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Toxins
Volume 12
Issue 6
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Toxins, Volume 12, Issue 6 (June 2020) – 76 articles

Cover Story (view full-size image): The venoms of Viperidae snakes are rich in proteins that strongly affect the haemostatic system. This study describes the isolation, purification, and characterisation of an interesting procoagulant serine protease from the venom of the most venomous viper in Europe, Vipera ammodytes ammodytes (nose-horned viper). The blood coagulation-promoting effect of VaaSP-VX, as the glycoprotein was named, is most likely based on the simultaneous activation of blood coagulation factors V and X, precursors of the prothrombinase complex. A unique proteolytic specificity along with the resistance to serpin inhibition endow VaaSP-VX with promising medical potential, for example, in treating patients with haemophilia. View this paper
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19 pages, 2782 KiB  
Article
Occurrence of Mycotoxins in Winter Rye Varieties Cultivated in Poland (2017–2019)
by Robert Kosicki, Magdalena Twarużek, Paweł Dopierała, Bartosz Rudzki and Jan Grajewski
Toxins 2020, 12(6), 423; https://doi.org/10.3390/toxins12060423 - 26 Jun 2020
Cited by 15 | Viewed by 3135
Abstract
Rye (Secale cereale L.) is one of the most important cereals and is used in both the food and feed industries. It is produced mainly in a belt extending from Russia through Poland to Germany. Despite the great economic importance of [...] Read more.
Rye (Secale cereale L.) is one of the most important cereals and is used in both the food and feed industries. It is produced mainly in a belt extending from Russia through Poland to Germany. Despite the great economic importance of this cereal, there is little research on rye contamination with mycotoxins. In this study, the occurrence of Fusarium mycotoxins (deoxynivalenol, nivalenol, 3-acetyl-deoxynivalenol, monoacetoxyscirpenol, diacetoxyscirpenol, T-2 toxin, HT-2 toxin, and zearalenone), as well as ochratoxin A, in 60 winter rye samples of four varieties (KWS Binntto, KWS Serafino, Dańkowskie Granat and Farm Saved Seed) cultivated in three consecutive growing seasons in five different regions of Poland was determined using liquid chromatography with tandem mass spectrometry and fluorescence detection. Deoxynivalenol, T-2 toxin, HT-2 toxin, and zearalenone had the highest occurrence in samples (90%, 63%, 57%, and 45% positive results, respectively). The mean concentrations of these analytes were 28.8 µg/kg (maximum 354.1 µg/kg), 0.98 µg/kg (maximum 6.63 µg/kg), 2.98 µg/kg (maximum 29.8 µg/kg), and 0.69 µg/kg (maximum 10.2 µg/kg), respectively. The mean concentrations for individual mycotoxins were highest in the 2016/2017 growing season. In the 2016/2017 growing season, at least two mycotoxins were detected in 95% of the samples, while in the 2018/2019 growing season, 70% of samples contained one or no mycotoxins. The frequencies of mycotoxin occurrence in different rye varieties were similar. Although a high frequency of mycotoxin occurrence was noted (especially deoxynivalenol), their concentrations were low, and none of the analyzed rye samples exceeded the maximum acceptable mycotoxin level set by the European Commission. Full article
(This article belongs to the Special Issue Occurrence and Risk Assessment of Mycotoxins)
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25 pages, 4197 KiB  
Review
Evaluating the Potential for Cross-Interactions of Antitoxins in Type II TA Systems
by Chih-Han Tu, Michelle Holt, Shengfeng Ruan and Christina Bourne
Toxins 2020, 12(6), 422; https://doi.org/10.3390/toxins12060422 - 26 Jun 2020
Cited by 10 | Viewed by 5812
Abstract
The diversity of Type-II toxin–antitoxin (TA) systems in bacterial genomes requires tightly controlled interaction specificity to ensure protection of the cell, and potentially to limit cross-talk between toxin–antitoxin pairs of the same family of TA systems. Further, there is a redundant use of [...] Read more.
The diversity of Type-II toxin–antitoxin (TA) systems in bacterial genomes requires tightly controlled interaction specificity to ensure protection of the cell, and potentially to limit cross-talk between toxin–antitoxin pairs of the same family of TA systems. Further, there is a redundant use of toxin folds for different cellular targets and complexation with different classes of antitoxins, increasing the apparent requirement for the insulation of interactions. The presence of Type II TA systems has remained enigmatic with respect to potential benefits imparted to the host cells. In some cases, they play clear roles in survival associated with unfavorable growth conditions. More generally, they can also serve as a “cure” against acquisition of highly similar TA systems such as those found on plasmids or invading genetic elements that frequently carry virulence and resistance genes. The latter model is predicated on the ability of these highly specific cognate antitoxin–toxin interactions to form cross-reactions between chromosomal antitoxins and invading toxins. This review summarizes advances in the Type II TA system models with an emphasis on antitoxin cross-reactivity, including with invading genetic elements and cases where toxin proteins share a common fold yet interact with different families of antitoxins. Full article
(This article belongs to the Special Issue Toxin-Antitoxin Systems in Pathogenic Bacteria)
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22 pages, 5556 KiB  
Article
Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs
by Hyeon-Ju Lee, Jung-Hyun Park, Se-Young Oh, Du-Hyong Cho, Suji Kim and Inho Jo
Toxins 2020, 12(6), 421; https://doi.org/10.3390/toxins12060421 - 25 Jun 2020
Cited by 12 | Viewed by 3350
Abstract
Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter [...] Read more.
Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter analysis using 5′-serially deleted human eNOS promoter revealed that the proximal region (−135 to +22) was responsible for ZEN-mediated reduction of the human eNOS promoter activity. This effect was reversed by mutation of two specificity protein 1 (Sp1) binding elements in the human eNOS promoter. A chromatin immunoprecipitation assay revealed that ZEN increased Sp1 binding to the bovine eNOS promoter region (−113 to −12), which is homologous to −135 to +22 of the human eNOS promoter region. We also found that ZEN promoted the binding of the pregnane X receptor (PXR) to Sp1 of the bovine eNOS, consequently decreasing eNOS expression. This reduction of eNOS could have contributed to the decreased acetylcholine-induced vessel relaxation upon ZEN treatment in our ex vivo study using mouse aortas. In conclusion, our data demonstrate that ZEN decreases eNOS expression by enhancing the binding of PXR-Sp1 to the eNOS promoter, thereby decreasing NO production and potentially causing vessel dysfunction. Full article
(This article belongs to the Special Issue Effects of Feedborne Mycotoxins on Animal Health)
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11 pages, 286 KiB  
Article
Gustatory Function and the Uremic Toxin, Phosphate, Are Modulators of the Risk of Vascular Calcification among Patients with Chronic Kidney Disease: A Pilot Study
by Shih-I Chen, Chin-Ling Chiang, Chia-Ter Chao, Chih-Kang Chiang and Jenq-Wen Huang
Toxins 2020, 12(6), 420; https://doi.org/10.3390/toxins12060420 - 25 Jun 2020
Cited by 9 | Viewed by 2299
Abstract
Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having [...] Read more.
Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function. Full article
(This article belongs to the Section Uremic Toxins)
12 pages, 2193 KiB  
Article
Type A Trichothecene Diacetoxyscirpenol-Induced Emesis Corresponds to Secretion of Peptide YY and Serotonin in Mink
by Qinghua Wu, Kamil Kuca, Eugenie Nepovimova and Wenda Wu
Toxins 2020, 12(6), 419; https://doi.org/10.3390/toxins12060419 - 25 Jun 2020
Cited by 10 | Viewed by 2914
Abstract
The trichothecene mycotoxins contaminate cereal grains and have been related to alimentary toxicosis resulted in emetic response. This family of mycotoxins comprises type A to D groups of toxic sesquiterpene chemicals. Diacetoxyscirpenol (DAS), one of the most toxic type A trichothecenes, is considered [...] Read more.
The trichothecene mycotoxins contaminate cereal grains and have been related to alimentary toxicosis resulted in emetic response. This family of mycotoxins comprises type A to D groups of toxic sesquiterpene chemicals. Diacetoxyscirpenol (DAS), one of the most toxic type A trichothecenes, is considered to be a potential risk for human and animal health by the European Food Safety Authority. Other type A trichothecenes, T-2 toxin and HT-2 toxin, as well as type B trichothecene deoxynivalenol (DON), have been previously demonstrated to induce emetic response in the mink, and this response has been associated with the plasma elevation of neurotransmitters peptide YY (PYY) and serotonin (5-hydroxytryptamine, 5-HT). However, it is found that not all the type A and type B trichothecenes have the capacity to induce PYY and 5-HT. It is necessary to identify the roles of these two emetogenic mediators on DAS-induced emesis. The goal of this study was to determine the emetic effect of DAS and relate this effect to PYY and 5-HT, using a mink bioassay. Briefly, minks were fasted one day before experiment and given DAS by intraperitoneally and orally dosing on the experiment day. Then, emetic episodes were calculated and blood collection was employed for PYY and 5-HT test. DAS elicited robust emetic responses that corresponded to upraised PYY and 5-HT. Blocking the neuropeptide Y2 receptor (NPY2R) diminished emesis induction by PYY and DAS. The serotonin 3 receptor (5-HT3R) inhibitor granisetron totally restrained the induction of emesis by serotonin and DAS. In conclusion, our findings demonstrate that PYY and 5-HT have critical roles in DAS-induced emetic response. Full article
(This article belongs to the Special Issue Mycotoxins and Their Metabolites Biochemistry, Molecular Biology and Toxicology)
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15 pages, 629 KiB  
Article
Analysis of Cry1Ah Toxin-Binding Reliability to Midgut Membrane Proteins of the Asian Corn Borer
by Sivaprasath Prabu, Muhammad Zeeshan Shabbir, Zhenying Wang and Kanglai He
Toxins 2020, 12(6), 418; https://doi.org/10.3390/toxins12060418 - 24 Jun 2020
Cited by 5 | Viewed by 2634
Abstract
Evolution of insect resistance to Bt toxins challenges the use of Cry toxins to control agricultural pests. In lepidopterans, Cry toxin affinity towards multiple midgut epithelial receptors has become a matter of dispute. Cry1Ah toxin-binding proteins were identified in the larval midgut of [...] Read more.
Evolution of insect resistance to Bt toxins challenges the use of Cry toxins to control agricultural pests. In lepidopterans, Cry toxin affinity towards multiple midgut epithelial receptors has become a matter of dispute. Cry1Ah toxin-binding proteins were identified in the larval midgut of susceptible (ACB-BtS) and resistant (ACB-AhR) strains of the Asian corn borer (ACB). A pull-down assay was performed using biotinylated Cry1Ah toxin, and the binding proteins were identified by employing liquid chromatography–tandem mass spectrometry (LC-MS/MS). This study aimed to find the binding consistency of the midgut epithelial protein to the Cry1Ah toxin. The binding proteins from different fractions of SDS-PAGE showed a different pattern. We observed an isoform of prophenoloxidase PPO1b (UniProt Acc No. A0A1Q1MKI0), which was found only in the ACB-AhR fractions. Prophenoloxidase (proPO) is an extraordinary defense molecule activated in insect species during pathogen invasion and the wound healing process. Importantly, this prophenoloxidase might have direct/indirect interaction with the Cry1Ah toxin. Our data also suggest that factors like techniques, enrichment of binding proteins in the sample and the reversible and irreversible nature of the brush border membrane vesicles (BBMVs) to Cry toxins could cause the inconsistency in the protein–protein interactions. Moreover, inside the larva midgut, the influence of the Cry toxins under physiological conditions might be different from the laboratory procedures. Full article
(This article belongs to the Section Bacterial Toxins)
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16 pages, 1323 KiB  
Review
Recent Advances on Macrocyclic Trichothecenes, Their Bioactivities and Biosynthetic Pathway
by Muzi Zhu, Youfei Cen, Wei Ye, Saini Li and Weimin Zhang
Toxins 2020, 12(6), 417; https://doi.org/10.3390/toxins12060417 - 23 Jun 2020
Cited by 31 | Viewed by 3716
Abstract
Macrocyclic trichothecenes are an important group of trichothecenes bearing a large ring. Despite the fact that many of trichothecenes are of concern in agriculture, food contamination, health care and building protection, the macrocyclic ones are becoming the research hotspot because of their diversity [...] Read more.
Macrocyclic trichothecenes are an important group of trichothecenes bearing a large ring. Despite the fact that many of trichothecenes are of concern in agriculture, food contamination, health care and building protection, the macrocyclic ones are becoming the research hotspot because of their diversity in structure and biologic activity. Several researchers have declared that macrocyclic trichothecenes have great potential to be developed as antitumor agents, due to the plenty of their compounds and bioactivities. In this review we summarize the newly discovered macrocyclic trichothecenes and their bioactivities over the last decade, as well as identifications of genes tri17 and tri18 involved in the trichothecene biosynthesis and putative biosynthetic pathway. According to the search results in database and phylogenetic trees generated in the review, the species of the genera Podostroma and Monosporascus would probably be great sources for producing macrocyclic trichothecenes. Moreover, we propose that the macrocyclic trichothecene roridin E could be formed via acylation or esterification of the long side chain linked with C-4 to the hydroxyl group at C-15, and vice versa. More assays and evidences are needed to support this hypothesis, which would promote the verification of the proposed pathway. Full article
(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)
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5 pages, 226 KiB  
Editorial
Mobilizing Toxins for Cancer Treatment: Historical Perspectives and Current Strategies
by Jessica Kopenhaver, Robert D. Carlson and Adam E. Snook
Toxins 2020, 12(6), 416; https://doi.org/10.3390/toxins12060416 - 23 Jun 2020
Cited by 1 | Viewed by 2390
Abstract
The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...] Full article
(This article belongs to the Special Issue Toxins and Cancer Therapy)
11 pages, 752 KiB  
Article
Biomonitoring of Enniatin B1 and Its Phase I Metabolites in Human Urine: First Large-Scale Study
by Yelko Rodríguez-Carrasco, Alfonso Narváez, Luana Izzo, Anna Gaspari, Giulia Graziani and Alberto Ritieni
Toxins 2020, 12(6), 415; https://doi.org/10.3390/toxins12060415 - 22 Jun 2020
Cited by 15 | Viewed by 3022
Abstract
Enniatins (Enns) are mycotoxins produced by Fusarium spp. which are a fungus widely spread throughout cereals and cereal-based products. Among all the identified enniatins, Enn B1 stands as one of the most prevalent analogues in cereals in Europe. Hence, the aim of this [...] Read more.
Enniatins (Enns) are mycotoxins produced by Fusarium spp. which are a fungus widely spread throughout cereals and cereal-based products. Among all the identified enniatins, Enn B1 stands as one of the most prevalent analogues in cereals in Europe. Hence, the aim of this study was to evaluate for the first time the presence of Enn B1 and its phase I metabolites in 300 human urine samples using an ultrahigh-performance liquid chromatography high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) methodology. Enn B1 was detected in 94.3% of samples ranging from 0.007 to 0.429 ng/mL (mean value: 0.065 ng/mL). In accordance with previous in vitro and in vivo analysis, hydroxylated metabolites (78.0% samples) and carbonylated metabolites (66.0% samples) were tentatively identified as the major products. Results from this biomonitoring study point to a frequent intake of Enn B1 in the studied population, suggesting that in-depth toxicological studies are needed in order to understand the potential effects in humans. Full article
(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)
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21 pages, 2151 KiB  
Article
Metabolic Traits of Bovine Shiga Toxin-Producing Escherichia coli (STEC) Strains with Different Colonization Properties
by Stefanie A. Barth, Michael Weber, Katharina Schaufler, Christian Berens, Lutz Geue and Christian Menge
Toxins 2020, 12(6), 414; https://doi.org/10.3390/toxins12060414 - 22 Jun 2020
Cited by 6 | Viewed by 3609
Abstract
Cattle harbor Shiga toxin-producing Escherichia coli (STEC) in their intestinal tract, thereby providing these microorganisms with an ecological niche, but without this colonization leading to any clinical signs. In a preceding study, genotypic characterization of bovine STEC isolates unveiled that their ability to [...] Read more.
Cattle harbor Shiga toxin-producing Escherichia coli (STEC) in their intestinal tract, thereby providing these microorganisms with an ecological niche, but without this colonization leading to any clinical signs. In a preceding study, genotypic characterization of bovine STEC isolates unveiled that their ability to colonize cattle persistently (STECper) or only sporadically (STECspo) is more closely associated with the overall composition of the accessory rather than the core genome. However, the colonization pattern could not be unequivocally linked to the possession of classical virulence genes. This study aimed at assessing, therefore, if the presence of certain phenotypic traits in the strains determines their colonization pattern and if these can be traced back to distinctive genetic features. STECspo strains produced significantly more biofilm than STECper when incubated at lower temperatures. Key substrates, the metabolism of which showed a significant association with colonization type, were glyoxylic acid and L-rhamnose, which were utilized by STECspo, but not or only by some STECper. Genomic sequences of the respective glc and rha operons contained mutations and frameshifts in uptake and/or regulatory genes, particularly in STECper. These findings suggest that STECspo conserved features leveraging survival in the environment, whereas the acquisition of a persistent colonization phenotype in the cattle reservoir was accompanied by the loss of metabolic properties and genomic mutations in the underlying genetic pathways. Full article
(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)
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13 pages, 969 KiB  
Article
Toxicokinetics of Hydrolyzed Fumonisin B1 after Single Oral or Intravenous Bolus to Broiler Chickens Fed a Control or a Fumonisins-Contaminated Diet
by Gunther Antonissen, Siegrid De Baere, Barbara Novak, Dian Schatzmayr, Danica den Hollander, Mathias Devreese and Siska Croubels
Toxins 2020, 12(6), 413; https://doi.org/10.3390/toxins12060413 - 21 Jun 2020
Cited by 13 | Viewed by 3122
Abstract
The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg [...] Read more.
The toxicokinetics (TK) of hydrolyzed fumonisin B1 (HFB1) were evaluated in 16 broiler chickens after being fed either a control or a fumonisins-contaminated diet (10.8 mg fumonisin B1, 3.3 mg B2 and 1.5 mg B3/kg feed) for two weeks, followed by a single oral (PO) or intravenous (IV) dose of 1.25 mg/kg bodyweight (BW) of HFB1. Fumonisin B1 (FB1), its partially hydrolyzed metabolites pHFB1a and pHFB1b, and fully hydrolyzed metabolite HFB1, were determined in chicken plasma using a validated ultra-performance liquid chromatography–tandem mass spectrometry method. None of the broiler chicken showed clinical symptoms of fumonisins (FBs) or HFB1 toxicity during the trial, nor was an aberration in body weight observed between the animals fed the FBs-contaminated diet and those fed the control diet. HFB1 was shown to follow a two-compartmental pharmacokinetic model with first order elimination in broiler chickens after IV administration. Toxicokinetic parameters of HFB1 demonstrated a total body clearance of 16.39 L/kg·h and an intercompartmental flow of 8.34 L/kg·h. Low levels of FB1 and traces of pHFB1b were found in plasma of chickens fed the FBs-contaminated diet. Due to plasma concentrations being under the limit of quantification (LOQ) after oral administration of HFB1, no toxicokinetic modelling could be performed in broiler chickens after oral administration of HFB1. Moreover, no phase II metabolites, nor N-acyl-metabolites of HFB1 could be detected in this study. Full article
(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)
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24 pages, 1955 KiB  
Review
How do Uremic Toxins Affect the Endothelium?
by Regiane Stafim da Cunha, Andressa Flores Santos, Fellype Carvalho Barreto and Andréa Emilia Marques Stinghen
Toxins 2020, 12(6), 412; https://doi.org/10.3390/toxins12060412 - 20 Jun 2020
Cited by 40 | Viewed by 7204
Abstract
Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, [...] Read more.
Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD. Full article
(This article belongs to the Special Issue Role of Uremic Toxins in Vascular Calcification, Vascular Disease and Bone Dysfunction)
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14 pages, 2109 KiB  
Article
Listeria monocytogenes Interferes with Host Cell Mitosis through Its Virulence Factors InlC and ActA
by Ana Catarina Costa, Jorge Pinheiro, Sandra A. Reis, Didier Cabanes and Sandra Sousa
Toxins 2020, 12(6), 411; https://doi.org/10.3390/toxins12060411 - 20 Jun 2020
Cited by 8 | Viewed by 4948
Abstract
Listeria monocytogenes is among the best-characterized intracellular pathogens. Its virulence factors, and the way they interfere with host cells to hijack host functions and promote the establishment and dissemination of the infection, have been the focus of multiple studies over the last 30 [...] Read more.
Listeria monocytogenes is among the best-characterized intracellular pathogens. Its virulence factors, and the way they interfere with host cells to hijack host functions and promote the establishment and dissemination of the infection, have been the focus of multiple studies over the last 30 years. During cellular infection, L. monocytogenes was shown to induce host DNA damage and delay the host cell cycle to its own benefit. However, whether the cell cycle stage would interfere with the capacity of Listeria to infect human cultured cell lines was never assessed. We found here that L. monocytogenes preferentially infects cultured cells in G2/M phases. Inside G2/M cells, the bacteria lead to an increase in the overall mitosis duration by delaying the mitotic exit. We showed that L. monocytogenes infection causes a sustained activation of the spindle assembly checkpoint, which we correlated with the increase in the percentage of misaligned chromosomes detected in infected cells. Moreover, we demonstrated that chromosome misalignment in Listeria-infected cells required the function of two Listeria virulence factors, ActA and InlC. Our findings show the pleiotropic role of Listeria virulence factors and their cooperative action in successfully establishing the cellular infection. Full article
(This article belongs to the Special Issue Toxins and Virulence Factors of Listeria monocytogenes)
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13 pages, 21155 KiB  
Review
Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety
by Bo Chen, Yanlei Sun, Feifei Luo and Chengshu Wang
Toxins 2020, 12(6), 410; https://doi.org/10.3390/toxins12060410 - 19 Jun 2020
Cited by 35 | Viewed by 9758
Abstract
Ascomycete Cordyceps fungi such as C. militaris, C. cicadae, and C. guangdongensis have been mass produced on artificial media either as food supplements or health additives while the byproducts of culture substrates are largely used as animal feed. The safety concerns [...] Read more.
Ascomycete Cordyceps fungi such as C. militaris, C. cicadae, and C. guangdongensis have been mass produced on artificial media either as food supplements or health additives while the byproducts of culture substrates are largely used as animal feed. The safety concerns associated with the daily consumption of Cordyceps fungi or related products are still being debated. On the one hand, the known compounds from these fungi such as adenosine analogs cordycepin and pentostatin have demonstrated different beneficial or pharmaceutical activities but also dose-dependent cytotoxicities, neurological toxicities and or toxicological effects in humans and animals. On the other hand, the possibility of mycotoxin production by Cordyceps fungi has not been completely ruled out. In contrast to a few metabolites identified, an array of biosynthetic gene clusters (BGCs) are encoded in each genome of these fungi with the potential to produce a plethora of as yet unknown secondary metabolites. Conservation analysis of BGCs suggests that mycotoxin analogs of PR-toxin and trichothecenes might be produced by Cordyceps fungi. Future elucidation of the compounds produced by these functionally unknown BGCs, and in-depth assessments of metabolite bioactivity and chemical safety, will not only facilitate the safe use of Cordyceps fungi as human food or alternative medicine, but will also benefit the use of mass production byproducts as animal feed. To corroborate the long record of use as a traditional medicine, future efforts will also benefit the exploration of Cordyceps fungi for pharmaceutical purposes. Full article
(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)
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12 pages, 1260 KiB  
Article
Reduced Membrane-Bound Alkaline Phosphatase Does Not Affect Binding of Vip3Aa in a Heliothis virescens Resistant Colony
by Daniel Pinos, Maissa Chakroun, Anabel Millán-Leiva, Juan Luis Jurat-Fuentes, Denis J. Wright, Patricia Hernández-Martínez and Juan Ferré
Toxins 2020, 12(6), 409; https://doi.org/10.3390/toxins12060409 - 19 Jun 2020
Cited by 15 | Viewed by 3892
Abstract
The Vip3Aa insecticidal protein from Bacillus thuringiensis (Bt) is produced by specific transgenic corn and cotton varieties for efficient control of target lepidopteran pests. The main threat to this technology is the evolution of resistance in targeted insect pests and understanding the mechanistic [...] Read more.
The Vip3Aa insecticidal protein from Bacillus thuringiensis (Bt) is produced by specific transgenic corn and cotton varieties for efficient control of target lepidopteran pests. The main threat to this technology is the evolution of resistance in targeted insect pests and understanding the mechanistic basis of resistance is crucial to deploy the most appropriate strategies for resistance management. In this work, we tested whether alteration of membrane receptors in the insect midgut might explain the >2000-fold Vip3Aa resistance phenotype in a laboratory-selected colony of Heliothis virescens (Vip-Sel). Binding of 125I-labeled Vip3Aa to brush border membrane vesicles (BBMV) from 3rd instar larvae from Vip-Sel was not significantly different from binding in the reference susceptible colony. Interestingly, BBMV from Vip-Sel larvae showed dramatically reduced levels of membrane-bound alkaline phosphatase (mALP) activity, which was further confirmed by a strong downregulation of the membrane-bound alkaline phosphatase 1 (HvmALP1) gene. However, the involvement of HvmALP1 as a receptor for the Vip3Aa protein was not supported by results from ligand blotting and viability assays with insect cells expressing HvmALP1. Full article
(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)
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20 pages, 981 KiB  
Review
Epidemiological and Clinical Evidence for the Role of Toxins in S. aureus Human Disease
by Monique R. Bennett and Isaac P. Thomsen
Toxins 2020, 12(6), 408; https://doi.org/10.3390/toxins12060408 - 19 Jun 2020
Cited by 22 | Viewed by 4897
Abstract
Staphylococcus aureus asymptomatically colonizes approximately 30–50% of the population and is a leading cause of bacteremia, bone/joint infections, and skin infections in the US. S. aureus has become a major public health threat due to antibiotic resistance and an increasing number of failed [...] Read more.
Staphylococcus aureus asymptomatically colonizes approximately 30–50% of the population and is a leading cause of bacteremia, bone/joint infections, and skin infections in the US. S. aureus has become a major public health threat due to antibiotic resistance and an increasing number of failed vaccine attempts. To develop new anti-staphylococcal preventive therapies, it will take a more thorough understanding of the current role S. aureus virulence factors play in contributing to human disease. This review focuses on the clinical association of individual toxins with S. aureus infection as well as attempted treatment options. Further understanding of these associations will increase understanding of toxins and their importance to S. aureus pathogenesis. Full article
(This article belongs to the Special Issue Immunotherapies and Vaccines against Diseases Caused by Staphylococcal Toxins)
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12 pages, 2658 KiB  
Article
The Southeast Alaska Tribal Ocean Research (SEATOR) Partnership: Addressing Data Gaps in Harmful Algal Bloom Monitoring and Shellfish Safety in Southeast Alaska
by John R. Harley, Kari Lanphier, Esther G. Kennedy, Tod A. Leighfield, Allison Bidlack, Matthew O. Gribble and Christopher Whitehead
Toxins 2020, 12(6), 407; https://doi.org/10.3390/toxins12060407 - 19 Jun 2020
Cited by 19 | Viewed by 4486
Abstract
Many communities in Southeast Alaska harvest shellfish such as mussels and clams as an important part of a subsistence or traditional diet. Harmful algal blooms (HABs) of phytoplankton such as Alexandrium spp. produce toxins that can accumulate in shellfish tissues to concentrations that [...] Read more.
Many communities in Southeast Alaska harvest shellfish such as mussels and clams as an important part of a subsistence or traditional diet. Harmful algal blooms (HABs) of phytoplankton such as Alexandrium spp. produce toxins that can accumulate in shellfish tissues to concentrations that can pose a hazard for human health. Since 2013, several tribal governments and communities have pooled resources to form the Southeast Alaska Tribal Ocean Research (SEATOR) network, with the goal of minimizing risks to seafood harvest and enhancing food security. SEATOR monitors toxin concentrations in shellfish and collects and consolidates data on environmental variables that may be important predictors of toxin levels such as sea surface temperature and salinity. Data from SEATOR are publicly available and are encouraged to be used for the development and testing of predictive algorithms that could improve seafood risk assessment in Southeast Alaska. To date, more than 1700 shellfish samples have been analyzed for paralytic shellfish toxins (PSTs) in more than 20 locations, with potentially lethal concentrations observed in blue mussels (Mytilus trossulus) and butter clams (Saxidomus gigantea). Concentrations of PSTs exhibit seasonality in some species, and observations of Alexandrium are correlated to sea surface temperature and salinity; however, concentrations above the threshold of concern have been found in all months, and substantial variation in concentrations of PSTs remain unexplained. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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12 pages, 2364 KiB  
Article
Algicidal Molecular Mechanism and Toxicological Degradation of Microcystis aeruginosa by White-Rot Fungi
by Guoming Zeng, Pei Gao, Jiale Wang, Jinxi Zhang, Maolan Zhang and Da Sun
Toxins 2020, 12(6), 406; https://doi.org/10.3390/toxins12060406 - 19 Jun 2020
Cited by 20 | Viewed by 3210
Abstract
Current research on the inhibition of Microcystis aeruginosa growth is primarily focused on algae-lysing bacteria, and few studies have investigated the inhibitory mechanisms by which fungi affect it at the molecular level. A comparative analysis of the effects of Phanerochaete chrysosporium on the [...] Read more.
Current research on the inhibition of Microcystis aeruginosa growth is primarily focused on algae-lysing bacteria, and few studies have investigated the inhibitory mechanisms by which fungi affect it at the molecular level. A comparative analysis of the effects of Phanerochaete chrysosporium on the expression of the algal cell antioxidant protease synthesis gene prx, the biological macromolecule damage and repair genes recA, grpE, and fabZ, and the photosynthesis system-related genes psaB, psbD1 and rbcL, as well as genes for algal toxin synthesis mcyB, were performed to elucidate the molecular mechanism of Phanerochaete chrysosporium against Microcystis aeruginosa cells. RT-qPCR technology was used to study the molecular mechanism of algal cell inhibition by Phanerochaete chrysosporium liquid containing metabolites of Phanerochaete chrysosporium, Phanerochaete chrysosporium supernatant and Phanerochaete chrysosporium inactivated via high temperature sterilization at the gene expression level. Compared with the control, the chlorophyll-a contents dropped, and the recA, grpE, fabZ, and prx increased, but the psaB, psbD1, rbcL and mcyB showed that they were significantly reduced, which indicated that Phanerochaete chrysosporium can not only effectively destroy algal cells, but they may also reduce the expression of the Microcystis aeruginosa toxin gene and significantly block the metabolic system underlying the growth of algal cells and the synthesis of microcystins. Full article
(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)
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18 pages, 2113 KiB  
Article
Evaluation of the Efficacy of Mycotoxin Modifiers and Mycotoxin Binders by Using an In Vitro Rumen Model as a First Screening Tool
by Sandra Debevere, Dian Schatzmayr, Nicole Reisinger, Markus Aleschko, Geert Haesaert, Michael Rychlik, Siska Croubels and Veerle Fievez
Toxins 2020, 12(6), 405; https://doi.org/10.3390/toxins12060405 - 19 Jun 2020
Cited by 13 | Viewed by 4421
Abstract
Ruminal microbiota of cattle are not able to detoxify all mycotoxins. In addition, detoxification can be hampered by adverse ruminal conditions (e.g., low ruminal pH). Hence, in the cattle husbandry, mycotoxin binders and modifiers could be used to prevent animal exposure to mycotoxins. [...] Read more.
Ruminal microbiota of cattle are not able to detoxify all mycotoxins. In addition, detoxification can be hampered by adverse ruminal conditions (e.g., low ruminal pH). Hence, in the cattle husbandry, mycotoxin binders and modifiers could be used to prevent animal exposure to mycotoxins. In this study, an in vitro rumen model, including feed matrix, was established as first screening tool to test the efficacy of five products claiming to detoxify mycotoxins. The detoxifiers had different modes of action: (a) binding (three products); (b) enzymatic detoxification of zearalenone (ZEN; one product, ZenA); and (c) bacterial transformation of trichothecenes (one product, BBSH 797). For the mycotoxin binders, the binding to the mycotoxins enniatin B (ENN B), roquefortine C (ROQ-C), mycophenolic acid (MPA), deoxynivalenol (DON), nivalenol (NIV), and zearalenone (ZEN) were tested at a dose recommended by the manufacturers. The in vitro model demonstrated that all binders adsorbed ENN B to a certain extent, while only one of the binders also partially adsorbed ROQ-C. The binders did not change the concentrations of the other mycotoxins in the ruminal fluid. The enzyme ZenA detoxified ZEN very quickly and prevented the formation of the more toxic metabolite α-zearalenol (α-ZEL), both at normal (6.8) and low ruminal pH (5.8). The addition of BBSH 797 enhanced detoxification of DON and NIV, both at normal and low ruminal pH. The in vitro rumen model demonstrated that the addition of ZenA seems to be a very promising strategy to prevent estrogenic effects of ZEN contaminated feed, and BBSH 797 is efficient in the detoxification of trichothecenes. Full article
(This article belongs to the Special Issue Removal and Control of Mycotoxins Contamination)
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27 pages, 960 KiB  
Review
Uremic Toxins and Vascular Dysfunction
by Isabelle Six, Nadia Flissi, Gaëlle Lenglet, Loïc Louvet, Said Kamel, Marlène Gallet, Ziad A. Massy and Sophie Liabeuf
Toxins 2020, 12(6), 404; https://doi.org/10.3390/toxins12060404 - 18 Jun 2020
Cited by 42 | Viewed by 5692
Abstract
Vascular dysfunction is an essential element found in many cardiovascular pathologies and in pathologies that have a cardiovascular impact such as chronic kidney disease (CKD). Alteration of vasomotricity is due to an imbalance between the production of relaxing and contracting factors. In addition [...] Read more.
Vascular dysfunction is an essential element found in many cardiovascular pathologies and in pathologies that have a cardiovascular impact such as chronic kidney disease (CKD). Alteration of vasomotricity is due to an imbalance between the production of relaxing and contracting factors. In addition to becoming a determining factor in pathophysiological alterations, vascular dysfunction constitutes the first step in the development of atherosclerosis plaques or vascular calcifications. In patients with CKD, alteration of vasomotricity tends to emerge as being a new, less conventional, risk factor. CKD is characterized by the accumulation of uremic toxins (UTs) such as phosphate, para-cresyl sulfate, indoxyl sulfate, and FGF23 and, consequently, the deleterious role of UTs on vascular dysfunction has been explored. This accumulation of UTs is associated with systemic alterations including inflammation, oxidative stress, and the decrease of nitric oxide production. The present review proposes to summarize our current knowledge of the mechanisms by which UTs induce vascular dysfunction. Full article
(This article belongs to the Special Issue Role of Uremic Toxins in Vascular Calcification, Vascular Disease and Bone Dysfunction)
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18 pages, 2456 KiB  
Article
The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity
by Neil Chernoff, Donna Hill, Johnsie Lang, Judy Schmid, Thao Le, Amy Farthing and Hwa Huang
Toxins 2020, 12(6), 403; https://doi.org/10.3390/toxins12060403 - 18 Jun 2020
Cited by 49 | Viewed by 4809
Abstract
Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR [...] Read more.
Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose–response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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18 pages, 3366 KiB  
Article
Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis
by John P. Dunbar, Antoine Fort, Damien Redureau, Ronan Sulpice, Michel M. Dugon and Loïc Quinton
Toxins 2020, 12(6), 402; https://doi.org/10.3390/toxins12060402 - 18 Jun 2020
Cited by 22 | Viewed by 14290
Abstract
The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it [...] Read more.
The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance. Full article
(This article belongs to the Special Issue Venom Proteomics and Transcriptomics)
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2 pages, 166 KiB  
Editorial
In Memoriam to Vittorio Ricci, Professor of Pathology at Pavia University
by Patrice Boquet
Toxins 2020, 12(6), 401; https://doi.org/10.3390/toxins12060401 - 17 Jun 2020
Viewed by 1901
Abstract
My great friend Vittorio Ricci died suddenly on 4 May 2020 [...] Full article
(This article belongs to the Section Bacterial Toxins)
18 pages, 1876 KiB  
Article
In Vitro Toxicological Screening of Stable and Senescing Cultures of Aphanizomenon, Planktothrix, and Raphidiopsis
by Łukasz Wejnerowski, Halina Falfushynska, Oksana Horyn, Inna Osypenko, Mikołaj Kokociński, Jussi Meriluoto, Tomasz Jurczak, Barbara Poniedziałek, Filip Pniewski and Piotr Rzymski
Toxins 2020, 12(6), 400; https://doi.org/10.3390/toxins12060400 - 17 Jun 2020
Cited by 7 | Viewed by 3314
Abstract
Toxicity of cyanobacteria is the subject of ongoing research, and a number of toxic metabolites have been described, their biosynthesis pathways have been elucidated, and the mechanism of their action has been established. However, several knowledge gaps still exist, e.g., some strains produce [...] Read more.
Toxicity of cyanobacteria is the subject of ongoing research, and a number of toxic metabolites have been described, their biosynthesis pathways have been elucidated, and the mechanism of their action has been established. However, several knowledge gaps still exist, e.g., some strains produce hitherto unknown toxic compounds, while the exact dynamics of exerted toxicity during cyanobacterial growth still requires further exploration. Therefore, the present study investigated the toxicity of extracts of nine freshwater strains of Aphanizomenon gracile, an Aphanizomenon sp. strain isolated from the Baltic Sea, a freshwater strain of Planktothrix agardhii, and two strains of Raphidiopsis raciborskii obtained from 25- and 70-day-old cultures. An in vitro experimental model based on Cyprinus carpio hepatocytes (oxidative stress markers, DNA fragmentation, and serine/threonine protein activity) and brain homogenate (cholinesterase activity) was employed. The studied extracts demonstrated toxicity to fish cells, and in general, all examined extracts altered at least one or more of considered parameters, indicating that they possess, to some degree, toxic potency. Although the time from which the extracts were obtained had a significant importance for the response of fish cells, we observed strong variability between the different strains and species. In some strains, extracts that originated from 25-day-old cultures triggered more harmful effects on fish cells compared to those obtained from 70-day-old cultures, whereas in other strains, we observed the opposite effect or a lack of a significant change. Our study revealed that there was no clear or common pattern regarding the degree of cyanobacterial bloom toxicity at a given stage of development. This means that young cyanobacterial blooms that are just forming can pose an equally toxic threat to aquatic vertebrates and ecosystem functioning as those that are stable or old with a tendency to collapse. This might be largely due to a high variability of strains in the bloom. Full article
(This article belongs to the Special Issue Human Exposure to Freshwater Toxins: Assessment, Potential, Consequences and Prevention)
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13 pages, 1879 KiB  
Article
In Vitro Assessment of Biocontrol Effects on Fusarium Head Blight and Deoxynivalenol (DON) Accumulation by DON-Degrading Bacteria
by Hiroyuki Morimura, Michihiro Ito, Shigenobu Yoshida, Motoo Koitabashi, Seiya Tsushima, Maurizio Camagna, Sotaro Chiba, Daigo Takemoto, Kazuhito Kawakita and Ikuo Sato
Toxins 2020, 12(6), 399; https://doi.org/10.3390/toxins12060399 - 16 Jun 2020
Cited by 24 | Viewed by 4811
Abstract
Fusarium head blight (FHB) of cereals is a severe disease caused by the Fusarium graminearum species complex. It leads to the accumulation of the mycotoxin deoxynivalenol (DON) in grains and other plant tissues and causes substantial economic losses throughout the world. DON is [...] Read more.
Fusarium head blight (FHB) of cereals is a severe disease caused by the Fusarium graminearum species complex. It leads to the accumulation of the mycotoxin deoxynivalenol (DON) in grains and other plant tissues and causes substantial economic losses throughout the world. DON is one of the most troublesome mycotoxins because it is a virulence factor to host plants, including wheat, and exhibits toxicity to plants and animals. To control both FHB and DON accumulation, a biological control approach using DON-degrading bacteria (DDBs) is promising. Here, we performed a disease control assay using an in vitro petri dish test composed of germinated wheat seeds inoculated with F. graminearum (Fg) and DDBs. Determination of both grown leaf lengths and hyphal lesion lengths as a measure of disease severity showed that the inoculation of seeds with the DDBs Devosia sp. strain NKJ1 and Nocardioides spp. strains SS3 or SS4 were protective against the leaf growth inhibition caused by Fg. Furthermore, it was as effective against DON accumulation. The inoculation with strains SS3 or SS4 also reduced the inhibitory effect on leaves treated with 10 µg mL−1 DON solution (without Fg). These results indicate that the DDBs partially suppress the disease by degrading DON. Full article
(This article belongs to the Special Issue Mycotoxins and Related Fungi in Crops)
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16 pages, 4398 KiB  
Article
Semiquantitation of Paralytic Shellfish Toxins by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry Using Relative Molar Response Factors
by Jiangbing Qiu, Elliott J. Wright, Krista Thomas, Aifeng Li, Pearse McCarron and Daniel G. Beach
Toxins 2020, 12(6), 398; https://doi.org/10.3390/toxins12060398 - 16 Jun 2020
Cited by 10 | Viewed by 3573
Abstract
Paralytic shellfish toxins (PSTs) are a complex class of analogs of the potent neurotoxin saxitoxin (STX). Since calibration standards are not available for many PSTs, including C-11 hydroxyl analogs called M-toxins, accurate quantitation by liquid chromatography–mass spectrometry (LC-MS) can be challenging. In [...] Read more.
Paralytic shellfish toxins (PSTs) are a complex class of analogs of the potent neurotoxin saxitoxin (STX). Since calibration standards are not available for many PSTs, including C-11 hydroxyl analogs called M-toxins, accurate quantitation by liquid chromatography–mass spectrometry (LC-MS) can be challenging. In the absence of standards, PSTs are often semiquantitated using standards of a different analog (e.g., STX), an approach with a high degree of uncertainty due to the highly variable sensitivity between analytes in electrospray ionization. Here, relative molar response factors (RMRs) were investigated for a broad range of PSTs using common LC-MS approaches in order to improve the quantitation of PSTs for which standards are unavailable. First, several M-toxins (M1-M6, M9 and dcM6) were semipurified from shellfish using preparative gel filtration chromatography and quantitated using LC-charged aerosol detection (LC-CAD). The RMRs of PST certified reference materials (CRMs) and M-toxins were then determined using selective reaction monitoring LC-MS/MS and full scan LC-high-resolution MS (LC-HRMS) methods in positive and negative electrospray ionization. In general, RMRs for PSTs with similar chemical structures were comparable, but varied significantly between subclasses, with M-toxins showing the lowest sensitivity. For example, STX showed a greater than 50-fold higher RMR than M4 and M6 by LC-HRMS. The MS instrument, scan mode and polarity also had significant impacts on RMRs and should be carefully considered when semiquantitating PSTs by LC-MS. As a demonstration of their utility, the RMRs determined were applied to the semiquantitation of PSTs in contaminated mussels, showing good agreement with results from calibration with CRMs. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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14 pages, 3075 KiB  
Article
Crystal Structure of Exotoxin A from Aeromonas Pathogenic Species
by Geoffrey Masuyer
Toxins 2020, 12(6), 397; https://doi.org/10.3390/toxins12060397 - 15 Jun 2020
Cited by 8 | Viewed by 4810
Abstract
Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The [...] Read more.
Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The X-ray crystal structure of AE was solved at 2.3 Å and presents all the hallmarks common to diphthamide-specific mono-ADP-ribosylating toxins, suggesting AE is a fourth member of this family alongside the diphtheria toxin, Pseudomonas exotoxin A and cholix. Structural homology indicates AE may use a similar mechanism of cytotoxicity that targets eukaryotic elongation factor 2 and thus inhibition of protein synthesis. The structure of AE also highlights unique features including a metal binding site, and a negatively charged cleft that could play a role in interdomain interactions and may affect toxicity. This study raises new opportunities to engineer alternative toxin-based molecules with pharmaceutical potential. Full article
(This article belongs to the Special Issue Selected Papers from the 26th Meeting of the French Society for Toxinology—Bioengineering of Toxins)
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21 pages, 2828 KiB  
Article
Chemical and Pharmacological Screening of Rhinella icterica (Spix 1824) Toad Parotoid Secretion in Avian Preparations
by Raquel Soares Oliveira, Bruna Trindade Borges, Allan Pinto Leal, Manuela Merlin Lailowski, Karla de Castro Figueiredo Bordon, Velci Queiróz de Souza, Lúcia Vinadé, Tiago Gomes dos Santos, Stephen Hyslop, Sidnei Moura, Eliane Candiani Arantes, Alexandre Pinto Corrado and Cháriston A. Dal Belo
Toxins 2020, 12(6), 396; https://doi.org/10.3390/toxins12060396 - 15 Jun 2020
Cited by 8 | Viewed by 3688
Abstract
The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, [...] Read more.
The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12β,25,26-tetrahydroxy-7-oxo-5β-cholestane-26-O-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and N-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick biventer cervicis neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na+/K+-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca2+ channels, leading to stabilization of the motor endplate membrane. Full article
(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)
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13 pages, 1557 KiB  
Article
Efficacy and Safety of Botulinum Toxin Type A on Persistent Myofascial Pain: A Randomized Clinical Trial
by Giancarlo De la Torre Canales, Natalia Alvarez-Pinzon, Victor Ricardo Manuel Muñoz-Lora, Leonardo Vieira Peroni, Amanda Farias Gomes, Alfonso Sánchez-Ayala, Francisco Haiter-Neto, Daniele Manfredini and Célia Marisa Rizzatti-Barbosa
Toxins 2020, 12(6), 395; https://doi.org/10.3390/toxins12060395 - 15 Jun 2020
Cited by 61 | Viewed by 6261
Abstract
This study assessed the safety and efficacy of three different doses of BoNT-A for persistent myofascial pain (MFP). One hundred female subjects were randomly assigned into five groups (n = 20): oral appliance (OA), saline solution (SS) and three BoNT-A groups with [...] Read more.
This study assessed the safety and efficacy of three different doses of BoNT-A for persistent myofascial pain (MFP). One hundred female subjects were randomly assigned into five groups (n = 20): oral appliance (OA), saline solution (SS) and three BoNT-A groups with different doses. Pain intensity and pressure pain threshold were evaluated up to 24 weeks after treatment. Adverse effects related to muscle contraction, masticatory performance, muscle thickness and mandibular bone volume were also assessed. Changes over time were compared within and between groups. The “nparLD” package and Wilcoxon signed-rank test were used to analyze the data. BoNT-A reduced pain intensity (p < 0.0001) and increased pressure pain threshold (p < 0.0001) for up to 24 weeks compared to the placebo. No differences were found between BoNT-A and OA at the last follow-up. A transient decline in masticatory performance (p < 0.05) and muscle contraction (p < 0.0001), and a decrease in muscle thickness (p < 0.05) and coronoid and condylar process bone volume (p < 0.05) were found as dose-related adverse effects of BoNT-A. Regardless of the dose, BoNT-A was as effective as OA on MFP. Notwithstanding, due to BoNT-A dose-related adverse effects, we suggest the use of low doses of BoNT-A in MFP patients that do not benefit from conservative treatments. Full article
(This article belongs to the Section Bacterial Toxins)
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3 pages, 185 KiB  
Editorial
Botulinum Toxin Paves the Way for the Treatment of Functional Lower Urinary Tract Dysfunction
by Hann-Chorng Kuo
Toxins 2020, 12(6), 394; https://doi.org/10.3390/toxins12060394 - 14 Jun 2020
Cited by 4 | Viewed by 2617
Abstract
Botulinum toxin A (BoNT-A) is a potent protein that can selectively modulate neurotransmission from nerve endings, resulting in the blocking of neurotransmitter releases and causing muscular paralysis [...] Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Pain and Inflammation in Functional Urological Disorders)
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