Toxins

11 pages, 2084 KiB

Open AccessArticle

A Structural Study on the Listeria Monocytogenes Internalin A—Human E-cadherin Interaction: A Molecular Tool to Investigate the Effects of Missense Mutations

by Luca Dellafiora, Virginia Filipello, Chiara Dall’Asta, Guido Finazzi, Gianni Galaverna and Marina Nadia Losio

Toxins 2020, 12(1), 60; https://doi.org/10.3390/toxins12010060 - 20 Jan 2020

Cited by 8 | Viewed by 4320

Abstract

Listeria monocytogenes is a widespread foodborne pathogen of high concern and internalin A is an important virulence factor that mediates cell invasion upon the interaction with the host protein E-cadherin. Nonsense mutations of internalin A are known to reduce virulence. Although missense mutations [...] Read more.

Listeria monocytogenes is a widespread foodborne pathogen of high concern and internalin A is an important virulence factor that mediates cell invasion upon the interaction with the host protein E-cadherin. Nonsense mutations of internalin A are known to reduce virulence. Although missense mutations are largely overlooked, they need to be investigated in respect to their effects in cell invasion processes. This work presented a computational workflow to early characterize internalin A missense mutations. The method reliably estimated the effects of a set of engineered missense mutations in terms of their effects on internalin A–E-cadherin interaction. Then, the effects of mutations of an internalin A variant from a L. monocytogenes isolate were calculated. Mutations showed impairing effects on complex stability providing a mechanistic explanation of the low cells invasion capacity previously observed. Overall, our results provided a rational approach to explain the effects of internalin A missense mutations. Moreover, our findings highlighted that the strength of interaction may not directly relate to the cell invasion capacity reflecting the non-exclusive role of internalin A in determining the virulence of L. monocytogenes. The workflow could be extended to other virulence factors providing a promising platform to support a better molecular understanding of L. monocytogenes epidemiology. Full article

(This article belongs to the Special Issue Toxins and Virulence Factors of Listeria monocytogenes)

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14 pages, 596 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Toxins in 2019

by Toxins Editorial Office

Toxins 2020, 12(1), 59; https://doi.org/10.3390/toxins12010059 - 19 Jan 2020

Viewed by 2626

Abstract

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article

12 pages, 913 KiB

Open AccessEditor’s ChoiceReview

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

by Britt Opdebeeck, Patrick C. D’Haese and Anja Verhulst

Toxins 2020, 12(1), 58; https://doi.org/10.3390/toxins12010058 - 19 Jan 2020

Cited by 42 | Viewed by 5854

Abstract

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired [...] Read more.

The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired coronary perfusion in the elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both IS and PCS trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation, coagulation, and lipid metabolism pathways, influenced by epigenetic factors, is crucial in IS/PCS-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by IS and PCS triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a number of important outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and vascular smooth muscle cells and new types of programmed cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed. Full article

(This article belongs to the Special Issue Comorbidities in Chronic Kidney Disease (CKD))

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13 pages, 2459 KiB

Open AccessArticle

Gas Chromatography–Mass Spectrometry Profiling of Volatile Compounds Reveals Metabolic Changes in a Non-Aflatoxigenic Aspergillus flavus Induced by 5-Azacytidine

by Fengqin Song, Qingru Geng, Xuewei Wang, Xiaoqing Gao, Xiaona He, Wei Zhao, Huahui Lan, Jun Tian, Kunlong Yang and Shihua Wang

Toxins 2020, 12(1), 57; https://doi.org/10.3390/toxins12010057 - 19 Jan 2020

Cited by 6 | Viewed by 3077

Abstract

Aspergillus flavus is one of the most opportunistic pathogens invading many important oilseed crops and foodstuffs with such toxic secondary metabolites as aflatoxin (AF) and Cyclopiazonic acid. We previously used the DNA methylation inhibitor 5-azacytidine to treat with an AF-producing A. flavus A133 [...] Read more.

Aspergillus flavus is one of the most opportunistic pathogens invading many important oilseed crops and foodstuffs with such toxic secondary metabolites as aflatoxin (AF) and Cyclopiazonic acid. We previously used the DNA methylation inhibitor 5-azacytidine to treat with an AF-producing A. flavus A133 strain, and isolated a mutant (NT) of A. flavus, which displayed impaired abilities of AF biosynthesis and fungal development. In this study, gas chromatography–mass spectrometry (GC-MS) analysis was used to reveal the metabolic changes between these two strains. A total of 1181 volatiles were identified in these two strains, among which 490 volatiles were found in these two strains in vitro and 332 volatiles were found in vivo. The NT mutant was found to produce decreasing volatile compounds, among which most of the fatty acid-derived volatiles were significantly downregulated in the NT mutant compared to the A133 strain, which are important precursors for AF biosynthesis. Two antioxidants and most of the amino acids derived volatiles were found significantly upregulated in the NT mutant. Overall, our results reveal the difference of metabolic profiles in two different A. flavus isolates, which may provide valuable information for controlling infections of this fungal pathogen. Full article

(This article belongs to the Section Mycotoxins)

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17 pages, 4615 KiB

Open AccessArticle

A Polyphasic Approach to Compare the Genomic Profiles of Aflatoxigenic and Non-Aflatoxigenic Isolates of Aspergillus Section Flavi

by Asmaa Abbas, Taha Hussien and Tapani Yli-Mattila

Toxins 2020, 12(1), 56; https://doi.org/10.3390/toxins12010056 - 16 Jan 2020

Cited by 11 | Viewed by 4505

Abstract

Aflatoxins (AF) are highly toxic compounds produced by Aspergillus section Flavi. They spoil food crops and present a serious global health hazard to humans and livestock. The aim of this study was to examine the phylogenetic relationships among aflatoxigenic and non-aflatoxigenic Aspergillus [...] Read more.

Aflatoxins (AF) are highly toxic compounds produced by Aspergillus section Flavi. They spoil food crops and present a serious global health hazard to humans and livestock. The aim of this study was to examine the phylogenetic relationships among aflatoxigenic and non-aflatoxigenic Aspergillus isolates. A polyphasic approach combining phylogenetic, sequence, and toxin analyses was applied to 40 Aspergillus section Flavi isolates collected from eight countries around the world (USA, Philippines, Egypt, India, Australia, Indonesia, China, and Uganda). This allows one to pinpoint the key genomic features that distinguish AF producing and non-producing isolates. Based on molecular identification, 32 (80%) were identified as A. flavus, three (7.5%) as A. parasiticus, three (7.5%) as A. nomius and one (2.5%) as A. tamarii. Toxin analysis showed that 22 (55%) Aspergillus isolates were aflatoxigenic. The majority of the toxic isolates (62.5%) originated from Egypt. The highest aflatoxin production potential was observed in an A. nomius isolate which is originally isolated from the Philippines. DNA-based molecular markers such as random amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) were used to evaluate the genetic diversity and phylogenetic relationships among these 40 Aspergillus isolates, which were originally selected from 80 isolates. The percentage of polymorphic bands in three RAPD and three ISSR primers was 81.9% and 79.37%, respectively. Analysis of molecular variance showed significant diversity within the populations, 92% for RAPD and 85% for ISSR primers. The average of Polymorphism Information Content (PIC), Marker Index (MI), Nei’s gene diversity (H) and Shannon’s diversity index (I) in ISSR markers are higher than those in RAPD markers. Based on banding patterns and gene diversities values, we observed that the ISSR-PCR provides clearer data and is more successful in genetic diversity analyses than RAPD-PCR. Dendrograms generated from UPGMA (Unweighted Pair Group Method with Arithmetic Mean) cluster analyses for RAPD and ISSR markers were related to the geographic origin. Full article

(This article belongs to the Special Issue Mycotoxins in Food: Origin and Management of Risk)

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14 pages, 3351 KiB

Open AccessArticle

Activation of the IRE1α Arm, but not the PERK Arm, of the Unfolded Protein Response Contributes to Fumonisin B1-Induced Hepatotoxicity

by Xiaoyi Liu, Enxiang Zhang, Shutao Yin, Chong Zhao, Lihong Fan and Hongbo Hu

Toxins 2020, 12(1), 55; https://doi.org/10.3390/toxins12010055 - 16 Jan 2020

Cited by 15 | Viewed by 3293

Abstract

Previous studies by us or others have shown that endoplasmic reticulum (ER) stress was activated by fumonisin 1 (FB1) exposure, which is considered to be a critical event in the FB1-induced toxic effect. However, the detailed mechanisms underlying FB1-induced ER stress-mediated liver toxicity [...] Read more.

Previous studies by us or others have shown that endoplasmic reticulum (ER) stress was activated by fumonisin 1 (FB1) exposure, which is considered to be a critical event in the FB1-induced toxic effect. However, the detailed mechanisms underlying FB1-induced ER stress-mediated liver toxicity remain elusive. The objectives of the present study were designed to address the following issues: (1) the contribution of each arm of the unfolded protein response (UPR); (2) the downstream targets of ER stress that mediated FB1-induced liver toxicity; and (3) the relationship between ER stress and oxidative stress triggered by FB1. We also investigated whether the inhibition of ER stress by its inhibitor could offer protection against FB1-induced hepatotoxicity in vivo, which has not been critically addressed previously. The results showed that the activation of the IRE1α axis, but not of the PERK axis, of UPR contributed to FB1-induced ER stress-mediated hepatocyte toxicity; the activation of the Bax/Bak-mediated mitochondrial pathway lay downstream of IRE1α to trigger mitochondrial-dependent apoptosis in response to FB1; FB1-induced oxidative stress and ER stress augmented each other through a positive feedback mechanism; tauroursodeoxycholic acid (TUDCA)-mediated ER stress inactivation is an effective approach to counteract FB1-induced hepatotoxicity in vivo. The data of the present study allow us to better understand the mechanisms of FB1-induced hepatotoxicity. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 1597 KiB

Open AccessArticle

Venomics and Cellular Toxicity of Thai Pit Vipers (Trimeresurus macrops and T. hageni)

by Supeecha Kumkate, Lawan Chanhome, Tipparat Thiangtrongjit, Jureeporn Noiphrom, Panithi Laoungboa, Orawan Khow, Taksa Vasaruchapong, Siravit Sitprija, Narongsak Chaiyabutr and Onrapak Reamtong

Toxins 2020, 12(1), 54; https://doi.org/10.3390/toxins12010054 - 16 Jan 2020

Cited by 10 | Viewed by 5366

Abstract

The two venomous pit vipers, Trimeresurus macrops and T. hageni, are distributed throughout Thailand, although their abundance varies among different areas. No species-specific antivenom is available for their bite victims, and the only recorded treatment method is a horse antivenom raised against [...] Read more.

The two venomous pit vipers, Trimeresurus macrops and T. hageni, are distributed throughout Thailand, although their abundance varies among different areas. No species-specific antivenom is available for their bite victims, and the only recorded treatment method is a horse antivenom raised against T. albolabris crude venom. To facilitate assessment of the cross-reactivity of heterologous antivenoms, protein profiles of T. macrops and T. hageni venoms were explored using mass-spectrometry-based proteomics. The results show that 185 and 216 proteins were identified from T. macrops and T. hageni venoms, respectively. Two major protein components in T. macrops and T. hageni venoms were snake venom serine protease and metalloproteinase. The toxicity of the venoms on human monocytes and skin fibroblasts was analyzed, and both showed a greater cytotoxic effect on fibroblasts than monocytic cells, with toxicity occurring in a dose-dependent rather than a time-dependent manner. Exploring the protein composition of snake venom leads to a better understanding of the envenoming of prey. Moreover, knowledge of pit viper venomics facilitates the selection of the optimum heterologous antivenoms for treating bite victims. Full article

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16 pages, 6888 KiB

Open AccessEditor’s ChoiceArticle

Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics

by Chunfang Xie, Julien Slagboom, Laura-Oana Albulescu, Ben Bruyneel, Kristina B. M. Still, Freek J. Vonk, Govert W. Somsen, Nicholas R. Casewell and Jeroen Kool

Toxins 2020, 12(1), 53; https://doi.org/10.3390/toxins12010053 - 16 Jan 2020

Cited by 19 | Viewed by 6287

Abstract

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused [...] Read more.

Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused by the multitude of injected toxins. In this study, the coagulopathic toxicities of venoms from the medically relevant snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus and Echis ocellatus were assessed. The venoms were separated by liquid chromatography (LC) followed by nanofractionation and parallel mass spectrometry (MS). A recently developed high-throughput coagulation assay was employed to assess both the pro- and anticoagulant activity of separated venom toxins. The neutralization capacity of antivenoms on separated venom components was assessed and the coagulopathic venom peptides and enzymes that were either neutralized or remained active in the presence of antivenom were identified by correlating bioassay results with the MS data and with off-line generated proteomics data. The results showed that most snake venoms analyzed contained both procoagulants and anticoagulants. Most anticoagulants were identified as phospholipases A₂s (PLA₂s) and most procoagulants correlated with snake venom metalloproteinases (SVMPs) and serine proteases (SVSPs). This information can be used to better understand antivenom neutralization and can aid in the development of next-generation antivenom treatments. Full article

(This article belongs to the Special Issue Medically Relevant Snake Toxins, Current Antivenoms and the Development of Next-Generation Antivenoms)

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10 pages, 817 KiB

Open AccessEditor’s ChoiceArticle

Patulin Mycotoxin in Mango and Orange Fruits, Juices, Pulps, and Jams Marketed in Pakistan

by Shabbir Hussain, Muhammad Rafique Asi, Mazhar Iqbal, Nisha Khalid, Syed Wajih-ul-Hassan and Agustín Ariño

Toxins 2020, 12(1), 52; https://doi.org/10.3390/toxins12010052 - 16 Jan 2020

Cited by 35 | Viewed by 5629

Abstract

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange [...] Read more.

The objective of the study was to explore the incidence of patulin (PAT) mycotoxin in mango and orange fruits and derived products marketed in Pakistan. A total of 274 samples, including 70 mango fruits, 63 mango-based products (juices, pulp, and jam), 77 orange fruits, and 64 orange-based products, were collected. PAT was determined by reverse-phase high-performance liquid chromatography (HPLC) with UV-Vis detector (276 nm). Linear detector response was observed (R² > 0.99), the limit of detection (LOD) was 5 µg/kg and recovery percentage was 97.4%. The incidence of PAT in mango samples was 61.7%, and the concentration ranged from <LOD to 6415 µg/kg with a mean of 110.9 µg/kg. Our results showed the high susceptibility of mango fruits to patulin, and it was observed that decayed mango fruits were most contaminated with PAT. Among the mango samples, PAT concentration was higher in fruits than in processed products such as mango juice, pulp, and jam. Toxin incidence in orange samples was 52.5% with concentrations from <LOD to 61 µg/kg and a mean of 6.3 µg/kg. As much as 29 samples of mango (21.8%) contained PAT concentration above the regulatory limit (50 µg/kg), whereas there was only one exceeding orange sample (0.7%). Our results show that PAT seems to be a problem in fruits, juices, and derived solid products, especially from mango, and needs surveillance on regular basis. Full article

(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)

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12 pages, 1198 KiB

Open AccessEditor’s ChoiceArticle

Dispersive Solid-Phase Extraction using Magnetic Carbon Nanotube Composite for the Determination of Emergent Mycotoxins in Urine Samples

by Natalia Arroyo-Manzanares, Rosa Peñalver-Soler, Natalia Campillo and Pilar Viñas

Toxins 2020, 12(1), 51; https://doi.org/10.3390/toxins12010051 - 15 Jan 2020

Cited by 17 | Viewed by 3692

Abstract

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and [...] Read more.

Dispersive magnetic solid-phase extraction (DMSPE) has received growing attention for sample treatment preconcentration prior to the separation of analytes due to its many advantages. In the present work, the potential of DMSPE for the determination of emergent mycotoxins (enniatins A, A1, B and B1, and beauvericin) is investigated for the first time. Different magnetic nanoparticles were tested and a magnetic multiwalled carbon nanotube (Fe₃O₄@MWCNT) composite was selected for the extraction and preconcentration of the five target mycotoxins in human urine samples before their analysis by ultrahigh performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). The nanocomposite was characterized by energy dispersive X-ray spectrometry, scanning electron microscopy, Fourier transform infrared spectrophotometry, and X-ray diffraction. Several parameters affecting the adsorption and desorption of DMSPE steps were optimized and the method was fully validated. Due to a matrix effect, matrix-matched calibration curves were necessary to carry out quantification. In this way, limits of quantification of between 0.04 and 0.1 μg/L, relative standard deviation values lower than 12% and recoveries between 89.3% and 98.9% were obtained. Finally, a study of the reuse of the Fe₃O₄@MWCNT composite was carried out, confirming that it can be reused at least four times. Full article

(This article belongs to the Special Issue Application of LC-MS/MS in the Mycotoxins Studies)

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21 pages, 1728 KiB

Open AccessEditor’s ChoiceReview

Ciguatera Fish Poisoning: The Risk from an Aotearoa/New Zealand Perspective

by Lesley L. Rhodes, Kirsty F. Smith, J. Sam Murray, Tomohiro Nishimura and Sarah C. Finch

Toxins 2020, 12(1), 50; https://doi.org/10.3390/toxins12010050 - 15 Jan 2020

Cited by 29 | Viewed by 4714

Abstract

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s [...] Read more.

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s northern subtropical coastline heighten the risk of Gambierdiscus proliferating in New Zealand. If this occurs, the risk of ciguatera fish poisoning due to consumption of locally caught fish will increase. Research, including the development and testing of sampling methods, molecular assays, and chemical and toxicity tests, will continue. Reliable monitoring strategies are important to manage and mitigate the risk posed by this emerging threat. The research approaches that have been made, many of which will continue, are summarised in this review. Full article

(This article belongs to the Special Issue Dinoflagellate Toxins)

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13 pages, 742 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Aflatoxin B₁ by a Sustainable Enzymatic Extract from Spent Mushroom Substrate of Pleurotus eryngii

by Maria Teresa Branà, Lucrezia Sergio, Miriam Haidukowski, Antonio F. Logrieco and Claudio Altomare

Toxins 2020, 12(1), 49; https://doi.org/10.3390/toxins12010049 - 14 Jan 2020

Cited by 41 | Viewed by 5386

Abstract

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every [...] Read more.

Ligninolytic enzymes from white-rot fungi, such as laccase (Lac) and Mn-peroxidase (MnP), are able to degrade aflatoxin B₁ (AFB1), the most harmful among the known mycotoxins. The high cost of purification of these enzymes has limited their implementation into practical technologies. Every year, tons of spent mushroom substrate (SMS) are produced as a by-product of edible mushroom cultivation, such as Pleurotus spp., and disposed at a cost for farmers. SMS may still bea source of ligninolytic enzymes useful for AFB1 degradation. The in vitro AFB1-degradative activity of an SMS crude extract (SMSE) was investigated. Results show that: (1) in SMSE, high Lac activity (4 U g⁻¹ dry matter) and low MnP activity (0.4 U g⁻¹ dry matter) were present; (2) after 1 d of incubation at 25 °C, the SMSE was able to degrade more than 50% of AFB1, whereas after 3 and 7 d of incubation, the percentage of degradation reached the values of 75% and 90%, respectively; (3) with increasing pH values, the degradation percentage increased, reaching 90% after 3 d at pH 8. Based on these results, SMS proved to be a suitable source of AFB1 degrading enzymes and the use of SMSE to detoxify AFB1 contaminated commodities appears conceivable. Full article

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18 pages, 2044 KiB

Open AccessArticle

Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of Escherichia coli O157:H7 during Host-Bacterial Interactions in vitro

by Andrea Cecilia Bruballa, Carolina Maiumi Shiromizu, Alan Mauro Bernal, Gonzalo Ezequiel Pineda, Florencia Sabbione, Analia Silvina Trevani, Leticia Verónica Bentancor, María Victoria Ramos, Romina Jimena Fernández-Brando, Manuel Javier Muñoz and Marina Sandra Palermo

Toxins 2020, 12(1), 48; https://doi.org/10.3390/toxins12010048 - 14 Jan 2020

Cited by 10 | Viewed by 4182

Abstract

Enterohemorrhagic Escherichia coli (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing E. coli O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells [...] Read more.

Enterohemorrhagic Escherichia coli (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing E. coli O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells participate in Stx2 production, cell damage, and inflammation during EHEC infection. With this aim, macrophage-differentiated THP-1 cells and the intestinal epithelial cell line HCT-8 were incubated with E. coli O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, stx₂ transcription, and cytokine secretion were analyzed in both human cell lines. We demonstrated that macrophages are able to internalize and kill EHEC. Simultaneously, Stx2 produced by internalized bacteria played a major role in macrophage death. In contrast, HCT-8 cells were completely resistant to EHEC infection. Besides, macrophages and HCT-8 infected cells produce IL-1β and IL-8 inflammatory cytokines, respectively. At the same time, bacterial stx₂-specific transcripts were detected only in macrophages after EHEC infection. The interplay between bacteria and host cells led to Stx production, triggering of inflammatory response and cell damage, all of which could contribute to a severe outcome after EHEC infections. Full article

(This article belongs to the Special Issue Pathogenesis of Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections)

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17 pages, 714 KiB

Open AccessArticle

Characterization of Venom Components and Their Phylogenetic Properties in Some Aculeate Bumblebees and Wasps

by Kyungjae Andrew Yoon, Kyungmun Kim, Woo-Jin Kim, Woo Young Bang, Neung-Ho Ahn, Chang-Hwan Bae, Joo-Hong Yeo and Si Hyeock Lee

Toxins 2020, 12(1), 47; https://doi.org/10.3390/toxins12010047 - 14 Jan 2020

Cited by 23 | Viewed by 4820

Abstract

To identify and compare venom components and expression patterns, venom gland-specific transcriptome analyses were conducted for 14 Aculeate bees and wasps. TPM (transcripts per kilobase million) values were normalized using the average transcription level of a reference housekeeping gene (dimethyladenosine transferase). Orthologous venom [...] Read more.

To identify and compare venom components and expression patterns, venom gland-specific transcriptome analyses were conducted for 14 Aculeate bees and wasps. TPM (transcripts per kilobase million) values were normalized using the average transcription level of a reference housekeeping gene (dimethyladenosine transferase). Orthologous venom component genes across the 14 bee and wasp species were identified, and their relative abundance in each species was determined by comparing normalized TPM values. Based on signal sequences in the transcripts, the genes of novel venom components were identified and characterized to encode potential allergens. Most of the allergens and pain-producing factors (arginine kinase, hyaluronidase, mastoparan, phospholipase A1, phospholipase A2, and venom allergen 5) showed extremely high expression levels in social wasps. Acid phosphatase, neprilysin, and tachykinin, which are known allergens and neurotoxic peptides, were found in the venom glands of solitary wasps more often than in social wasps. In the venom glands of bumblebees, few or no transcripts of major allergens or pain-producing factors were identified. Taken together, these results indicate that differential expression patterns of the venom genes in some Aculeate species imply that some wasps and bumblebee species have unique groups of highly expressed venom components. Some venom components reflected the Aculeate species phylogeny, but others did not. This unique evolution of specific venom components in different groups of some wasps and bumblebee species might have been shaped in response to both ecological and behavioral influences. Full article

(This article belongs to the Special Issue Evolutionary Ecology of Venom)

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14 pages, 2219 KiB

Open AccessArticle

Cellular Effects of T-2 Toxin on Primary Hepatic Cell Culture Models of Chickens

by Máté Mackei, Kata Orbán, Andor Molnár, László Pál, Károly Dublecz, Ferenc Husvéth, Zsuzsanna Neogrády and Gábor Mátis

Toxins 2020, 12(1), 46; https://doi.org/10.3390/toxins12010046 - 13 Jan 2020

Cited by 20 | Viewed by 4207

Abstract

Trichothecene mycotoxins such as T-2 toxin cause severe problems for agriculture, as well as for veterinary medicine. As liver is one of the key organs in metabolism, the main aim of our study was to investigate the immunomodulatory and cytotoxic effects of T-2 [...] Read more.

Trichothecene mycotoxins such as T-2 toxin cause severe problems for agriculture, as well as for veterinary medicine. As liver is one of the key organs in metabolism, the main aim of our study was to investigate the immunomodulatory and cytotoxic effects of T-2 toxin, using primary hepatocyte mono-culture and hepatocyte—nonparenchymal cell (predominantly Kupffer cell) co-culture models of chicken. Cultures were exposed to 10 (T10 group), 100 (T100 group) and 1000 (T1000 group) nmol/L T-2 toxin treatment for 8 or 24 h. Alterations of cellular metabolic activity, the production of reactive oxygen species (extracellular H₂O₂), heat shock protein 70 (HSP70), and the concentration of different inflammatory cytokines such as interleukin (IL-)6 and IL-8 were investigated. Metabolic activity was intensely decreased by T-2 toxin administration in all of the cell culture models, in every applied concentration and incubation time. Concentrations of HSP70 and IL-8 were significantly increased in hepatocyte mono-cultures exposed to higher T-2 toxin levels (both in T100 and T1000 groups for HSP70 and in T1000 group for IL-8, respectively) compared to controls after 24 h incubation. Similarly, IL-6 levels were also significantly elevated in the T100 and T1000 groups in both of mono- and co-cultures, but only after 8 h of incubation time. In spite of the general harmful effects of T-2 toxin treatment, no significant differences were observed on reactive oxygen species production. Furthermore, the two cell culture models showed different levels of H₂O₂, HSP70, and IL-8 concentrations independently of T-2 toxin supplementation. In conclusion, the established primary cell cultures derived from chicken proved to be proper models to study the specific molecular effects caused by T-2 toxin. Metabolic activity and immune status of the different examined cell cultures were intensively affected; however, no changes were found in H₂O₂ levels. Full article

(This article belongs to the Section Mycotoxins)

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12 pages, 305 KiB

Open AccessArticle

Circumstances and Consequences of Snakebite Envenomings: A Qualitative Study in South-Eastern Costa Rica

by Jazmín Arias-Rodríguez and José María Gutiérrez

Toxins 2020, 12(1), 45; https://doi.org/10.3390/toxins12010045 - 11 Jan 2020

Cited by 14 | Viewed by 3522

Abstract

A qualitative study was carried out in south-eastern Costa Rica on the circumstances and consequences of snakebite envenomings. This region has the highest incidence of snakebites and the lowest per capita and per family income in the country. There is a high degree [...] Read more.

A qualitative study was carried out in south-eastern Costa Rica on the circumstances and consequences of snakebite envenomings. This region has the highest incidence of snakebites and the lowest per capita and per family income in the country. There is a high degree of destitution and an unstable labor situation in the region. This study was based on semistructured interviews with 15 people who had suffered snakebite envenomings. This sample size was established on the basis of data saturation. Bites occurred mostly while doing agricultural work, either as salaried workers, as occasional workers, or working on their own. Although all people were attended in health centers of the public health system, and received antivenom free of charge, the majority of them did not receive compensation or rehabilitation upon discharge from the health facilities as a result of not being regular salaried workers. People described many difficulties as a consequence of these envenomings, such as permanent physical sequelae, including two amputations, psychological consequences, economic hardships, and difficulties for reinsertion into agricultural work. In spite of the significant advances that Costa Rica has made for reducing the impact of these envenomings, results reveal issues that require urgent attention by government and civil society organizations, to compensate for the physical, psychological, social, and economic consequences of these envenomings. Full article

(This article belongs to the Special Issue Long-Term Effects of Venom in Bites and Stings)

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18 pages, 4781 KiB

Open AccessArticle

New Insights into the Type II Toxins from the Sea Anemone Heteractis crispa

by Rimma S. Kalina, Steve Peigneur, Elena A. Zelepuga, Pavel S. Dmitrenok, Aleksandra N. Kvetkina, Natalia Y. Kim, Elena V. Leychenko, Jan Tytgat, Emma P. Kozlovskaya, Margarita M. Monastyrnaya and Irina N. Gladkikh

Toxins 2020, 12(1), 44; https://doi.org/10.3390/toxins12010044 - 10 Jan 2020

Cited by 16 | Viewed by 4436

Abstract

Toxins modulating Na_V channels are the most abundant and studied peptide components of sea anemone venom. Three type-II toxins, δ-SHTX-Hcr1f (= RpII), RTX-III, and RTX-VI, were isolated from the sea anemone Heteractis crispa. RTX-VI has been found to be an unusual [...] Read more.

Toxins modulating Na_V channels are the most abundant and studied peptide components of sea anemone venom. Three type-II toxins, δ-SHTX-Hcr1f (= RpII), RTX-III, and RTX-VI, were isolated from the sea anemone Heteractis crispa. RTX-VI has been found to be an unusual analog of RTX-III. The electrophysiological effects of Heteractis toxins on nine Na_V subtypes were investigated for the first time. Heteractis toxins mainly affect the inactivation of the mammalian Na_V channels expressed in the central nervous system (Na_V1.1–Na_V1.3, Na_V1.6) as well as insect and arachnid channels (BgNa_V1, VdNa_V1). The absence of Arg13 in the RTX-VI structure does not prevent toxin binding with the channel but it has changed its pharmacological profile and potency. According to computer modeling data, the δ-SHTX-Hcr1f binds within the extracellular region of the rNa_V1.2 voltage-sensing domain IV and pore-forming domain I through a network of strong interactions, and an additional fixation of the toxin at the channel binding site is carried out through the phospholipid environment. Our data suggest that Heteractis toxins could be used as molecular tools for Na_V channel studies or insecticides rather than as pharmacological agents. Full article

(This article belongs to the Special Issue Venoms and Ion Channels)

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16 pages, 6490 KiB

Open AccessEditor’s ChoiceArticle

T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

by Junhua Yang, Wenbo Guo, Jianhua Wang, Xianli Yang, Zhiqi Zhang and Zhihui Zhao

Toxins 2020, 12(1), 43; https://doi.org/10.3390/toxins12010043 - 10 Jan 2020

Cited by 45 | Viewed by 4973

Abstract

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission [...] Read more.

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis. Full article

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12 pages, 1736 KiB

Open AccessArticle

Development of An Innovative and Quick Method for the Isolation of Clostridium botulinum Strains Involved in Avian Botulism Outbreaks

by Thibault Le Gratiet, Typhaine Poezevara, Sandra Rouxel, Emmanuelle Houard, Christelle Mazuet, Marianne Chemaly and Caroline Le Maréchal

Toxins 2020, 12(1), 42; https://doi.org/10.3390/toxins12010042 - 10 Jan 2020

Cited by 8 | Viewed by 5772

Abstract

Avian botulism is a serious neuroparalytic disease mainly caused by a type C/D botulinum neurotoxin produced by Clostridium botulinum group III, one of the entwined bacterial species from the Clostridium novyi sensu lato genospecies. Its isolation is very challenging due to the absence [...] Read more.

Avian botulism is a serious neuroparalytic disease mainly caused by a type C/D botulinum neurotoxin produced by Clostridium botulinum group III, one of the entwined bacterial species from the Clostridium novyi sensu lato genospecies. Its isolation is very challenging due to the absence of selective media and the instability of the phage carrying the gene encoding for the neurotoxin. The present study describes the development of an original method for isolating C. botulinum group III strains. Briefly, this method consists of streaking the InstaGene matrix extraction pellet on Egg Yolk Agar plates and then collecting the colonies with lipase and lecithinase activities. Using this approach, it was possible to isolate 21 C. novyi sensu lato strains from 22 enrichment broths of avian livers, including 14 toxic strains. This method was successfully used to re-isolate type C, D, C/D, and D/C strains from liver samples spiked with five spores per gram. This method is cheap, user-friendly, and reliable. It can be used to quickly isolate toxic strains involved in avian botulism with a 64% success rate and C. novyi sensu lato with a 95% rate. This opens up new perspectives for C. botulinum genomic research, which will shed light on the epidemiology of avian botulism. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

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18 pages, 4983 KiB

Open AccessArticle

Aberrant Expressional Profiling of Known MicroRNAs in the Liver of Silver Carp (Hypophthalmichthys molitrix) Following Microcystin-LR Exposure Based on samllRNA Sequencing

by Yiyi Feng, Xi Chen, Junguo Ma, Bangjun Zhang and Xiaoyu Li

Toxins 2020, 12(1), 41; https://doi.org/10.3390/toxins12010041 - 9 Jan 2020

Cited by 7 | Viewed by 3052

Abstract

Microcystin-LR (MC-LR) poses a serious threat to human health due to its hepatotoxicity. However, the specific molecular mechanism of miRNAs in MC-LR-induced liver injury has not been determined. The aim of the present study was to determine whether miRNAs are regulated in MC-LR-induced [...] Read more.

Microcystin-LR (MC-LR) poses a serious threat to human health due to its hepatotoxicity. However, the specific molecular mechanism of miRNAs in MC-LR-induced liver injury has not been determined. The aim of the present study was to determine whether miRNAs are regulated in MC-LR-induced liver toxicity by using high-throughput sequencing. Our research demonstrated that 53 miRNAs and 319 miRNAs were significantly changed after 24 h of treatment with MC-LR (50 and 200 μg/kg, respectively) compared with the control group. GO enrichment analysis revealed that these target genes were related to cellular, metabolic, and single-organism processes. Furthermore, KEGG pathway analysis demonstrated that the target genes of differentially expressed miRNAs in fish liver were primarily involved in the insulin signaling pathway, PPAR signaling pathway, Wnt signaling pathway, and transcriptional misregulation in cancer. Moreover, we hypothesized that 4 miRNAs (miR-16, miR-181a-3p, miR-451, and miR-223) might also participate in MC-LR-induced toxicity in multiple organs of the fish and play regulatory roles according to the qPCR analysis results. Taken together, our results may help to elucidate the biological function of miRNAs in MC-LR-induced toxicity. Full article

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13 pages, 1854 KiB

Open AccessArticle

Isolation and Characterization of Cylindrospermopsis raciborskii Strains from Finished Drinking Water

by Carina Menezes, Elisabete Valério, Maria João Botelho and Elsa Dias

Toxins 2020, 12(1), 40; https://doi.org/10.3390/toxins12010040 - 8 Jan 2020

Cited by 6 | Viewed by 5151

Abstract

In the summer of 2015, an intense cyanobacterial bloom producing geosmin/2-methylisoborneol (MIB) occurred in the Roxo freshwater reservoir in Alentejo, Portugal. The drinking water supplied from the Roxo water treatment plant (WTP) exhibited an unpleasant odor/taste and a significant cyanobacteria density was detected [...] Read more.

In the summer of 2015, an intense cyanobacterial bloom producing geosmin/2-methylisoborneol (MIB) occurred in the Roxo freshwater reservoir in Alentejo, Portugal. The drinking water supplied from the Roxo water treatment plant (WTP) exhibited an unpleasant odor/taste and a significant cyanobacteria density was detected in the finished water at the exit of the WTP. Cyanobacteria were not evaluated downstream of the WTP, namely, at the city reservoir. The aim of this work was to isolate and characterize viable cyanobacteria present in finished water (exit of the WTP and city reservoir) that withstand conventional water treatment. Treated water samples collected at both sites were inoculated in Z8 culture medium to provide the conditions for putative cyanobacterial growth. After 30 days, filamentous cyanobacteria were observed in cultures inoculated with samples from the exit point of the WTP. Viable trichomes were isolated and identified as Cylindrospermopsis raciborskii by morphometric and molecular analysis. None of the isolates were cylindrospermopsin/microcystin producers, as confirmed by ELISA and amplification of corresponding genes (PS/PKS and mcyA-cd/mcyAB/mcyB). ELISA results were positive for saxitoxin, but saxitoxin and derivatives were not detected by liquid chromatography with fluorescence detection (LC-FLD), nor were their related genes (sxtA/sxtA4/sxtB/sxtM/sxtPer/sxtI). To our knowledge, this is the first report on the establishment of cultures of C. raciborskii that resisted water treatment processes. Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

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24 pages, 7147 KiB

Open AccessArticle

Morphological and Molecular Identification of Microcystin-Producing Cyanobacteria in Nine Shallow Bulgarian Water Bodies

by Mariana Radkova, Katerina Stefanova, Blagoy Uzunov, Georg Gärtner and Maya Stoyneva-Gärtner

Toxins 2020, 12(1), 39; https://doi.org/10.3390/toxins12010039 - 8 Jan 2020

Cited by 27 | Viewed by 6015

Abstract

The paper presents results from the first application of polyphasic approach in studies of field samples from Bulgaria. This approach, which combined the conventional light microscopy (LM) and molecular-genetic methods (based on PCR amplified fragments of microcystin synthetase gene mcyE), revealed that [...] Read more.

The paper presents results from the first application of polyphasic approach in studies of field samples from Bulgaria. This approach, which combined the conventional light microscopy (LM) and molecular-genetic methods (based on PCR amplified fragments of microcystin synthetase gene mcyE), revealed that almost all microcystin-producers in the studied eutrophic waterbodies belong to the genus Microcystis. During the molecular identification of toxin-producing strains by use of HEPF × HEPR pair of primers, we obtained 57 sequences, 56 of which formed 28 strains of Microcystis, spread in six clusters of the phylogenetic tree. By LM, seven Microcystis morphospecies were identified (M. aeruginosa, M. botrys, M. flos-aquae, M. natans, M. novacekii, M. smithii, and M. wesenbergii). They showed significant morphological variability and contributed from <1% to 98% to the total biomass. All data support the earlier opinions that taxonomic revision of Microcystis is needed, proved the presence of toxigenic strains in M. aeruginosa and M. wesenbergii, and suppose their existence in M. natans. Our results demonstrated also that genetic sequencing, and the use of HEPF × HEPR pair in particular, can efficiently serve in water quality monitoring for identifying the potential risk from microcystins, even in cases of low amounts of Microcystis in the water. Full article

(This article belongs to the Special Issue Selected Papers from the 11th International Conference on Toxic Cyanobacteria)

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14 pages, 1553 KiB

Open AccessArticle

An Inducible Cre-lox System to Analyze the Role of LLO in Listeria monocytogenes Pathogenesis

by Brittney N. Nguyen and Daniel A. Portnoy

Toxins 2020, 12(1), 38; https://doi.org/10.3390/toxins12010038 - 7 Jan 2020

Cited by 11 | Viewed by 4236

Abstract

Listeriolysin O (LLO) is a pore-forming cytolysin that allows Listeria monocytogenes to escape from phagocytic vacuoles and enter the host cell cytosol. LLO is expressed continuously during infection, but it has been a challenge to evaluate the importance of LLO secreted in the [...] Read more.

Listeriolysin O (LLO) is a pore-forming cytolysin that allows Listeria monocytogenes to escape from phagocytic vacuoles and enter the host cell cytosol. LLO is expressed continuously during infection, but it has been a challenge to evaluate the importance of LLO secreted in the host cell cytosol because deletion of the gene encoding LLO (hly) prevents localization of L. monocytogenes to the cytosol. Here, we describe a L. monocytogenes strain (hly^fl) in which hly is flanked by loxP sites and Cre recombinase is under the transcriptional control of the L. monocytogenes actA promoter, which is highly induced in the host cell cytosol. In less than 2 h after infection of bone marrow-derived macrophages (BMMs), bacteria were 100% non-hemolytic. hly^fl grew intracellularly to levels 10-fold greater than wildtype L. monocytogenes and was less cytotoxic. In an intravenous mouse model, 90% of bacteria were non-hemolytic within three hours in the spleen and eight hours in the liver. The loss of LLO led to a 2-log virulence defect in the spleen and a 4-log virulence defect in the liver compared to WT L. monocytogenes. Thus, the production of LLO in the cytosol has significant impact on the pathogenicity of L. monocytogenes. Full article

(This article belongs to the Special Issue Toxins and Virulence Factors of Listeria monocytogenes)

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19 pages, 2734 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Evaluation of the Efficiency of Yeast Cell Wall Extract to Adsorb Ochratoxin A and Mitigate Accumulation of the Toxin in Broiler Chickens

by Suvi Vartiainen, Alexandros Yiannikouris, Juha Apajalahti and Colm A. Moran

Toxins 2020, 12(1), 37; https://doi.org/10.3390/toxins12010037 - 7 Jan 2020

Cited by 21 | Viewed by 4340

Abstract

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) [...] Read more.

Ochratoxin A (OTA) is a common mycotoxin contaminant in animal feed. When absorbed from the gastrointestinal tract, OTA has a propensity for pathological effects on animal health and deposition in animal tissues. In this study, the potential of yeast cell wall extracts (YCWE) to adsorb OTA was evaluated using an in vitro method in which consecutive animal digestion events were simulated. Low pH markedly increased OTA binding to YCWE, which was reversed with a pH increased to 6.5. Overall, in vitro analysis revealed that 30% of OTA was adsorbed to YCWE. Additional computational molecular modelling revealed that change in pH alters the OTA charge and modulates the interaction with the YCWE β-d-glucans. The effectiveness of YCWE was tested in a 14-day broiler chicken trial. Birds were subjected to five dietary treatments; with and without OTA, and OTA combined with YCWE at three dosages. At the end of the trial, liver OTA deposition was evaluated. Data showed a decrease of up to 30% in OTA deposits in the liver of broilers fed both OTA and YCWE. In the case of OTA, a tight correlation between the mitigation efficacy of YCWE between in vitro and in vivo model could be observed. Full article

(This article belongs to the Special Issue Mycotoxin Exposure and Related Diseases)

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17 pages, 1688 KiB

Open AccessArticle

Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes

by Jean Louis Bossu, Laetitia Wioland, Frédéric Doussau, Philippe Isope, Michel R. Popoff and Bernard Poulain

Toxins 2020, 12(1), 36; https://doi.org/10.3390/toxins12010036 - 6 Jan 2020

Cited by 7 | Viewed by 3764

Abstract

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the [...] Read more.

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intracellular pathways that block the large conductance Kir channel activity in oligodendrocyte. Altogether, these findings and previous observations pinpoint oligodendrocytes as a major target for ETX. This supports the proposal that ETX might be a cause for Multiple Sclerosis, a disease characterized by myelin damage. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

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26 pages, 1038 KiB

Open AccessEditor’s ChoiceReview

Natural Sources and Bioactivities of 2,4-Di-Tert-Butylphenol and Its Analogs

by Fuqiang Zhao, Ping Wang, Rima D. Lucardi, Zushang Su and Shiyou Li

Toxins 2020, 12(1), 35; https://doi.org/10.3390/toxins12010035 - 6 Jan 2020

Cited by 180 | Viewed by 12352

Abstract

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and [...] Read more.

2,4-Di-tert-butylphenol or 2,4-bis(1,1-dimethylethyl)-phenol (2,4-DTBP) is a common toxic secondary metabolite produced by various groups of organisms. The biosources and bioactivities of 2,4-DTBP have been well investigated, but the phenol has not been systematically reviewed. This article provides a comprehensive review of 2,4-DTBP and its analogs with emphasis on natural sources and bioactivities. 2,4-DTBP has been found in at least 169 species of bacteria (16 species, 10 families), fungi (11 species, eight families), diatom (one species, one family), liverwort (one species, one family), pteridiphyta (two species, two families), gymnosperms (four species, one family), dicots (107 species, 58 families), monocots (22 species, eight families), and animals (five species, five families). 2,4-DTBP is often a major component of violate or essential oils and it exhibits potent toxicity against almost all testing organisms, including the producers; however, it is not clear why organisms produce autotoxic 2,4-DTBP and its analogs. The accumulating evidence indicates that the endocidal regulation seems to be the primary function of the phenols in the producing organisms. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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18 pages, 2757 KiB

Open AccessArticle

Variation in Occurrence and Aflatoxigenicity of Aspergillus flavus from Two Climatically Varied Regions in Kenya

by Ethel Monda, Joel Masanga and Amos Alakonya

Toxins 2020, 12(1), 34; https://doi.org/10.3390/toxins12010034 - 6 Jan 2020

Cited by 18 | Viewed by 4293

Abstract

Aflatoxins are carcinogenic chemical metabolites produced by Aspergillus spp. of the section Flavi. In Kenya, Aspergillus flavus is the most prevalent and has been associated with several acute and chronic aflatoxin outbreaks in the past. In this study, we evaluated the occurrence of [...] Read more.

Aflatoxins are carcinogenic chemical metabolites produced by Aspergillus spp. of the section Flavi. In Kenya, Aspergillus flavus is the most prevalent and has been associated with several acute and chronic aflatoxin outbreaks in the past. In this study, we evaluated the occurrence of A. flavus in soils from two agro-ecological regions with contrasting climatic conditions, aflatoxin contamination histories and cropping systems. Aspergillus spp. were first isolated from soils before the identification and determination of their aflatoxigenicity. Further, we determined the occurrence of Pseudomonas and Bacillus spp. in soils from the two regions. These bacterial species have long been associated with biological control of several plant pathogens including Aspergillus spp. Our results show that A. flavus occurred widely and produced comparatively higher total aflatoxin levels in all (100%) study sites from the eastern to the western regions of Kenya. For the western region, A. flavus was detected in 4 locations (66.7%) that were previously under maize cultivation with the isolates showing low aflatoxigenicity. A. flavus was not isolated from soils under sugarcane cultivation. Distribution of the two bacterial species varied across the regions but we detected a weak relationship between occurrence of bacterial species and A. flavus. We discuss these findings in the context of the influence of climate, microbial profiles, cropping systems and applicability in the deployment of biological control remedies against aflatoxin contamination. Full article

(This article belongs to the Special Issue Mycotoxigenic Fungi and Their Interactions with Plants)

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20 pages, 2382 KiB

Open AccessArticle

Phosphate Limitation Increases Content of Protease Inhibitors in the Cyanobacterium Microcystis aeruginosa

by Christian Burberg, Thomas Petzoldt and Eric von Elert

Toxins 2020, 12(1), 33; https://doi.org/10.3390/toxins12010033 - 6 Jan 2020

Cited by 10 | Viewed by 3837

Abstract

Increased anthropogenic nutrient input has led to eutrophication of lakes and ponds, resulting worldwide in more frequent and severe cyanobacterial blooms. In particular, enhanced availability of phosphorus (P) can promote cyanobacterial mass developments and may affect the content of secondary metabolites in cyanobacteria, [...] Read more.

Increased anthropogenic nutrient input has led to eutrophication of lakes and ponds, resulting worldwide in more frequent and severe cyanobacterial blooms. In particular, enhanced availability of phosphorus (P) can promote cyanobacterial mass developments and may affect the content of secondary metabolites in cyanobacteria, such as protease inhibitors (PIs). PIs are common among cyanobacteria and have been shown to negatively affect herbivorous zooplankton. Here, we test the hypothesis that P-limitation reduces the growth of Microcystis, but increases the content of PIs. In batch culture experiments with eight different initial phosphate concentrations (5–75 µM) we determined growth, stoichiometry, and PI content of Microcystis aeruginosa NIVA Cya 43. This strain produces the protease inhibitor BN920 that is converted by chlorination to CP954, which constitutes the major PI in this strain. C:N:P-ratios of the biomass indicated variation of P-limitation with treatment and time. When normalized to biomass, the PI content varied up to nearly nineteen-fold with treatment and time and was highest in the low-P treatments, especially during the mid-exponential growth phase. However, these effects were alleviated under nitrogen co-limitation. The content of CP954 showed an inverse u-shaped response to growth rate and C:N-ratio of the cyanobacterial biomass, whereas it increased with cyanobacterial C:P. The results indicate that P-limitation supports a higher content of defensive PIs and may indirectly foster cyanobacterial blooms by increasing the negative interference of cyanobacteria with their consumers. Full article

(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)

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14 pages, 820 KiB

Open AccessEditor’s ChoiceReview

Botulinum Neurotoxins and Cancer—A Review of the Literature

by Shivam O. Mittal and Bahman Jabbari

Toxins 2020, 12(1), 32; https://doi.org/10.3390/toxins12010032 - 5 Jan 2020

Cited by 28 | Viewed by 6845

Abstract

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the [...] Read more.

Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed. Full article

(This article belongs to the Special Issue Toxins and Cancer Therapy)

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30 pages, 2465 KiB

Open AccessMeeting Report

Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019

by Pascale Marchot, Sylvie Diochot, Michel R. Popoff and Evelyne Benoit

Toxins 2020, 12(1), 31; https://doi.org/10.3390/toxins12010031 - 3 Jan 2020

Viewed by 5307

Abstract

This 26th edition of the annual Meeting on Toxinology (RT26) of the SFET (http://sfet.asso.fr/international) was held at the Institut Pasteur of Paris on 4–5 December 2019 [...] 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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