Leading Opinions (Closed)

A topical collection in Toxins (ISSN 2072-6651).

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Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, St. Lucia, QLD, 4072, Australia
Interests: venom molecular evolution; protein structure prediction; protein-ligand interactions; molecular dynamics simulations; pharmacophore modeling; computational ligand docking

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Collection Editor
Pharmakology and Toxikology, Albertstrasse 25, University of Freiburg, 79104 Freiburg, Germany
Interests: bacterial toxins; GTPases; signal transduction; toxins and carcinogenesis

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Topical Collection Information

Dear Colleagues,

Toxins are the poisonous products of organisms, such as plants, animals, or a wide variety of microorganisms. They are small molecules, peptides, or proteins, respectively. Despite their chemical variety, all toxins are biological weapons that allow the producing organism to hunt for prey or to defend itself.

In this Topical Collection of Toxins we are presenting “Leading Opinions” in:

1. Animal venoms

Venomous animals produce their venom secretion in specialized cells. The venom is delivered to a target animal through evocation of a wound. Once inside the target animal the venom disrupts endophysiological or biochemical processes in order to facilitate feeding, defense, or competition.

2. Bacterial toxins

Pathogenic bacteria produce a cocktail of protein toxins, which support their survival in the host organism. The toxins trigger the behavior of eukaryotic cells by diverse, but mostly highly-specific, mechanisms. Reprogramming of host cells includes inhibition of the immune cells, as well as a weakening of the barrier function of epithelia.

The growing knowledge about cellular receptors, uptake mechanisms, and molecular action of bacterial toxins open new fields for inhibition of the bacterial weapons and, on the other hand, allows the targeted use of these highly efficient enzymes for cell biological and therapeutic applications.

3. Mycotoxins

Mycotoxins are small molecules corresponding to secondary metabolites produced by pathogenic molds that infect plants and crops. It is now clear that these toxins play a critical role during host colonization. Unfortunately, in addition to cause massive damages in crops, mycotoxins, due to their high stability and prevalence in the food chain, cause also collateral victims: animals and humans ingesting contaminated foods. To limit the economical and health impacts of mycotoxins, we need to better understand the role played by mycotoxins during plant infection, to perform comparative studies of the effects of mycotoxins in plants and animals and to identify mechanisms able to confer resistance to mycotoxin effects.

Advancement in the understanding of how toxins are administered and act, as well as how they can be targeted, is happening at fast pace and in a wide range of scientific disciplines. Leading scientists will be invited to present current developments and ideas to the “Leading Opinions” Topical Collection of Toxins.

Prof. Dr. Holger Scheib
Prof. Dr. Gudula Schmidt
Dr. Marc Maresca
Collection Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short 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 thoroughly refereed through a double-blind 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 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

2017

2165 KiB  
Review
Studies on the Presence of Mycotoxins in Biological Samples: An Overview
by Laura Escrivá, Guillermina Font, Lara Manyes and Houda Berrada
Toxins 2017, 9(8), 251; https://doi.org/10.3390/toxins9080251 - 18 Aug 2017
Cited by 109 | Viewed by 9953
Abstract
Mycotoxins are fungal secondary metabolites with bioaccumulation levels leading to their carry-over into animal fluids, organs, and tissues. As a consequence, mycotoxin determination in biological samples from humans and animals has been reported worldwide. Since most mycotoxins show toxic effects at low concentrations [...] Read more.
Mycotoxins are fungal secondary metabolites with bioaccumulation levels leading to their carry-over into animal fluids, organs, and tissues. As a consequence, mycotoxin determination in biological samples from humans and animals has been reported worldwide. Since most mycotoxins show toxic effects at low concentrations and considering the extremely low levels present in biological samples, the application of reliable detection methods is required. This review summarizes the information regarding the studies involving mycotoxin determination in biological samples over the last 10 years. Relevant data on extraction methodology, detection techniques, sample size, limits of detection, and quantitation are presented herein. Briefly, liquid-liquid extraction followed by LC-MS/MS determination was the most common technique. The most analyzed mycotoxin was ochratoxin A, followed by zearalenone and deoxynivalenol—including their metabolites, enniatins, fumonisins, aflatoxins, T-2 and HT-2 toxins. Moreover, the studies were classified by their purpose, mainly focused on the development of analytical methodologies, mycotoxin biomonitoring, and exposure assessment. The study of tissue distribution, bioaccumulation, carry-over, persistence and transference of mycotoxins, as well as, toxicokinetics and ADME (absorption, distribution, metabolism and excretion) were other proposed goals for biological sample analysis. Finally, an overview of risk assessment was discussed. Full article
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1449 KiB  
Review
Bacterial Toxins for Cancer Therapy
by Nour-Imene Zahaf and Gudula Schmidt
Toxins 2017, 9(8), 236; https://doi.org/10.3390/toxins9080236 - 28 Jul 2017
Cited by 67 | Viewed by 12930
Abstract
Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier [...] Read more.
Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier function of epithelia. In most cases, these toxins are extremely effective enzymes with high specificity towards their cellular substrates, which are often central signaling molecules. Moreover, they encompass the capacity to enter mammalian cells and to modify their substrates in the cytosol. A few molecules, at least of some toxins, are sufficient to change the cellular morphology and function of a cell or even kill a cell. Since many of those toxins are well studied concerning molecular mechanisms, cellular receptors, uptake routes, and structures, they are now widely used to analyze or to influence specific signaling pathways of mammalian cells. Here, we review the development of immunotoxins and targeted toxins for the treatment of a disease that is still hard to treat: cancer. Full article
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948 KiB  
Review
Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics
by Sophie Fraeyman, Siska Croubels, Mathias Devreese and Gunther Antonissen
Toxins 2017, 9(7), 228; https://doi.org/10.3390/toxins9070228 - 18 Jul 2017
Cited by 235 | Viewed by 12629
Abstract
Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria [...] Read more.
Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range), higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well. Full article
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463 KiB  
Review
Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?
by Silvia W. Gratz
Toxins 2017, 9(3), 85; https://doi.org/10.3390/toxins9030085 - 28 Feb 2017
Cited by 53 | Viewed by 9120
Abstract
Masked mycotoxins are plant metabolites of mycotoxins which co-contaminate common cereal crops. Since their discovery, the question has arisen if they contribute to toxicity either directly or indirectly through the release of the parent mycotoxins. Research in this field is rapidly emerging and [...] Read more.
Masked mycotoxins are plant metabolites of mycotoxins which co-contaminate common cereal crops. Since their discovery, the question has arisen if they contribute to toxicity either directly or indirectly through the release of the parent mycotoxins. Research in this field is rapidly emerging and the aim of this review is to summarize the latest knowledge on the fate of masked mycotoxins upon ingestion. Fusarium mycotoxins are the most prevalent masked mycotoxins and evidence is mounting that DON3Glc and possibly other masked trichothecenes are stable in conditions prevailing in the upper gut and are not absorbed intact. DON3Glc is also not toxic per se, but is hydrolyzed by colonic microbes and further metabolized to DOM-1 in some individuals. Masked zearalenone is rather more bio-reactive with some evidence on gastric and small intestinal hydrolysis as well as hydrolysis by intestinal epithelium and components of blood. Microbial hydrolysis of ZEN14Glc is almost instantaneous and further metabolism also occurs. Identification of zearalenone metabolites and their fate in the colon are still missing as is further clarification on whether or not masked zearalenone is hydrolyzed by mammalian cells. New masked mycotoxins continuously emerge and it is crucial that we gain detailed understanding of their individual metabolic fate in the body before we can assess synergistic effects and extrapolate the additive risk of all mycotoxins present in food. Full article
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1941 KiB  
Review
Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens
by Wageha A. Awad, Claudia Hess and Michael Hess
Toxins 2017, 9(2), 60; https://doi.org/10.3390/toxins9020060 - 10 Feb 2017
Cited by 302 | Viewed by 15761
Abstract
Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as [...] Read more.
Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can utilize tight junction proteins as receptors for attachment and subsequent internalization, while others modify or destroy the tight junction proteins by different pathways and thereby provide a gateway to the underlying tissue. This review aims to deliver an overview of the tight junction structures and function, and its role in enteric bacterial pathogenesis with a special focus on chickens. A main conclusion will be that the molecular mechanisms used by enteric pathogens to disrupt epithelial barrier function in chickens needs a much better understanding, explicitly highlighted for Campylobacter jejuni, Salmonella enterica and Clostridium perfringens. This is a requirement in order to assist in discovering new strategies to avoid damages of the intestinal barrier or to minimize consequences from infections. Full article
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381 KiB  
Review
The Status of Fusarium Mycotoxins in Sub-Saharan Africa: A Review of Emerging Trends and Post-Harvest Mitigation Strategies towards Food Control
by Cynthia Adaku Chilaka, Marthe De Boevre, Olusegun Oladimeji Atanda and Sarah De Saeger
Toxins 2017, 9(1), 19; https://doi.org/10.3390/toxins9010019 - 5 Jan 2017
Cited by 99 | Viewed by 10423
Abstract
Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of [...] Read more.
Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of mycotoxins produced by Fusarium. These arrays of toxins have been implicated as the causal agents of wide varieties of toxic health effects in humans and animals ranging from acute to chronic. Global surveillance of Fusarium mycotoxins has recorded significant progress in its control; however, little attention has been paid to Fusarium mycotoxins in sub-Saharan Africa, thus translating to limited occurrence data. In addition, legislative regulation is virtually non-existent. The emergence of modified Fusarium mycotoxins, which may contribute to additional toxic effects, worsens an already precarious situation. This review highlights the status of Fusarium mycotoxins in sub-Saharan Africa, the possible food processing mitigation strategies, as well as future perspectives. Full article
957 KiB  
Review
Forthcoming Challenges in Mycotoxins Toxicology Research for Safer Food—A Need for Multi-Omics Approach
by Luca Dellafiora and Chiara Dall’Asta
Toxins 2017, 9(1), 18; https://doi.org/10.3390/toxins9010018 - 4 Jan 2017
Cited by 51 | Viewed by 10895
Abstract
The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should [...] Read more.
The presence of mycotoxins in food represents a severe threat for public health and welfare, and poses relevant research challenges in the food toxicology field. Nowadays, food toxicologists have to provide answers to food-related toxicological issues, but at the same time they should provide the appropriate knowledge in background to effectively support the evidence-based decision-making in food safety. Therefore, keeping in mind that regulatory actions should be based on sound scientific findings, the present opinion addresses the main challenges in providing reliable data for supporting the risk assessment of foodborne mycotoxins. Full article
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