food-Related Toxins by Natural Compounds: Mycotoxins, Botulinum Neurotoxins, Cholera toxins, Shiga Toxins, Stapylococcus Enterotoxins, and Ricin
Authors: Mendel Friedman, Carol E. Levin and Reuven Rasooly
Affiliation: Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture, Albany, California 94710, USA; E-Mail: Mendel.Friedman@ars.usda.gov; Phone: 510-559-5615
Abstract: There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules.  The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition of the biological (toxicological) activity by natural plant compounds and plant extracts of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin produced by fungi; cholera toxin produced by Vibrio cholerae bacteria, Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; and ricin produced by seeds of the castor plant Ricinus communis.  Reduction of biological activity was achieved by one or more of the following approaches: inhibition of release of the toxin into the environment, especially food; alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity, and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins.   Research needs are suggested that may further facilitate reducing the toxic burden of the diet.  Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating undesirable effects of natural toxins that may present in the diet.

Type of Paper: Article
Title: pH-Dependent Modulation of Translocation Determinants in Dermonecrotic G-Protein-Deamidating Toxins
Authors: Tana L. Repella, Mengfei Ho and Brenda A. Wilson
Affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA; E-Mail: mengho@life.illinois.edu
Abstract: Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocidatoxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic domain into the cytosol.

Type of Paper: Article
Title: Resistance Mechanisms to Toxin-Mediated Charcoal Rot Infection in Maturity Group III Soybean: Role of Seed Phenol, Lignin, Isoflavones, and Seed Coat Minerals in Charcoal Rot Resistance
Authors: Nacer Bellaloui ¹ and Alemu Mengistu ², L.H.S. Zobiole ³ and Hamed K. Abbas ⁴
Affiliations: ¹ Crop Genetics Research Unit, USDA-ARS, Stoneville, MS, USA;
E-Mail: Nacer.Bellaloui@ARS.USDA.GOV
² Crop Genetics Research Unit, USDA-ARS, Jackson, TN, USA
³ Crop Protection, R&D, Dow AgroSciences – Brazil, Cascavel, Paraná, Brazil
⁴ Biological Control of Pests Research Unit, USDA-ARS, Stoneville, MS, USA
Abstract: Charcoal rot is a disease caused by the fungus Macrophomina phaseolina (Tassi) Goid, and thought to infect the plants through roots by a toxin-mediated mechanism, resulting in yield loss and poor seed quality, especially under drought conditions. The mechanism by which this infection occurs is not yet understood. Although moderately resistant soybean germplasm is available, there are no commercial soybean cultivars that are completely resistant to charcoal rot disease. The objective of this research was to further investigate the role of phytochemical compounds that may be associated with the defense mechanism in soybean using susceptible (S) (DK 3964) and moderately resistant (MR) (AG 3905) soybean genotypes to charcoal rot. A two-year field experiment was conducted to evaluate the effects of charcoal rot on seed phenol, isoflavones, and seed coat lignin and minerals concentration by infesting the soil with charcoal rot (infested soil conditions, INF) or control (noninfested soil conditions, NINF).  Assessment of inoculation, disease, and rating for root and stem severity were also assessed.  The results showed that the moderately resistant genotype had higher concentrations of seed phenolics, total isoflavones, and seed coat lignin under infested and non-infested conditions and under irrigated or non-irrigated conditions compared to the susceptible genotype. The same general trend was found for seed coat Ca, P, Fe, Zn, B, and Cu concentrations in the moderately resistant genotype compared with the susceptible genotype. Our research demonstrated that differences between susceptible and moderately resistant genotypes for seed phytochemical components may be associated with resistance mechanisms and toxin-mediated infection resulting from charcoal rot disease.

Type of Paper: Article
Title: Short Toxin-Like Proteins Attack the Defense Line of Innate Immunity
Authors: Yitshak Tirosh, Dan Ofer and Michal Linial *
Affiliation: Department of Biological Chemistry, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; yitshak.tirosh@mail.huji.ac.il (Y.T.); ddofer@gmail.com (D.O); michall@cc.huji.ac.il (M.L)
Abstract: Searching mammalian proteomes for toxin-like proteins (coined TOLIPs) revealed number of overlooked candidates that secrete short proteins with abundance of cysteins throughout their sequences. Using bioinformatics and experimental methods, the function of some TOLIPs was inferred. We focused on cysteine-rich peptides that belong to the Ly6/uPAR superfamily. These proteins, called ANLPs, comprise a set of duplicated genes that resemble snake a-bungaratoxin. Despite the overall similarity of the structural fold among Ly6/uPAR proteins, they display a rich repertoire of functions including binding to receptors, alteration of cell signaling and adhesion. We reported on the cellular outcome of ANLP activity on the inflammatory response. We found that that many TOLIPs attack the first line of defense of the immune system. We postulated that TOLIPs function as an endogenous tuning mechanism for the innate immune system. Modulation of signaling by toxin-like proteins is adapted to cope with stressed conditions and exposure to pathogens.