Toxins

12 pages, 2893 KiB

Open AccessEditor’s ChoiceArticle

Decontamination of T-2 Toxin in Maize by Modified Montmorillonite Clay

by Bunmi K. Olopade, Solomon U. Oranusi, Obinna C. Nwinyi, Isiaka A. Lawal, Sefater Gbashi and Patrick B. Njobeh

Toxins 2019, 11(11), 616; https://doi.org/10.3390/toxins11110616 - 24 Oct 2019

Cited by 15 | Viewed by 3661

Abstract

Montmorillonite clay has a wide range of applications, one of which includes the binding of mycotoxins in foods and feeds through adsorption. T-2 toxin, produced by some Fusarium, Myrothecium, and Stachybotrys species, causes dystrophy in the brain, heart, and kidney. Various formulations that [...] Read more.

Montmorillonite clay has a wide range of applications, one of which includes the binding of mycotoxins in foods and feeds through adsorption. T-2 toxin, produced by some Fusarium, Myrothecium, and Stachybotrys species, causes dystrophy in the brain, heart, and kidney. Various formulations that include lemongrass essential oil-modified montmorillonite clay (LGEO-MMT), lemongrass powder (LGP), montmorillonite clay washed with 1 mM NaCl (Na-MMT), montmorillonite clay (MMT), and lemongrass powder mixed with montmorillonite clay (LGP-MMT) were applied to maize at concentrations of 8% and 12% and stored for a period of one month at 30 °C. Unmodified montmorillonite clay and LGP served as the negative controls alongside untreated maize. Fourier Transform Infrared (FTIR) spectra of the various treatments showed the major functional groups as Si-O and -OH. All treatment formulations were effective in the decontamination of T-2 toxin in maize. Accordingly, it was revealed that the inclusion of Na-MMT in maize at a concentration of 8% was most effective in decontaminating T-2 toxin by 66% in maize followed by LGP-MMT at 12% inclusion level recording a 56% decontamination of T-2 toxin in maize (p = 0.05). Montmorillonite clay can be effectively modified with plant extracts for the decontamination of T-2 toxin. Full article

(This article belongs to the Section Mycotoxins)

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12 pages, 1154 KiB

Open AccessEditor’s ChoiceArticle

Determination of Cyanotoxins and Phycotoxins in Seawater and Algae-Based Food Supplements Using Ionic Liquids and Liquid Chromatography with Time-Of-Flight Mass Spectrometry

by Claudia Giménez-Campillo, Marta Pastor-Belda, Natalia Campillo, Natalia Arroyo-Manzanares, Manuel Hernández-Córdoba and Pilar Viñas

Toxins 2019, 11(10), 610; https://doi.org/10.3390/toxins11100610 - 22 Oct 2019

Cited by 19 | Viewed by 4139

Abstract

An analytical procedure is proposed for determining three cyanotoxins (microcystin RR, microcystin LR, and nodularin) and two phycotoxins (domoic and okadaic acids) in seawater and algae-based food supplements. The toxins were first isolated by a salting out liquid extraction procedure. Since the concentration [...] Read more.

An analytical procedure is proposed for determining three cyanotoxins (microcystin RR, microcystin LR, and nodularin) and two phycotoxins (domoic and okadaic acids) in seawater and algae-based food supplements. The toxins were first isolated by a salting out liquid extraction procedure. Since the concentration expected in the samples was very low, a dispersive liquid–liquid microextraction procedure was included for preconcentration. The ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate (80 mg) was used as green extractant solvent and acetonitrile as disperser solvent (0.5 mL) for a 10 mL sample volume at pH 1.5, following the principles of green analytical chemistry. Liquid chromatography with electrospray ionization and quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) was used. The selectivity of the detection system, based on accurate mass measurements, allowed the toxins to be unequivocally identified. Mass spectra for quadrupole time of flight-mass spectrometry (Q-TOF-MS) and Q-TOF-MS/MS were recorded in the positive ion mode and quantification was based on the protonated molecule. Retention times ranged between 6.2 and 18.3 min using a mobile phase composed by a mixture of methanol and formic acid (0.1%). None of the target toxins were detected in any of the seawater samples analyzed, above their corresponding detection limits. However, microcystin LR was detected in the blue green alga sample. Full article

(This article belongs to the Special Issue Selected Papers from the 6th Iberian and 2nd Ibero-American Cyanotoxin Congress CIC2019)

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44 pages, 3949 KiB

Open AccessEditor’s ChoiceReview

Spider Venom: Components, Modes of Action, and Novel Strategies in Transcriptomic and Proteomic Analyses

by Nicolas Langenegger, Wolfgang Nentwig and Lucia Kuhn-Nentwig

Toxins 2019, 11(10), 611; https://doi.org/10.3390/toxins11100611 - 22 Oct 2019

Cited by 70 | Viewed by 12347

Abstract

This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis. Major venom component groups are small molecular mass compounds, antimicrobial (also called cytolytic, or cationic) peptides [...] Read more.

This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis. Major venom component groups are small molecular mass compounds, antimicrobial (also called cytolytic, or cationic) peptides (only in some spider families), cysteine-rich (neurotoxic) peptides, and enzymes and proteins. Cysteine-rich peptides are reviewed with respect to various structural motifs, their targets (ion channels, membrane receptors), nomenclature, and molecular binding. We further describe the latest findings concerning the maturation of antimicrobial, and cysteine-rich peptides that are in most known cases expressed as propeptide-containing precursors. Today, venom research, increasingly employs transcriptomic and mass spectrometric techniques. Pros and cons of venom gland transcriptome analysis with Sanger, 454, and Illumina sequencing are discussed and an overview on so far published transcriptome studies is given. In this respect, we also discuss the only recently described cross contamination arising from multiplexing in Illumina sequencing and its possible impacts on venom studies. High throughput mass spectrometric analysis of venom proteomes (bottom-up, top-down) are reviewed. Full article

(This article belongs to the Section Animal Venoms)

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23 pages, 5175 KiB

Open AccessEditor’s ChoiceArticle

Lipophilic Toxins in Galicia (NW Spain) between 2014 and 2017: Incidence on the Main Molluscan Species and Analysis of the Monitoring Efficiency

by Juan Blanco, Fabiola Arévalo, Jorge Correa and Ángeles Moroño

Toxins 2019, 11(10), 612; https://doi.org/10.3390/toxins11100612 - 22 Oct 2019

Cited by 26 | Viewed by 3305

Abstract

Galicia is an area with a strong mussel aquaculture industry in addition to other important bivalve mollusc fisheries. Between 2014 and 2017, 18,862 samples were analyzed for EU regulated marine lipophilic toxins. Okadaic acid (OA) was the most prevalent toxin and the only [...] Read more.

Galicia is an area with a strong mussel aquaculture industry in addition to other important bivalve mollusc fisheries. Between 2014 and 2017, 18,862 samples were analyzed for EU regulated marine lipophilic toxins. Okadaic acid (OA) was the most prevalent toxin and the only single toxin that produced harvesting closures. Toxin concentrations in raft mussels were generally higher than those recorded in other bivalves, justifying the use of this species as an indicator. The Rías of Pontevedra and Muros were the ones most affected by OA and DTX2 and the Ría of Ares by YTXs. In general, the outer areas of the Rías were more affected by OA and DTX2 than the inner ones. The OA level reached a maximum in spring, while DTX2 was almost entirely restricted to the fall–winter season. YTXs peaked in August–September. The toxins of the OA group were nearly completely esterified in all the bivalves studied except mussels and queen scallops. Risk of intoxication with the current monitoring system is low. In less than 2% of cases did the first detection of OA in an area exceed the regulatory limit. In no case, could any effect on humans be expected. The apparent intoxication and depuration rates were similar and directly related, suggesting that the rates are regulated mainly by oceanographic characteristics. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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17 pages, 3922 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Aflatoxin B₁ and Zearalenone by Bacterial and Fungal Laccases in Presence of Structurally Defined Chemicals and Complex Natural Mediators

by Xiaolu Wang, Yingguo Bai, Huoqing Huang, Tao Tu, Yuan Wang, Yaru Wang, Huiying Luo, Bin Yao and Xiaoyun Su

Toxins 2019, 11(10), 609; https://doi.org/10.3390/toxins11100609 - 22 Oct 2019

Cited by 55 | Viewed by 5542

Abstract

Aflatoxin B₁ (AFB₁) and zearalenone (ZEN) exert deleterious effects to human and animal health. In this study, the ability of a CotA laccase from Bacillus subtilis (BsCotA) to degrade these two mycotoxins was first investigated. Among the nine [...] Read more.

Aflatoxin B₁ (AFB₁) and zearalenone (ZEN) exert deleterious effects to human and animal health. In this study, the ability of a CotA laccase from Bacillus subtilis (BsCotA) to degrade these two mycotoxins was first investigated. Among the nine structurally defined chemical compounds, methyl syringate was the most efficient mediator assisting BsCotA to degrade AFB₁ (98.0%) and ZEN (100.0%). BsCotA could also use plant extracts, including the Epimedium brevicornu, Cucumis sativus L., Lavandula angustifolia, and Schizonepeta tenuifolia extracts to degrade AFB₁ and ZEN. Using hydra and BLYES as indicators, it was demonstrated that the degraded products of AFB₁ and ZEN using the laccase/mediator systems were detoxified. Finally, a laccase of fungal origin was also able to degrade AFB₁ and ZEN in the presence of the discovered mediators. The findings shed light on the possibility of using laccases and a mediator, particularly a natural plant-derived complex mediator, to simultaneously degrade AFB₁ and ZEN contaminants in food and feed. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 925 KiB

Open AccessEditor’s ChoicePerspective

The Mode of Action of Bacillus Species against Fusarium graminearum, Tools for Investigation, and Future Prospects

by Khayalethu Ntushelo, Lesiba Klaas Ledwaba, Molemi Evelyn Rauwane, Oluwafemi Ayodeji Adebo and Patrick Berka Njobeh

Toxins 2019, 11(10), 606; https://doi.org/10.3390/toxins11100606 - 18 Oct 2019

Cited by 46 | Viewed by 5662

Abstract

Fusarium graminearum is a pervasive plant pathogenic fungal species. Biological control agents employ various strategies to weaken their targets, as shown by Bacillus species, which adopt various mechanisms, including the production of bioactive compounds, to inhibit the growth of F. graminearum. Various [...] Read more.

Fusarium graminearum is a pervasive plant pathogenic fungal species. Biological control agents employ various strategies to weaken their targets, as shown by Bacillus species, which adopt various mechanisms, including the production of bioactive compounds, to inhibit the growth of F. graminearum. Various efforts to uncover the antagonistic mechanisms of Bacillus against F. graminearum have been undertaken and have yielded a plethora of data available in the current literature. This perspective article attempts to provide a unified record of these interesting findings. The authors provide background knowledge on the use of Bacillus as a biocontrol agent as well as details on techniques and tools for studying the antagonistic mechanism of Bacillus against F. graminearum. Emphasizing its potential as a future biological control agent with extensive use, the authors encourage future studies on Bacillus as a useful antagonist of F. graminearum and other plant pathogens. It is also recommended to take advantage of the newly invented analytical platforms for studying biochemical processes to understand the mechanism of action of Bacillus against plant pathogens in general. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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11 pages, 710 KiB

Open AccessEditor’s ChoiceArticle

Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence

by Gillian A.M. Tarr, Taryn Stokowski, Smriti Shringi, Phillip I. Tarr, Stephen B. Freedman, Hanna N. Oltean, Peter M. Rabinowitz and Linda Chui

Toxins 2019, 11(10), 607; https://doi.org/10.3390/toxins11100607 - 18 Oct 2019

Cited by 20 | Viewed by 4030

Abstract

Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes [...] Read more.

Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) −0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI −87.8%, −2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

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11 pages, 2943 KiB

Open AccessEditor’s ChoiceArticle

A Taxon-Specific and High-Throughput Method for Measuring Ligand Binding to Nicotinic Acetylcholine Receptors

by Christina N. Zdenek, Richard J. Harris, Sanjaya Kuruppu, Nicholas J. Youngman, James S. Dobson, Jordan Debono, Muzaffar Khan, Ian Smith, Mike Yarski, David Harrich, Charlotte Sweeney, Nathan Dunstan, Luke Allen and Bryan G. Fry

Toxins 2019, 11(10), 600; https://doi.org/10.3390/toxins11100600 - 16 Oct 2019

Cited by 32 | Viewed by 6997

Abstract

The binding of compounds to nicotinic acetylcholine receptors is of great interest in biomedical research. However, progress in this area is hampered by the lack of a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities of sample, or [...] Read more.

The binding of compounds to nicotinic acetylcholine receptors is of great interest in biomedical research. However, progress in this area is hampered by the lack of a high-throughput, cost-effective, and taxonomically flexible platform. Current methods are low-throughput, consume large quantities of sample, or are taxonomically limited in which targets can be tested. We describe a novel assay which utilizes a label-free bio-layer interferometry technology, in combination with adapted mimotope peptides, in order to measure ligand binding to the orthosteric site of nicotinic acetylcholine receptor alpha-subunits of diverse organisms. We validated the method by testing the evolutionary patterns of a generalist feeding species (Acanthophis antarcticus), a fish specialist species (Aipysurus laevis), and a snake specialist species (Ophiophagus hannah) for comparative binding to the orthosteric site of fish, amphibian, lizard, snake, bird, marsupial, and rodent alpha-1 nicotinic acetylcholine receptors. Binding patterns corresponded with diet, with the Acanthophis antarcticus not showing bias towards any particular lineage, while Aipysurus laevis showed selectivity for fish, and Ophiophagus hannah a selectivity for snake. To validate the biodiscovery potential of this method, we screened Acanthophis antarcticus and Tropidolaemus wagleri venom for binding to human alpha-1, alpha-2, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-9, and alpha-10. While A. antarcticus was broadly potent, T. wagleri showed very strong but selective binding, specifically to the alpha-1 target which would be evolutionarily selected for, as well as the alpha-5 target which is of major interest for drug design and development. Thus, we have shown that our novel method is broadly applicable for studies including evolutionary patterns of venom diversification, predicting potential neurotoxic effects in human envenomed patients, and searches for novel ligands of interest for laboratory tools and in drug design and development. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 3016 KiB

Open AccessEditor’s ChoiceArticle

Biological Stoichiometry Regulates Toxin Production in Microcystis aeruginosa (UTEX 2385)

by Nicole D. Wagner, Felicia S. Osburn, Jingyu Wang, Raegyn B. Taylor, Ashlynn R. Boedecker, C. Kevin Chambliss, Bryan W. Brooks and J. Thad Scott

Toxins 2019, 11(10), 601; https://doi.org/10.3390/toxins11100601 - 16 Oct 2019

Cited by 41 | Viewed by 5007

Abstract

Harmful algal blooms (HABs) are increasing in magnitude, frequency, and duration globally. Even though a limited number of phytoplankton species can be toxic, they are becoming one of the greatest water quality threats to public health and ecosystems due to their intrinsic toxicity [...] Read more.

Harmful algal blooms (HABs) are increasing in magnitude, frequency, and duration globally. Even though a limited number of phytoplankton species can be toxic, they are becoming one of the greatest water quality threats to public health and ecosystems due to their intrinsic toxicity to humans and the numerous interacting factors that undermine HAB forecasting. Here, we show that the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of a common toxic phytoplankton species, Microcystis, regulates toxin quotas during blooms through a tradeoff between primary and secondary metabolism. Populations with optimal C:N (< 8) and C:P (< 200) cellular stoichiometry consistently produced more toxins than populations exhibiting stoichiometric plasticity. Phosphorus availability in water exerted a strong control on population biomass and C:P stoichiometry, but N availability exerted a stronger control on toxin quotas by regulating population biomass and C:N:P stoichiometry. Microcystin-LR, like many phytoplankton toxins, is an N-rich secondary metabolite with a C:N stoichiometry that is similar to the optimal growth stoichiometry of Microcystis. Thus, N availability relative to P and light provides a dual regulatory mechanism that controls both biomass production and cellular toxin synthesis. Overall, our results provide a quantitative framework for improving forecasting of toxin production during HABs and compelling support for water quality management that limit both N and P inputs from anthropogenic sources. Full article

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

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19 pages, 3319 KiB

Open AccessEditor’s ChoiceArticle

Chemical Composition, Phytotoxic, Antimicrobial and Insecticidal Activity of the Essential Oils of Dracocephalum integrifolium

by Shixing Zhou, Caixia Wei, Chi Zhang, Caixia Han, Nigora Kuchkarova and Hua Shao

Toxins 2019, 11(10), 598; https://doi.org/10.3390/toxins11100598 - 13 Oct 2019

Cited by 38 | Viewed by 4415

Abstract

The present investigation studied the chemical composition of the essential oils extracted from Dracocephalum integrifolium Bunge growing in three different localities in northwest China and evaluated the phytotoxic, antimicrobial and insecticidal activities of the essential oils as well as their major constituents, i.e., [...] Read more.

The present investigation studied the chemical composition of the essential oils extracted from Dracocephalum integrifolium Bunge growing in three different localities in northwest China and evaluated the phytotoxic, antimicrobial and insecticidal activities of the essential oils as well as their major constituents, i.e., sabinene and eucalyptol. GC/MS analysis revealed the presence of 21–24 compounds in the essential oils, representing 94.17–97.71% of the entire oils. Monoterpenes were the most abundant substances, accounting for 85.30–93.61% of the oils; among them, sabinene (7.35–14.0%) and eucalyptol (53.56–76.11%) were dominant in all three oils, which occupied 67.56–83.46% of the total oils. In general, phytotoxic bioassays indicated that the IC₅₀ values of the oils and their major constituents were below 2 μL/mL (1.739–1.886 mg/mL) against Amaranthus retroflexus and Poa annua. Disc diffusion method demonstrated that the oils and their major constituents possessed antimicrobial activity against Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Saccharomyces cerevisiae, and Candida albicans, with MIC values ranging from 5–40 μL/mL (4.347–37.712 mg/mL). The oils, sabinene and eucalyptol also exhibited significant pesticidal activity, with the mortality rates of Aphis pomi reaching 100% after exposing to 10 μL oil/petri dish (8.694–9.428 mg/petri dish) for 24 h. To the best of our knowledge, this is the first report on the chemical composition, phytotoxic, antimicrobial and insecticidal activity of the essential oils extracted from D. integrifolium; it is noteworthy to mention that this is also the first report on the phytotoxicity of one of the major constituents, sabinene. Our results imply that D. integrifolium oils and sabinene have the potential value of being further exploited as natural pesticides. Full article

(This article belongs to the Special Issue Basic Research for the Potential Use of Plant Toxins)

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19 pages, 907 KiB

Open AccessEditor’s ChoiceArticle

Simultaneous Determination of Twenty Mycotoxins in the Korean Soybean Paste Doenjang by LC-MS/MS with Immunoaffinity Cleanup

by So Young Woo, So Young Ryu, Fei Tian, Sang Yoo Lee, Su Been Park and Hyang Sook Chun

Toxins 2019, 11(10), 594; https://doi.org/10.3390/toxins11100594 - 12 Oct 2019

Cited by 34 | Viewed by 5005

Abstract

Doenjang, a Korean fermented soybean paste, is vulnerable to contamination by mycotoxins because it is directly exposed to environmental microbiota during fermentation. A method that simultaneously determines 20 mycotoxins in doenjang, including aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEN), and fumonisins (FBs) with [...] Read more.

Doenjang, a Korean fermented soybean paste, is vulnerable to contamination by mycotoxins because it is directly exposed to environmental microbiota during fermentation. A method that simultaneously determines 20 mycotoxins in doenjang, including aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEN), and fumonisins (FBs) with an immunoaffinity column cleanup was optimized and validated in doenjang using LC-MS/MS. The method showed good performance in the analysis of 20 mycotoxins in doenjang with good linearity (R² > 0.999), intra- and inter-day precision (<16%), recovery (72–112%), matrix effect (87–104%), and measurement uncertainty (<42%). The validated method was applied to investigate mycotoxin contamination levels in commercial and homemade doenjang. The mycotoxins that frequently contaminated doenjang were AFs, OTA, ZEN, and FBs and the average contamination level and number of co-occurring mycotoxins in homemade doenjang were higher than those in commercially produced doenjang. Full article

(This article belongs to the Section Mycotoxins)

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20 pages, 1799 KiB

Open AccessEditor’s ChoiceReview

Cytolethal Distending Toxin Subunit B: A Review of Structure–Function Relationship

by Benoît J. Pons, Julien Vignard and Gladys Mirey

Toxins 2019, 11(10), 595; https://doi.org/10.3390/toxins11100595 - 12 Oct 2019

Cited by 41 | Viewed by 4503

Abstract

The Cytolethal Distending Toxin (CDT) is a bacterial virulence factor produced by several Gram-negative pathogenic bacteria. These bacteria, found in distinct niches, cause diverse infectious diseases and produce CDTs differing in sequence and structure. CDTs have been involved in the pathogenicity of the [...] Read more.

The Cytolethal Distending Toxin (CDT) is a bacterial virulence factor produced by several Gram-negative pathogenic bacteria. These bacteria, found in distinct niches, cause diverse infectious diseases and produce CDTs differing in sequence and structure. CDTs have been involved in the pathogenicity of the associated bacteria by promoting persistent infection. At the host-cell level, CDTs cause cell distension, cell cycle block and DNA damage, eventually leading to cell death. All these effects are attributable to the catalytic CdtB subunit, but its exact mode of action is only beginning to be unraveled. Sequence and 3D structure analyses revealed similarities with better characterized proteins, such as nucleases or phosphatases, and it has been hypothesized that CdtB exerts a biochemical activity close to those enzymes. Here, we review the relationships that have been established between CdtB structure and function, particularly by mutation experiments on predicted key residues in different experimental systems. We discuss the relevance of these approaches and underline the importance of further study in the molecular mechanisms of CDT toxicity, particularly in the context of different pathological conditions. Full article

(This article belongs to the Special Issue Current Knowledge on Bacterial Genotoxins and Their Effects on Host Cells)

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22 pages, 3488 KiB

Open AccessEditor’s ChoiceArticle

A Multiplex Analysis of Potentially Toxic Cyanobacteria in Lake Winnipeg during the 2013 Bloom Season

by Katelyn M. McKindles, Paul V. Zimba, Alexander S. Chiu, Susan B. Watson, Danielle B. Gutierrez, Judy Westrick, Hedy Kling and Timothy W. Davis

Toxins 2019, 11(10), 587; https://doi.org/10.3390/toxins11100587 - 11 Oct 2019

Cited by 16 | Viewed by 4045

Abstract

Lake Winnipeg (Manitoba, Canada), the world’s 12th largest lake by area, is host to yearly cyanobacterial harmful algal blooms (cHABs) dominated by Aphanizomenon and Dolichospermum. cHABs in Lake Winnipeg are primarily a result of eutrophication but may be exacerbated by the recent [...] Read more.

Lake Winnipeg (Manitoba, Canada), the world’s 12th largest lake by area, is host to yearly cyanobacterial harmful algal blooms (cHABs) dominated by Aphanizomenon and Dolichospermum. cHABs in Lake Winnipeg are primarily a result of eutrophication but may be exacerbated by the recent introduction of dreissenid mussels. Through multiple methods to monitor the potential for toxin production in Lake Winnipeg in conjunction with environmental measures, this study defined the baseline composition of a Lake Winnipeg cHAB to measure potential changes because of dreissenid colonization. Surface water samples were collected in 2013 from 23 sites during summer and from 18 sites in fall. Genetic data and mass spectrometry cyanotoxin profiles identified microcystins (MC) as the most abundant cyanotoxin across all stations, with MC concentrations highest in the north basin. In the fall, mcyA genes were sequenced to determine which species had the potential to produce MCs, and 12 of the 18 sites were a mix of both Planktothrix and Microcystis. Current blooms in Lake Winnipeg produce low levels of MCs, but the capacity to produce cyanotoxins is widespread across both basins. If dreissenid mussels continue to colonize Lake Winnipeg, a shift in physicochemical properties of the lake because of faster water column clearance rates may yield more toxic blooms potentially dominated by microcystin producers. Full article

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

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11 pages, 537 KiB

Open AccessEditor’s ChoiceArticle

Association between Serum Indoxyl Sulfate Levels and Endothelial Function in Non-Dialysis Chronic Kidney Disease

by Chih-Hsien Wang, Yu-Hsien Lai, Chiu-Huang Kuo, Yu-Li Lin, Jen-Pi Tsai and Bang-Gee Hsu

Toxins 2019, 11(10), 589; https://doi.org/10.3390/toxins11100589 - 11 Oct 2019

Cited by 23 | Viewed by 3018

Abstract

Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were [...] Read more.

Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were obtained from 110 patients with stages 3–5 CKD. The endothelial function, represented by vascular reactivity index (VRI), was measured non-invasively using digital thermal monitoring. Serum IS levels were determined using liquid chromatography–mass spectrometry. Twenty-one (19.1%), 36 (32.7%), and 53 (48.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. By univariate linear regression analysis, a higher prevalence of smoking, advanced age, higher systolic, and diastolic blood pressure (DBP), elevated levels of serum phosphorus, blood urea nitrogen, creatinine, and IS were negatively correlated with VRI values, but estimated glomerular filtration rate negatively associated with VRI values. After being adjusted by using multivariate stepwise linear regression analysis, DBP and IS levels were significantly negatively associated with VRI values in CKD patients. We concluded that IS level associated inversely with VRI values and had a modulating role in endothelial function in patients with stages 3–5 CKD. Full article

(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)

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11 pages, 2213 KiB

Open AccessEditor’s ChoiceArticle

An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses

by Mengyao Ji, Tengyu Zhu, Meichen Xing, Ning Luan, James Mwangi, Xiuwen Yan, Guoxiang Mo, Mingqiang Rong, Bowen Li, Ren Lai and Lin Jin

Toxins 2019, 11(10), 584; https://doi.org/10.3390/toxins11100584 - 10 Oct 2019

Cited by 25 | Viewed by 4988

Abstract

Flaviviruses are single-stranded RNA viruses predominantly transmitted by the widely distributed Aedes mosquitoes in nature. As important human pathogens, the geographic reach of Flaviviruses and their threats to public health are increasing, but there is currently no approved specific drug for treatment. In [...] Read more.

Flaviviruses are single-stranded RNA viruses predominantly transmitted by the widely distributed Aedes mosquitoes in nature. As important human pathogens, the geographic reach of Flaviviruses and their threats to public health are increasing, but there is currently no approved specific drug for treatment. In recent years, the development of peptide antivirals has gained much attention. Natural host defense peptides which uniquely evolved to protect the hosts have been shown to have antiviral properties. In this study, we firstly collected the venom of the Alopecosa nagpag spider from Shangri-La County, Yunnan Province. A defense peptide named Av-LCTX-An1a (Antiviral-Lycotoxin-An1a) was identified from the spider venom, and its anti-dengue serotype-2 virus (DENV2) activity was verified in vitro. Moreover, a real-time fluorescence-based protease inhibition assay showed that An1a functions as a DENV2 NS2B–NS3 protease inhibitor. Furthermore, we also found that An1a restricts zika virus (ZIKV) infection by inhibiting the ZIKV NS2B–NS3 protease. Together, our findings not only demonstrate that An1a might be a candidate for anti-flavivirus drug but also indicate that spider venom is a potential resource library rich in antiviral precursor molecules. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)

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16 pages, 1009 KiB

Open AccessEditor’s ChoiceReview

Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease

by Laetitia Dou and Noémie Jourde-Chiche

Toxins 2019, 11(10), 578; https://doi.org/10.3390/toxins11100578 - 5 Oct 2019

Cited by 36 | Viewed by 5317

Abstract

Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation [...] Read more.

Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease. Full article

(This article belongs to the Special Issue The Endothelial Effects of Uremic Toxins)

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17 pages, 2668 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Mycotoxin Occurrence in Maize Silage—A Neglected Risk for Bovine Gut Health?

by Nicole Reisinger, Sonja Schürer-Waldheim, Elisabeth Mayer, Sandra Debevere, Gunther Antonissen, Michael Sulyok and Veronika Nagl

Toxins 2019, 11(10), 577; https://doi.org/10.3390/toxins11100577 - 4 Oct 2019

Cited by 57 | Viewed by 5443

Abstract

Forages are important components of dairy cattle rations but might harbor a plethora of mycotoxins. Ruminants are considered to be less susceptible to the adverse health effects of mycotoxins, mainly because the ruminal microflora degrades certain mycotoxins. Yet, impairment of the ruminal degradation [...] Read more.

Forages are important components of dairy cattle rations but might harbor a plethora of mycotoxins. Ruminants are considered to be less susceptible to the adverse health effects of mycotoxins, mainly because the ruminal microflora degrades certain mycotoxins. Yet, impairment of the ruminal degradation capacity or high ruminal stability of toxins can entail that the intestinal epithelium is exposed to significant mycotoxin amounts. The aims of our study were to assess (i) the mycotoxin occurrence in maize silage and (ii) the cytotoxicity of relevant mycotoxins on bovine intestinal cells. In total, 158 maize silage samples were collected from European dairy cattle farms. LC-MS/MS-based analysis of 61 mycotoxins revealed the presence of emerging mycotoxins (e.g., emodin, culmorin, enniatin B1, enniatin B, and beauvericin) in more than 70% of samples. Among the regulated mycotoxins, deoxynivalenol and zearalenone were most frequently detected (67.7%). Overall, 87% of maize silages contained more than five mycotoxins. Using an in vitro model with calf small intestinal epithelial cells B, the cytotoxicity of deoxynivalenol, nivalenol, fumonisin B1 and enniatin B was evaluated (0–200 µM). Absolute IC50 values varied in dependence of employed assay and were 1.2–3.6 µM, 0.8–1.0 µM, 8.6–18.3 µM, and 4.0–6.7 µM for deoxynivalenol, nivalenol, fumonisin B1, and enniatin B, respectively. Results highlight the potential relevance of mycotoxins for bovine gut health, a previously neglected target in ruminants. Full article

(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)

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15 pages, 3079 KiB

Open AccessEditor’s ChoiceArticle

Occurrence and Seasonal Variations of Aflatoxin M₁ in Milk from Punjab, Pakistan

by Naveed Akbar, Muhammad Nasir, Naureen Naeem, Mansur-ud-Din Ahmad, Sanaullah Iqbal, Anjum Rashid, Muhammad Imran, Tanweer Aslam Gondal, Muhammad Atif, Bahare Salehi, Javad Sharifi-Rad, Miquel Martorell and William C. Cho

Toxins 2019, 11(10), 574; https://doi.org/10.3390/toxins11100574 - 2 Oct 2019

Cited by 24 | Viewed by 4860

Abstract

The manifestation of aflatoxins in feed and food is a major issue in the world as its presence leads to some health problems. This study investigates the incidence of aflatoxin M₁ (AFM₁) contamination in raw milk samples which were collected [...] Read more.

The manifestation of aflatoxins in feed and food is a major issue in the world as its presence leads to some health problems. This study investigates the incidence of aflatoxin M₁ (AFM₁) contamination in raw milk samples which were collected from Punjab, Pakistan. The Cluster Random Sampling technique was used to collect 960 milk samples from five different regions, and samples were collected every month. The AFM₁ level in raw milk was analyzed by the ELISA technique. The findings demonstrate that 70% of samples exceeded the United States permissible maximum residue limits (MRL 0.50 µg/L), with an overall AFM₁ level that ranged from 0.3 to 1.0 µg/L. AFM₁ contamination varied with the season: The highest average contamination was detected in winter (0.875 µg/L), followed by autumn (0.751 µg/L), spring (0.654 µg/L), and summer (0.455 µg/L). The Eastern region exhibited the highest average AFM₁ contamination (0.705 µg/L). Milk samples from the Northern region were found to be widely contaminated, as 86.9% samples exceeded the US MRL, followed by the Eastern region, with 72.3% samples being contaminated with >0.5 µg/L AFM₁. The study indicated that the raw milk supply chain was heavily contaminated. Recommendations and remedial measures need to be developed by regulatory authorities to improve the raw milk quality. Full article

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18 pages, 2412 KiB

Open AccessEditor’s ChoiceArticle

Determination of Selected Isoquinoline Alkaloids from Mahonia aquifolia; Meconopsis cambrica; Corydalis lutea; Dicentra spectabilis; Fumaria officinalis; Macleaya cordata Extracts by HPLC-DAD and Comparison of Their Cytotoxic Activity

by Anna Petruczynik, Tomasz Plech, Tomasz Tuzimski, Justyna Misiurek, Barbara Kaproń, Dorota Misiurek, Małgorzata Szultka-Młyńska, Bogusław Buszewski and Monika Waksmundzka-Hajnos

Toxins 2019, 11(10), 575; https://doi.org/10.3390/toxins11100575 - 2 Oct 2019

Cited by 31 | Viewed by 4193

Abstract

Alkaloids have protective functions for plants and can play an important role in living organisms. Alkaloids may have a wide range of pharmacological activities. Many of them have cytotoxic activity. Nowadays, cancer has become a serious public health problem. Searching for effective drugs [...] Read more.

Alkaloids have protective functions for plants and can play an important role in living organisms. Alkaloids may have a wide range of pharmacological activities. Many of them have cytotoxic activity. Nowadays, cancer has become a serious public health problem. Searching for effective drugs with anticancer activity is one of the most significant challenges of modern scientific research. The aim of this study was the investigation of cytotoxic activity of extracts obtained from Corydalis lutea root and herb, Dicentra spectabilis root and herb, Fumaria officinalis, Macleaya cordata leaves and herb, Mahonia aquifolia leaves and cortex, Meconopsis cambrica root and herb on FaDu, SCC-25, MCF-7, and MDA-MB-231 cancer cell lines. The cytotoxic activity of these extracts has not been previously tested for these cell lines. The aim was also to quantify selected alkaloids in the investigated extracts by High Performance Liquid Chromatography (HPLC). The analyses of alkaloid content were performed using HPLC in reversed phase (RP) mode using Polar RP column and mobile phase containing acetonitrile, water and ionic liquid (IL). Cytotoxic effect of the tested plant extracts and respective alkaloid standards were examined using human pharyngeal squamous carcinoma cells (FaDu), human tongue squamous carcinoma cells (SCC-25), human breast adenocarcinoma cell line (MCF-7), human triple-negative breast adenocarcinoma cell line (MDA-MB-231). All investigated plant extracts possess cytotoxic activity against tested cancer cell lines: FaDu, SCC-25, MCF-7, and MDA-MB-231. The highest cytotoxic activity against FaDu, SCC-25, and MCF-7 cell lines was estimated for Macleaya cordata leaf extract, while the highest cytotoxic activity against MDA-MB-231 cell line was obtained for Macleaya cordata herb extract. Differences in cytotoxic activity were observed for extracts obtained from various parts of investigated plants. In almost all cases the cytotoxic activity of investigated plant extracts, especially at the highest concentration against tested cell lines was significantly higher than the activity of anticancer drug etoposide. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments to confirm their anticancer activity. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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16 pages, 2442 KiB

Open AccessEditor’s ChoiceArticle

Degradation of Four Major Mycotoxins by Eight Manganese Peroxidases in Presence of a Dicarboxylic Acid

by Xiaolu Wang, Xing Qin, Zhenzhen Hao, Huiying Luo, Bin Yao and Xiaoyun Su

Toxins 2019, 11(10), 566; https://doi.org/10.3390/toxins11100566 - 27 Sep 2019

Cited by 70 | Viewed by 4811

Abstract

Enzymatic treatment is an attractive method for mycotoxin detoxification, which ideally prefers the use of one or a few enzymes. However, this is challenged by the diverse structures and co-contamination of multiple mycotoxins in food and feed. Lignin-degrading fungi have been discovered to [...] Read more.

Enzymatic treatment is an attractive method for mycotoxin detoxification, which ideally prefers the use of one or a few enzymes. However, this is challenged by the diverse structures and co-contamination of multiple mycotoxins in food and feed. Lignin-degrading fungi have been discovered to detoxify organics including mycotoxins. Manganese peroxidase (MnP) is a major enzyme responsible for lignin oxidative depolymerization in such fungi. Here, we demonstrate that eight MnPs from different lignocellulose-degrading fungi (five from Irpex lacteus, one from Phanerochaete chrysosporium, one from Ceriporiopsis subvermispora, and another from Nematoloma frowardii) could all degrade four major mycotoxins (aflatoxin B₁, AFB₁; zearalenone, ZEN; deoxynivalenol, DON; fumonisin B₁, FB₁) only in the presence of a dicarboxylic acid malonate, in which free radicals play an important role. The I. lacteus and C. subvermispora MnPs behaved similarly in mycotoxins transformation, outperforming the P. chrysosporium and N. frowardii MnPs. The large evolutionary diversity of these MnPs suggests that mycotoxin degradation tends to be a common feature shared by MnPs. MnP can, therefore, serve as a candidate enzyme for the degradation of multiple mycotoxins in food and feed if careful surveillance of the residual toxicity of degradation products is properly carried out. Full article

(This article belongs to the Section Mycotoxins)

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28 pages, 2809 KiB

Open AccessEditor’s ChoiceReview

Natural Occurrence in Venomous Arthropods of Antimicrobial Peptides Active against Protozoan Parasites

by Elias Ferreira Sabiá Júnior, Luis Felipe Santos Menezes, Israel Flor Silva de Araújo and Elisabeth Ferroni Schwartz

Toxins 2019, 11(10), 563; https://doi.org/10.3390/toxins11100563 - 25 Sep 2019

Cited by 28 | Viewed by 7231

Abstract

Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and [...] Read more.

Arthropoda is a phylum of invertebrates that has undergone remarkable evolutionary radiation, with a wide range of venomous animals. Arthropod venom is a complex mixture of molecules and a source of new compounds, including antimicrobial peptides (AMPs). Most AMPs affect membrane integrity and produce lethal pores in microorganisms, including protozoan pathogens, whereas others act on internal targets or by modulation of the host immune system. Protozoan parasites cause some serious life-threatening diseases among millions of people worldwide, mostly affecting the poorest in developing tropical regions. Humans can be infected with protozoan parasites belonging to the genera Trypanosoma, Leishmania, Plasmodium, and Toxoplasma, responsible for Chagas disease, human African trypanosomiasis, leishmaniasis, malaria, and toxoplasmosis. There is not yet any cure or vaccine for these illnesses, and the current antiprotozoal chemotherapeutic compounds are inefficient and toxic and have been in clinical use for decades, which increases drug resistance. In this review, we will present an overview of AMPs, the diverse modes of action of AMPs on protozoan targets, and the prospection of novel AMPs isolated from venomous arthropods with the potential to become novel clinical agents to treat protozoan-borne diseases. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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17 pages, 1347 KiB

Open AccessEditor’s ChoiceArticle

Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone

by Anna Rykaczewska, Magdalena Gajęcka, Ewa Onyszek, Katarzyna Cieplińska, Michał Dąbrowski, Sylwia Lisieska-Żołnierczyk, Maria Bulińska, Andrzej Babuchowski, Maciej T. Gajęcki and Łukasz Zielonka

Toxins 2019, 11(10), 561; https://doi.org/10.3390/toxins11100561 - 25 Sep 2019

Cited by 17 | Viewed by 2995

Abstract

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), [...] Read more.

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E₂) which, together with “free ZEN”, probably suppressed progesterone (P₄) and testosterone (T) levels. Full article

(This article belongs to the Special Issue Mycotoxins Occurence in Feed and Their Influence on Animal Health)

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25 pages, 1852 KiB

Open AccessEditor’s ChoiceReview

Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving

by Tarek Mohamed Abd El-Aziz, Antonio Garcia Soares and James D. Stockand

Toxins 2019, 11(10), 564; https://doi.org/10.3390/toxins11100564 - 25 Sep 2019

Cited by 120 | Viewed by 24907

Abstract

Animal venoms are used as defense mechanisms or to immobilize and digest prey. In fact, venoms are complex mixtures of enzymatic and non-enzymatic components with specific pathophysiological functions. Peptide toxins isolated from animal venoms target mainly ion channels, membrane receptors and components of [...] Read more.

Animal venoms are used as defense mechanisms or to immobilize and digest prey. In fact, venoms are complex mixtures of enzymatic and non-enzymatic components with specific pathophysiological functions. Peptide toxins isolated from animal venoms target mainly ion channels, membrane receptors and components of the hemostatic system with high selectivity and affinity. The present review shows an up-to-date survey on the pharmacology of snake-venom bioactive components and evaluates their therapeutic perspectives against a wide range of pathophysiological conditions. Snake venoms have also been used as medical tools for thousands of years especially in tradition Chinese medicine. Consequently, snake venoms can be considered as mini-drug libraries in which each drug is pharmacologically active. However, less than 0.01% of these toxins have been identified and characterized. For instance, Captopril^® (Enalapril), Integrilin^® (Eptifibatide) and Aggrastat^® (Tirofiban) are drugs based on snake venoms, which have been approved by the FDA. In addition to these approved drugs, many other snake venom components are now involved in preclinical or clinical trials for a variety of therapeutic applications. These examples show that snake venoms can be a valuable source of new principle components in drug discovery. Full article

(This article belongs to the Section Animal Venoms)

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18 pages, 1347 KiB

Open AccessEditor’s ChoiceReview

Chemical and Biological Characteristics of Antimicrobial α-Helical Peptides Found in Solitary Wasp Venoms and Their Interactions with Model Membranes

by Marcia Perez dos Santos Cabrera, Marisa Rangel, João Ruggiero Neto and Katsuhiro Konno

Toxins 2019, 11(10), 559; https://doi.org/10.3390/toxins11100559 - 24 Sep 2019

Cited by 20 | Viewed by 4037

Abstract

Solitary wasps use their stinging venoms for paralyzing insect or spider prey and feeding them to their larvae. We have surveyed bioactive substances in solitary wasp venoms, and found antimicrobial peptides together with some other bioactive peptides. Eumenine mastoparan-AF (EMP-AF) was the first [...] Read more.

Solitary wasps use their stinging venoms for paralyzing insect or spider prey and feeding them to their larvae. We have surveyed bioactive substances in solitary wasp venoms, and found antimicrobial peptides together with some other bioactive peptides. Eumenine mastoparan-AF (EMP-AF) was the first to be found from the venom of the solitary eumenine wasp Anterhynchium flavomarginatum micado, showing antimicrobial, histamine-releasing, and hemolytic activities, and adopting an α-helical secondary structure under appropriate conditions. Further survey of solitary wasp venom components revealed that eumenine wasp venoms contained such antimicrobial α-helical peptides as the major peptide component. This review summarizes the results obtained from the studies of these peptides in solitary wasp venoms and some analogs from the viewpoint of (1) chemical and biological characterization; (2) physicochemical properties and secondary structure; and (3) channel-like pore-forming properties. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

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18 pages, 1964 KiB

Open AccessEditor’s ChoiceArticle

Assessment of Fusarium Infection and Mycotoxin Contamination of Wheat Kernels and Flour Using Hyperspectral Imaging

by Elias Alisaac, Jan Behmann, Anna Rathgeb, Petr Karlovsky, Heinz-Wilhelm Dehne and Anne-Katrin Mahlein

Toxins 2019, 11(10), 556; https://doi.org/10.3390/toxins11100556 - 21 Sep 2019

Cited by 40 | Viewed by 7667

Abstract

Fusarium head blight (FHB) epidemics in wheat and contamination with Fusarium mycotoxins has become an increasing problem over the last decades. This prompted the need for non-invasive and non-destructive techniques to screen cereal grains for Fusarium infection, which is usually accompanied by mycotoxin [...] Read more.

Fusarium head blight (FHB) epidemics in wheat and contamination with Fusarium mycotoxins has become an increasing problem over the last decades. This prompted the need for non-invasive and non-destructive techniques to screen cereal grains for Fusarium infection, which is usually accompanied by mycotoxin contamination. This study tested the potential of hyperspectral imaging to monitor the infection of wheat kernels and flour with three Fusarium species. Kernels of two wheat varieties inoculated at anthesis with F. graminearum, F. culmorum, and F. poae were investigated. Hyperspectral images of kernels and flour were taken in the visible-near infrared (VIS-NIR) (400–1000 nm) and short-wave infrared (SWIR) (1000–2500 nm) ranges. The fungal DNA and mycotoxin contents were quantified. Spectral reflectance of Fusarium-damaged kernels (FDK) was significantly higher than non-inoculated ones. In contrast, spectral reflectance of flour from non-inoculated kernels was higher than that of FDK in the VIS and lower in the NIR and SWIR ranges. Spectral reflectance of kernels was positively correlated with fungal DNA and deoxynivalenol (DON) contents. In the case of the flour, this correlation exceeded r = −0.80 in the VIS range. Remarkable peaks of correlation appeared at 1193, 1231, 1446 to 1465, and 1742 to 2500 nm in the SWIR range. Full article

(This article belongs to the Section Mycotoxins)

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18 pages, 6885 KiB

Open AccessEditor’s ChoiceArticle

Effects of Essential Oil Citral on the Growth, Mycotoxin Biosynthesis and Transcriptomic Profile of Alternaria alternata

by Liuqing Wang, Nan Jiang, Duo Wang and Meng Wang

Toxins 2019, 11(10), 553; https://doi.org/10.3390/toxins11100553 - 20 Sep 2019

Cited by 50 | Viewed by 4692

Abstract

Alternaria alternata is a critical phytopathogen that causes foodborne spoilage and produces a polyketide mycotoxin, alternariol (AOH), and its derivative, alternariol monomethyl ether (AME). In this study, the inhibitory effects of the essential oil citral on the fungal growth and mycotoxin production of [...] Read more.

Alternaria alternata is a critical phytopathogen that causes foodborne spoilage and produces a polyketide mycotoxin, alternariol (AOH), and its derivative, alternariol monomethyl ether (AME). In this study, the inhibitory effects of the essential oil citral on the fungal growth and mycotoxin production of A. alternata were evaluated. Our findings indicated that 0.25 μL/mL (222.5 μg/mL) of citral completely suppressed mycelial growth as the minimum inhibitory concentration (MIC). Moreover, the 1/2MIC of citral could inhibit more than 97% of the mycotoxin amount. Transcriptomic profiling was performed by comparative RNA-Seq analysis of A. alternata with or without citral treatment. Out of a total of 1334 differentially expressed genes (DEGs), 621 up-regulated and 713 down-regulated genes were identified under citral stress conditions. Numerous DEGs for cell survival, involved in ribosome and nucleolus biogenesis, RNA processing and metabolic processes, and protein processing, were highly expressed in response to citral. However, a number of DEGs responsible for the metabolism of several carbohydrates and amino acids, sulfate and glutathione metabolism, the metabolism of xenobiotics and transporter activity were significantly more likely to be down-regulated. Citral induced the disturbance of cell integrity through the disorder of gene expression, which was further confirmed by the fact that exposure to citral caused irreversibly deleterious disruption of fungal spores and the inhibition of ergosterol biosynthesis. Citral perturbed the balance of oxidative stress, which was likewise verified by a reduction of total antioxidative capacity. In addition, citral was able to modulate the down-regulation of mycotoxin biosynthetic genes, including pksI and omtI. The results provide new insights for exploring inhibitory mechanisms and indicate citral as a potential antifungal and antimytoxigenic alternative for cereal storage. Full article

(This article belongs to the Special Issue Biocontrol Agents and Natural Compounds against Mycotoxinogenic Fungi)

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20 pages, 3864 KiB

Open AccessEditor’s ChoiceArticle

Synergistic Phytotoxic Effects of Culmorin and Trichothecene Mycotoxins

by Rebecca Wipfler, Susan P. McCormick, Robert Proctor, Jennifer Teresi, Guixia Hao, Todd Ward, Nancy Alexander and Martha M. Vaughan

Toxins 2019, 11(10), 555; https://doi.org/10.3390/toxins11100555 - 20 Sep 2019

Cited by 31 | Viewed by 4750

Abstract

Species of the fungus Fusarium cause Fusarium head blight (FHB) of cereal crops and contaminate grain with sesquiterpenoid mycotoxins, including culmorin (CUL) and trichothecenes. While the phytotoxicity of trichothecenes, such as deoxynivalenol (DON), and their role in virulence are well characterized, less is [...] Read more.

Species of the fungus Fusarium cause Fusarium head blight (FHB) of cereal crops and contaminate grain with sesquiterpenoid mycotoxins, including culmorin (CUL) and trichothecenes. While the phytotoxicity of trichothecenes, such as deoxynivalenol (DON), and their role in virulence are well characterized, less is known about the phytotoxicity of CUL and its role in the development of FHB. Herein, we evaluated the phytotoxic effects of purified CUL and CUL-trichothecene mixtures using Chlamydomonas reinhardtii growth and Triticum aestivum (wheat) root elongation assays. By itself, CUL did not affect growth in either system. However, mixtures of CUL with DON, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, or NX-3, but not with nivalenol, inhibited growth in a synergistic manner. Synergistic phytotoxic effects of CUL and DON were also observed on multiple plant varieties and species. The severity of wheat FHB caused by 15 isolates of Fusarium graminearum was negatively correlated with the CUL/DON ratio, but positively correlated with the sum of both CUL and DON. Additionally, during the first week of infection, CUL biosynthetic genes were more highly expressed than the TRI5 trichothecene biosynthetic gene. Furthermore, genomic analysis of Fusarium species revealed that CUL and trichothecene biosynthetic genes consistently co-occur among species closely related to F. graminearum. Full article

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

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9 pages, 2229 KiB

Open AccessEditor’s ChoiceCommunication

Graphene-Based Sensing Platform for On-Chip Ochratoxin A Detection

by Nikita Nekrasov, Dmitry Kireev, Aleksei Emelianov and Ivan Bobrinetskiy

Toxins 2019, 11(10), 550; https://doi.org/10.3390/toxins11100550 - 20 Sep 2019

Cited by 25 | Viewed by 5717

Abstract

In this work, we report an on-chip aptasensor for ochratoxin A (OTA) toxin detection that is based on a graphene field-effect transistor (GFET). Graphene-based devices are fabricated via large-scale technology, allowing for upscaling the sensor fabrication and lowering the device cost. The sensor [...] Read more.

In this work, we report an on-chip aptasensor for ochratoxin A (OTA) toxin detection that is based on a graphene field-effect transistor (GFET). Graphene-based devices are fabricated via large-scale technology, allowing for upscaling the sensor fabrication and lowering the device cost. The sensor assembly was performed through covalent bonding of graphene’s surface with an aptamer specifically sensitive towards OTA. The results demonstrate fast (within 5 min) response to OTA exposure with a linear range of detection between 4 ng/mL and 10 pg/mL, with a detection limit of 4 pg/mL. The regeneration time constant of the sensor was found to be rather small, only 5.6 s, meaning fast sensor regeneration for multiple usages. The high reproducibility of the sensing response was demonstrated via using several recycling procedures as well as various GFETs. The applicability of the aptasensor to real samples was demonstrated for spiked red wine samples with recovery of about 105% for a 100 pM OTA concentration; the selectivity of the sensor was also confirmed via addition of another toxin, zearalenone. The developed platform opens the way for multiplex sensing of different toxins using an on-chip array of graphene sensors. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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14 pages, 5510 KiB

Open AccessEditor’s ChoiceArticle

Fumonisins at Doses below EU Regulatory Limits Induce Histological Alterations in Piglets

by Chloé Terciolo, Ana Paula Bracarense, Pollyana C.M.C. Souto, Anne-Marie Cossalter, Léonie Dopavogui, Nicolas Loiseau, Carlos A. F. Oliveira, Philippe Pinton and Isabelle P. Oswald

Toxins 2019, 11(9), 548; https://doi.org/10.3390/toxins11090548 - 19 Sep 2019

Cited by 30 | Viewed by 3935

Abstract

Fumonisins (FBs) are mycotoxins produced by Fusarium species that can contaminate human food and animal feed. Due to the harmful effects of FBs on animals, the European Union (EU) defined a recommendation of a maximum of 5 mg FBs (B1 + B2)/kg for [...] Read more.

Fumonisins (FBs) are mycotoxins produced by Fusarium species that can contaminate human food and animal feed. Due to the harmful effects of FBs on animals, the European Union (EU) defined a recommendation of a maximum of 5 mg FBs (B1 + B2)/kg for complete feed for swine and 1 µg FBs/kg body weight per day as the tolerable daily intake for humans. The aim of this study was to evaluate the toxicity of dietary exposure to low doses of FBs, including a dose below the EU regulatory limits. Four groups of 24 weaned castrated male piglets were exposed to feed containing 0, 3.7, 8.1, and 12.2 mg/kg of FBs for 28 days; the impact was measured by biochemical analysis and histopathological observations. Dietary exposure to FBs at a low dose (3.7 mg/kg of feed) significantly increased the plasma sphinganine-to-sphingosine ratio. FBs-contaminated diets led to histological modifications in the intestine, heart, lung, lymphoid organs, kidney, and liver. The histological alterations in the heart and the intestine appeared at the lowest dose of FBs-contaminated diet (3.7 mg/kg feed) and in the kidney at the intermediate dose (8.1 mg/kg feed). At the highest dose tested (12.2 mg/kg feed), all the organs displayed histological alterations. This dose also induced biochemical modifications indicative of kidney and liver alterations. In conclusion, our data indicate that FBs-contaminated diets at doses below the EU regulatory limit cause histological lesions in several organs. This study suggests that EU recommendations for the concentration of FBs in animal feed, especially for swine, are not sufficiently protective and that regulatory doses should be modified for better protection of animal health. Full article

(This article belongs to the Section Mycotoxins)

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22 pages, 1192 KiB

Open AccessEditor’s ChoiceReview

Inhibition of Pore-Forming Proteins

by Neža Omersa, Marjetka Podobnik and Gregor Anderluh

Toxins 2019, 11(9), 545; https://doi.org/10.3390/toxins11090545 - 19 Sep 2019

Cited by 17 | Viewed by 5295

Abstract

Perforation of cellular membranes by pore-forming proteins can affect cell physiology, tissue integrity, or immune response. Since many pore-forming proteins are toxins or highly potent virulence factors, they represent an attractive target for the development of molecules that neutralize their actions with high [...] Read more.

Perforation of cellular membranes by pore-forming proteins can affect cell physiology, tissue integrity, or immune response. Since many pore-forming proteins are toxins or highly potent virulence factors, they represent an attractive target for the development of molecules that neutralize their actions with high efficacy. There has been an assortment of inhibitors developed to specifically obstruct the activity of pore-forming proteins, in addition to vaccination and antibiotics that serve as a plausible treatment for the majority of diseases caused by bacterial infections. Here we review a wide range of potential inhibitors that can specifically and effectively block the activity of pore-forming proteins, from small molecules to more specific macromolecular systems, such as synthetic nanoparticles, antibodies, antibody mimetics, polyvalent inhibitors, and dominant negative mutants. We discuss their mechanism of inhibition, as well as advantages and disadvantages. Full article

(This article belongs to the Special Issue Pore-Forming Toxins (PFTs): Never Out of Fashion)

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15 pages, 9442 KiB

Open AccessEditor’s ChoiceArticle

Astaxanthin Protects OTA-Induced Lung Injury in Mice through the Nrf2/NF-κB Pathway

by Weixiang Xu, Mingyang Wang, Gengyuan Cui, Lin Li, Danyang Jiao, Beibei Yao, Ketao Xu, Yueli Chen, Miao Long, Shuhua Yang and Jianbin He

Toxins 2019, 11(9), 540; https://doi.org/10.3390/toxins11090540 - 17 Sep 2019

Cited by 42 | Viewed by 4118

Abstract

The aim of this research was to evaluate the potential protective mechanism of astaxanthin (ASTA) against oxidative damage and inflammation caused by ochratoxin (OTA) in mouse lung. We divided mice into a control group (CG), an OTA group (PG), an astaxanthin group (AG), [...] Read more.

The aim of this research was to evaluate the potential protective mechanism of astaxanthin (ASTA) against oxidative damage and inflammation caused by ochratoxin (OTA) in mouse lung. We divided mice into a control group (CG), an OTA group (PG), an astaxanthin group (AG), and an OTA+ASTA group (JG). Oxidative indices (malondialdehyde (MDA), total superoxide dismutase (T-SOD), and reduced glutathione (GSH)) and inflammatory markers (interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α)) were assayed in the lung, and the lung-weight-to-body-weight ratio was calculated. Apoptosis was detected in pathological sections by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Oxidative damage and inflammation were detected in the lung of mice after exposure to OTA. Besides, Nrf2- and NF-κB-pathway-associated proteins were detected by Western blot. In contrast with OTA, ASTA significantly raised the expression of Nrf2, HO-1, and MnSOD, while the expression of other proteins (Keap1, TLR4, and NF-κB) was significantly decreased. These results indicate that ASTA exerted protective effects against OTA-induced oxidative damage and inflammation in the lung by regulating the Nrf2 and NF-κB pathways. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)

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20 pages, 2000 KiB

Open AccessEditor’s ChoiceArticle

Twenty-Eight Fungal Secondary Metabolites Detected in Pig Feed Samples: Their Occurrence, Relevance and Cytotoxic Effects In Vitro

by Barbara Novak, Valentina Rainer, Michael Sulyok, Dietmar Haltrich, Gerd Schatzmayr and Elisabeth Mayer

Toxins 2019, 11(9), 537; https://doi.org/10.3390/toxins11090537 - 14 Sep 2019

Cited by 21 | Viewed by 4667

Abstract

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant [...] Read more.

Feed samples are frequently contaminated by a wide range of chemically diverse natural products, which can be determined using highly sensitive analytical techniques. Next to already well-investigated mycotoxins, unknown or unregulated fungal secondary metabolites have also been found, some of which at significant concentrations. In our study, 1141 pig feed samples were analyzed for more than 800 secondary fungal metabolites using the same LC-MS/MS method and ranked according to their prevalence. Effects on the viability of the 28 most relevant were tested on an intestinal porcine epithelial cell line (IPEC-J2). The most frequently occurring compounds were determined as being cyclo-(L-Pro-L-Tyr), moniliformin, and enniatin B, followed by enniatin B1, aurofusarin, culmorin, and enniatin A1. The main mycotoxins, deoxynivalenol and zearalenone, were found only at ranks 8 and 10. Regarding cytotoxicity, apicidin, gliotoxin, bikaverin, and beauvericin led to lower IC₅₀ values, between 0.52 and 2.43 µM, compared to deoxynivalenol (IC₅₀ = 2.55 µM). Significant cytotoxic effects were also seen for the group of enniatins, which occurred in up to 82.2% of the feed samples. Our study gives an overall insight into the amount of fungal secondary metabolites found in pig feed samples compared to their cytotoxic effects in vitro. Full article

(This article belongs to the Special Issue Toxicological Effects of Mycotoxins on Target Cells)

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18 pages, 3319 KiB

Open AccessEditor’s ChoiceArticle

The Cadherin Cry1Ac Binding-Region is Necessary for the Cooperative Effect with ABCC2 Transporter Enhancing Insecticidal Activity of Bacillus thuringiensis Cry1Ac Toxin

by Yuemin Ma, Jianfeng Zhang, Yutao Xiao, Yanchao Yang, Chenxi Liu, Rong Peng, Yongbo Yang, Alejandra Bravo, Mario Soberón and Kaiyu Liu

Toxins 2019, 11(9), 538; https://doi.org/10.3390/toxins11090538 - 14 Sep 2019

Cited by 21 | Viewed by 4514

Abstract

Bacillus thuringiensis Cry1Ac toxin binds to midgut proteins, as cadherin (CAD) and ABCC2 transporter, to form pores leading to larval death. In cell lines, co-expression of CAD and ABCC2 enhance Cry1Ac toxicity significantly, but the mechanism remains elusive. Here, we show that the [...] Read more.

Bacillus thuringiensis Cry1Ac toxin binds to midgut proteins, as cadherin (CAD) and ABCC2 transporter, to form pores leading to larval death. In cell lines, co-expression of CAD and ABCC2 enhance Cry1Ac toxicity significantly, but the mechanism remains elusive. Here, we show that the expression of Helicoverpa armigera CAD (HaCAD-GFP) in Hi5 cells induces susceptibility to Cry1Ac and enhanced Cry1Ac toxicity when co-expressed with H. armigera ABCC2 (HaABCC2-GFP), since Cry1Ac toxicity increased 735-fold compared to Hi5 cells expressing HaCAD-GFP alone or 28-fold compared to HaABCC2-GFP alone. In contrast, the expression of the Spodoptera litura CAD (SlCAD-GFP) in Hi5 cells did not induce susceptibility to Cry1Ac nor it potentiated Cry1Ac toxicity with HaABCC2-GFP. To identify the CAD regions involved in the enhancement of Cry1Ac toxicity with ABCC2, the different CAD domains were replaced between SlCAD-GFP and HaCad-GFP proteins, and cytotoxicity assays were performed in Hi5 cells in the absence or presence of HaABCC2-GFP. The HaCAD toxin-binding region (TB), specifically the CAD repeat-11, was necessary to enhance Cry1Ac toxicity with ABCC2. We propose that CAD TB is involved in recruiting Cry1Ac to localize it in a good position for its interaction with the ABCC2, resulting in efficient toxin membrane insertion enhancing Cry1Ac toxicity. Full article

(This article belongs to the Special Issue Insecticidal Toxins from Bacillus thuringiensis)

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20 pages, 2446 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of Equine Staphylococcus aureus Isolates Exhibiting Reduced Oxacillin Susceptibility

by Anissa D. Scholtzek, Dennis Hanke, Birgit Walther, Inga Eichhorn, Sabita D. Stöckle, Katja-Sophia Klein, Heidrun Gehlen, Antina Lübke-Becker, Stefan Schwarz and Andrea T. Feßler

Toxins 2019, 11(9), 535; https://doi.org/10.3390/toxins11090535 - 13 Sep 2019

Cited by 24 | Viewed by 4276

Abstract

The detection of borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a challenge to both, veterinary and human laboratories. Between 2015 and 2017, 19 equine S. aureus with elevated minimal inhibitory concentrations for oxacillin were detected in routine diagnostics. The aim of this study was [...] Read more.

The detection of borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a challenge to both, veterinary and human laboratories. Between 2015 and 2017, 19 equine S. aureus with elevated minimal inhibitory concentrations for oxacillin were detected in routine diagnostics. The aim of this study was to characterize these isolates to identify factors possibly associated with the BORSA phenotype. All S. aureus were subjected to antimicrobial susceptibility testing and whole genome sequencing (WGS). A quantifiable β-lactamase activity assay was performed for a representative subset of 13 isolates. The WGS data analysis of the 19 BORSA isolates identified two different genomic lineages, sequence type (ST) 1 and ST1660. The core genome multilocus sequence typing (cgMLST) revealed a close relatedness of all isolates belonging to either ST1 or ST1660. The WGS analysis identified the resistance genes aadD, dfrG, tet(L), and/or blaZ and aacA-aphD. Phenotypic resistance to penicillins, aminoglycosides, tetracyclines, fluoroquinolones and sulfamethoxazole/trimethoprim was observed in the respective isolates. For the penicillin-binding proteins 1–4, amino acid substitutions were predicted using WGS data. Since neither transglycosylase nor transpeptidase domains were affected, these alterations might not explain the BORSA phenotype. Moreover, β-lactamase activity was found to be associated with an inducible blaZ gene. Lineage-specific differences regarding the expression profiles were noted. Full article

(This article belongs to the Special Issue Methicillin-Resistant Staphylococci and Macrococci at the Interface of Human and Animal Health)

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13 pages, 3211 KiB

Open AccessEditor’s ChoiceArticle

Structures of Reaction Products and Degradation Pathways of Aflatoxin B₁ by Ultrasound Treatment

by Yuanfang Liu, Mengmeng Li, Yuanxiao Liu and Ke Bian

Toxins 2019, 11(9), 526; https://doi.org/10.3390/toxins11090526 - 12 Sep 2019

Cited by 31 | Viewed by 3846

Abstract

Ultrasound is an emerging decontamination technology with potential use in the global food processing industry. In the present study, we explored power ultrasound for processing aqueous aflatoxin B₁ (AFB₁). AFB₁ was degraded by 85.1% after 80 min of ultrasound [...] Read more.

Ultrasound is an emerging decontamination technology with potential use in the global food processing industry. In the present study, we explored power ultrasound for processing aqueous aflatoxin B₁ (AFB₁). AFB₁ was degraded by 85.1% after 80 min of ultrasound exposure. The reaction products of AFB₁ were identified and their molecular formulae elucidated by ultra-high-performance liquid chromatography Q-Orbitrap mass spectrometry. Eight main reaction products were found, and their structures were clarified by parental ion fragmentation. Two degradation pathways were proposed according to the degradation product structures: One involved the addition of H• and OH• radicals, whereas the other involved H₂O₂ epoxidation and H•, OH•, and H₂O₂ oxidation of AFB₁. Ultrasound treatment significantly reduced AFB₁ bioactivity and toxicity by disrupting the C8=C9 double bond in the furan ring and modifying the lactone ring and methoxy group. Full article

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12 pages, 2304 KiB

Open AccessEditor’s ChoiceArticle

Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca²⁺/PP2A/AMPK Axis

by Jing-Ting Chiou, Yi-Jun Shi, Liang-Jun Wang, Chia-Hui Huang, Yuan-Chin Lee and Long-Sen Chang

Toxins 2019, 11(9), 527; https://doi.org/10.3390/toxins11090527 - 12 Sep 2019

Cited by 23 | Viewed by 3705

Abstract

Cardiotoxins (CTXs) are suggested to exert their cytotoxicity through cell membrane damage. Other studies show that penetration of CTXs into cells elicits mitochondrial fragmentation or lysosome disruption, leading to cell death. Considering the role of AMPK-activated protein kinase (AMPK) in mitochondrial biogenesis and [...] Read more.

Cardiotoxins (CTXs) are suggested to exert their cytotoxicity through cell membrane damage. Other studies show that penetration of CTXs into cells elicits mitochondrial fragmentation or lysosome disruption, leading to cell death. Considering the role of AMPK-activated protein kinase (AMPK) in mitochondrial biogenesis and lysosomal biogenesis, we aimed to investigate whether the AMPK-mediated pathway modulated Naja atra (Taiwan cobra) CTX3 cytotoxicity in U937 human leukemia cells. Our results showed that CTX3 induced autophagy and apoptosis in U937 cells, whereas autophagic inhibitors suppressed CTX3-induced apoptosis. CTX3 treatment elicited Ca²⁺-dependent degradation of the protein phosphatase 2A (PP2A) catalytic subunit (PP2Acα) and phosphorylation of AMPKα. Overexpression of PP2Acα mitigated the CTX3-induced AMPKα phosphorylation. CTX3-induced autophagy was via AMPK-mediated suppression of the Akt/mTOR pathway. Removal of Ca²⁺ or suppression of AMPKα phosphorylation inhibited the CTX3-induced cell death. CTX3 was unable to induce autophagy and apoptosis in U937 cells expressing constitutively active Akt. Met-modified CTX3 retained its membrane-perturbing activity, however, it did not induce AMPK activation and death of U937 cells. These results conclusively indicate that CTX3 induces autophagy and apoptosis in U937 cells via the Ca²⁺/PP2A/AMPK axis, and suggest that the membrane-perturbing activity of CTX3 is not crucial for the cell death signaling pathway induction. Full article

(This article belongs to the Section Animal Venoms)

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15 pages, 895 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of High-Resolution Mass Spectrometry for the Quantitative Analysis of Mycotoxins in Complex Feed Matrices

by Tolke Jensen, Marthe de Boevre, Nils Preußke, Sarah de Saeger, Tim Birr, Joseph-Alexander Verreet and Frank D. Sönnichsen

Toxins 2019, 11(9), 531; https://doi.org/10.3390/toxins11090531 - 12 Sep 2019

Cited by 23 | Viewed by 4128

Abstract

The selective and sensitive analysis of mycotoxins in highly complex feed matrices is a great challenge. In this study, the suitability of Orbitrap^TM-based high-resolution mass spectrometry (HRMS) for routine mycotoxin analysis in complex feeds was demonstrated by the successful validation of [...] Read more.

The selective and sensitive analysis of mycotoxins in highly complex feed matrices is a great challenge. In this study, the suitability of Orbitrap^TM-based high-resolution mass spectrometry (HRMS) for routine mycotoxin analysis in complex feeds was demonstrated by the successful validation of a full MS/data-dependent MS/MS acquisition method for the quantitative determination of eight Fusarium mycotoxins in forage maize and maize silage according to the Commission Decision 2002/657/EC. The required resolving power for accurate mass assignments (<5 ppm) was determined as 35,000 full width at half maximum (FWHM) and 70,000 FWHM for forage maize and maize silage, respectively. The recovery (R_A), intra-day precision (RSD_r), and inter-day precision (RSD_R) of measurements were in the range of 94 to 108%, 2 to 16%, and 2 to 12%, whereas the decision limit (CCα) and the detection capability (CCβ) varied from 11 to 88 µg/kg and 20 to 141 µg/kg, respectively. A set of naturally contaminated forage maize and maize silage samples collected in northern Germany in 2017 was analyzed to confirm the applicability of the HRMS method to real samples. At least four Fusarium mycotoxins were quantified in each sample, highlighting the frequent co-occurrence of mycotoxins in feed. Full article

(This article belongs to the Special Issue Advanced Methods for Mycotoxins Detection)

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23 pages, 951 KiB

Open AccessEditor’s ChoiceReview

Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches

by Christine Rasetti-Escargueil and Michel R. Popoff

Toxins 2019, 11(9), 528; https://doi.org/10.3390/toxins11090528 - 12 Sep 2019

Cited by 31 | Viewed by 10218

Abstract

Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a [...] Read more.

Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a substrate, which inhibits synaptic exocytotic transmitter release at neuro-muscular nerve endings leading to peripheral neuroparalysis of the skeletal and autonomic nervous systems. There are seven major serologically distinct toxinotypes (A–G) of BoNT which act on different substrates. Human botulism is generally caused by BoNT/A, B and E. Due to its extreme lethality and potential use as biological weapon, botulism remains a global public health concern. Vaccination against BoNT, although an effective strategy, remains undesirable due to the growing expectation around therapeutic use of BoNTs in various pathological conditions. This review focuses on the current approaches for botulism control by immunotherapy, highlighting the future challenges while the molecular underpinnings among subtypes variants and BoNT sequences found in non-clostridial species remain to be elucidated. Full article

(This article belongs to the Special Issue Characterization and Quantitative Analysis of Botulinum Neurotoxin)

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33 pages, 1826 KiB

Open AccessEditor’s ChoiceReview

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

by Lucie Hénaut, Alexandre Candellier, Cédric Boudot, Maria Grissi, Romuald Mentaverri, Gabriel Choukroun, Michel Brazier, Saïd Kamel and Ziad A. Massy

Toxins 2019, 11(9), 529; https://doi.org/10.3390/toxins11090529 - 12 Sep 2019

Cited by 33 | Viewed by 5262

Abstract

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells [...] Read more.

Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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11 pages, 1582 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin B₁ Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts

by Nathan Meijer, Geert Stoopen, H.J. van der Fels-Klerx, Joop J.A. van Loon, John Carney and Guido Bosch

Toxins 2019, 11(9), 532; https://doi.org/10.3390/toxins11090532 - 12 Sep 2019

Cited by 30 | Viewed by 6795

Abstract

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B₁ (AFB [...] Read more.

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B₁ (AFB₁), but recovery of total AFB₁ is less than 20% when accounting for its conversion to most known metabolites. The aim of this study was to examine the conversion of AFB₁ by S9 extracts of BSFL reared on substrates with or without AFB₁. Liver S9 of Aroclor-induced rats was used as a reference. To investigate whether cytochrome P450 enzymes are involved in the conversion of AFB₁, the inhibitor piperonyl butoxide (PBO) was tested in a number of treatments. The results showed that approximately 60% of AFB₁ was converted to aflatoxicol and aflatoxin P₁. The remaining 40% of AFB₁ was not converted. Cytochrome P450s were indeed responsible for metabolic conversion of AFB₁ into AFP₁, and a cytoplasmic reductase was most likely responsible for conversion of AFB₁ into aflatoxicol. Full article

(This article belongs to the Special Issue Mycotoxins in Feed and Food Chain: Present Status and Future Concerns)

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34 pages, 2898 KiB

Open AccessEditor’s ChoiceReview

The Diversity of Cyanobacterial Toxins on Structural Characterization, Distribution and Identification: A Systematic Review

by Xingde Du, Haohao Liu, Le Yuan, Yueqin Wang, Ya Ma, Rui Wang, Xinghai Chen, Michael D. Losiewicz, Hongxiang Guo and Huizhen Zhang

Toxins 2019, 11(9), 530; https://doi.org/10.3390/toxins11090530 - 12 Sep 2019

Cited by 104 | Viewed by 8768

Abstract

The widespread distribution of cyanobacteria in the aquatic environment is increasing the risk of water pollution caused by cyanotoxins, which poses a serious threat to human health. However, the structural characterization, distribution and identification techniques of cyanotoxins have not been comprehensively reviewed in [...] Read more.

The widespread distribution of cyanobacteria in the aquatic environment is increasing the risk of water pollution caused by cyanotoxins, which poses a serious threat to human health. However, the structural characterization, distribution and identification techniques of cyanotoxins have not been comprehensively reviewed in previous studies. This paper aims to elaborate the existing information systematically on the diversity of cyanotoxins to identify valuable research avenues. According to the chemical structure, cyanotoxins are mainly classified into cyclic peptides, alkaloids, lipopeptides, nonprotein amino acids and lipoglycans. In terms of global distribution, the amount of cyanotoxins are unbalanced in different areas. The diversity of cyanotoxins is more obviously found in many developed countries than that in undeveloped countries. Moreover, the threat of cyanotoxins has promoted the development of identification and detection technology. Many emerging methods have been developed to detect cyanotoxins in the environment. This communication provides a comprehensive review of the diversity of cyanotoxins, and the detection and identification technology was discussed. This detailed information will be a valuable resource for identifying the various types of cyanotoxins which threaten the environment of different areas. The ability to accurately identify specific cyanotoxins is an obvious and essential aspect of cyanobacterial research. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Identification and Structural Characterisation to Better Understand Their Distribution and Diversity)

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15 pages, 1415 KiB

Open AccessEditor’s ChoiceArticle

Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach

by Johanna Alberts, Gerd Schatzmayr, Wulf-Dieter Moll, Ibtisaam Davids, John Rheeder, Hester-Mari Burger, Gordon Shephard and Wentzel Gelderblom

Toxins 2019, 11(9), 523; https://doi.org/10.3390/toxins11090523 - 10 Sep 2019

Cited by 24 | Viewed by 4802

Abstract

Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme^®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by [...] Read more.

Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme^®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by de-esterification, was utilised to develop an enzymatic reduction method in a maize kernel enzyme incubation mixture. Efficacy of the FumD FB reduction method in “low” and “high” FB contaminated home-grown maize was compared by monitoring FB₁ hydrolysis to the hydrolysed FB₁ (HFB₁) product utilising a validated LC-MS/MS analytical method. The method was further evaluated in terms of enzyme activity and treatment duration by assessing enzyme kinetic parameters and the relative distribution of HFB₁ between maize kernels and the residual aqueous environment. FumD treatments resulted in significant reduction (≥80%) in “low” (≥1000 U/L, p < 0.05) and “high” (100 U/L, p < 0.05; ≥1000 U/L, p < 0.0001) FB contaminated maize after 1 h respectively, with an approximate 1:1 µmol conversion ratio of FB₁ into the formation of HFB₁. Enzyme kinetic parameters indicated that, depending on the activity of FumD utilised, a significantly (p < 0.05) higher FB₁ conversion rate was noticed in “high” FB contaminated maize. The FumD FB reduction method in maize could find application in commercial maize-based practices as well as in communities utilising home-grown maize as a main dietary staple and known to be exposed above the tolerable daily intake levels. Full article

(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)

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17 pages, 1469 KiB

Open AccessEditor’s ChoiceReview

Modifying Phosphate Toxicity in Chronic Kidney Disease

by Marc Vervloet

Toxins 2019, 11(9), 522; https://doi.org/10.3390/toxins11090522 - 9 Sep 2019

Cited by 13 | Viewed by 5093

Abstract

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder [...] Read more.

Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

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22 pages, 1889 KiB

Open AccessEditor’s ChoiceArticle

Development of an UPLC-MS/MS Method for the Analysis of Mycotoxins in Rumen Fluid with and without Maize Silage Emphasizes the Importance of Using Matrix-Matched Calibration

by Sandra Debevere, Siegrid De Baere, Geert Haesaert, Michael Rychlik, Veerle Fievez and Siska Croubels

Toxins 2019, 11(9), 519; https://doi.org/10.3390/toxins11090519 - 7 Sep 2019

Cited by 19 | Viewed by 4792

Abstract

Ruminants are less susceptible to the effects of mycotoxins than monogastric animals as their rumen microbiota are claimed to degrade and/or deactivate at least some of these toxic compounds. However, the mycotoxin degradation is not well-known yet. For this, a sensitive, specific, and [...] Read more.

Ruminants are less susceptible to the effects of mycotoxins than monogastric animals as their rumen microbiota are claimed to degrade and/or deactivate at least some of these toxic compounds. However, the mycotoxin degradation is not well-known yet. For this, a sensitive, specific, and accurate analytical method is needed to determine mycotoxins in the rumen fluid. This study aims to develop and thoroughly validate an ultra-performance liquid chromatography tandem mass spectrometry method for the quantitative determination in the rumen fluid of some of the most relevant mycotoxins found in maize silage in Western Europe: deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEN), mycophenolic acid (MPA), roquefortine C (ROQ-C) and enniatin B (ENN B), as well as their metabolites deepoxy-deoxynivalenol (DOM-1), α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), zearalanone (ZAN), α-zearalanol (α-ZAL) and β-zearalanol (β-ZAL). As feed is often present in the rumen fluid samples, the potential interaction of feed particles with the mycotoxin extraction and analysis was investigated. Extraction recovery and matrix effects were determined in the rumen fluid with and without maize silage. Differences in those parameters between rumen fluid alone and rumen fluid with maize silage highlight the importance of using matrix-matched calibration curves for the quantification of mycotoxins in rumen fluid samples. A cross-validation of the method with rumen fluid and maize silage demonstrates that this analytical method can be applied in research on rumen fluid samples to investigate the degradation of the reported mycotoxins by rumen microbiota if matrix-matched calibration is performed. Full article

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

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13 pages, 1430 KiB

Open AccessEditor’s ChoiceArticle

Serrulin: A Glycine-Rich Bioactive Peptide from the Hemolymph of the Yellow Tityus serrulatus Scorpion

by Thiago de Jesus Oliveira, Ursula Castro de Oliveira and Pedro Ismael da Silva Junior

Toxins 2019, 11(9), 517; https://doi.org/10.3390/toxins11090517 - 6 Sep 2019

Cited by 17 | Viewed by 4549

Abstract

Antimicrobial peptides (AMPs) are small molecules, which have a potential use as antibiotic or pharmacological tools. In chelicerate organisms, such as scorpions, these molecules constitute an alternative defense system against microorganisms. The aim of this work was to identify AMPs in the hemolymph [...] Read more.

Antimicrobial peptides (AMPs) are small molecules, which have a potential use as antibiotic or pharmacological tools. In chelicerate organisms, such as scorpions, these molecules constitute an alternative defense system against microorganisms. The aim of this work was to identify AMPs in the hemolymph of the Tityus serrulatus scorpion. Fractions of plasma and hemocytes were subjected to high-performance liquid chromatography (HPLC) and then analyzed to determine their activity in inhibiting microbial growth. One of the fractions from the hemocytes presents antimicrobial activity against microorganisms, such as Gram-negative and Gram-positive bacteria, fungi, and yeast. These fractions were analyzed by mass spectrometry, and a fragment of 3564 Da. was identified. The peptide was called serrulin, because it is derived from the species T. serrulatus. A comparison of the amino acid sequence of serrulin with databases shows that it has a similarity to the glycine-rich peptides described in Cupienius salai and Acanthoscurria gomesiana (spiders). Furthermore, serrulin has no hemolytic activity against human erythrocytes. While the presence of AMPs in T. serrulatus venom has been described in other works, this is the first work to characterize the presence of these molecules in the hemolymph (hemocytes) of this species and show its potential use as an alternative to conventional antibiotics against different species of microorganisms. Full article

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21 pages, 786 KiB

Open AccessEditor’s ChoiceReview

Updates on the Effect of Mycotoxins on Male Reproductive Efficiency in Mammals

by Diala El. Khoury, Salma Fayjaloun, Marc Nassar, Joseph Sahakian and Pauline Y. Aad

Toxins 2019, 11(9), 515; https://doi.org/10.3390/toxins11090515 - 3 Sep 2019

Cited by 42 | Viewed by 6585

Abstract

Mycotoxins are ubiquitous and unavoidable harmful fungal products with the ability to cause disease in both animals and humans, and are found in almost all types of foods, with a greater prevalence in hot humid environments. These mycotoxins vary greatly in structure and [...] Read more.

Mycotoxins are ubiquitous and unavoidable harmful fungal products with the ability to cause disease in both animals and humans, and are found in almost all types of foods, with a greater prevalence in hot humid environments. These mycotoxins vary greatly in structure and biochemical effects; therefore, by better understanding the toxicological and pathological aspects of mycotoxins, we can be better equipped to fight the diseases, as well as the biological and economic devastations, they induce. Multiple studies point to the association between a recent increase in male infertility and the increased occurrence of these mycotoxins in the environment. Furthermore, understanding how mycotoxins may induce an accumulation of epimutations during parental lifetimes can shed light on their implications with respect to fertility and reproductive efficiency. By acknowledging the diversity of mycotoxin molecular function and mode of action, this review aims to address the current limited knowledge on the effects of these chemicals on spermatogenesis and the various endocrine and epigenetics patterns associated with their disruptions. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure: Emerging Risks to Human Health)

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25 pages, 7424 KiB

Open AccessEditor’s ChoiceArticle

Comparative Structure–Activity Analysis of the Antimicrobial Activity, Cytotoxicity, and Mechanism of Action of the Fungal Cyclohexadepsipeptides Enniatins and Beauvericin

by Hamza Olleik, Cendrine Nicoletti, Mickael Lafond, Elise Courvoisier-Dezord, Peiwen Xue, Akram Hijazi, Elias Baydoun, Josette Perrier and Marc Maresca

Toxins 2019, 11(9), 514; https://doi.org/10.3390/toxins11090514 - 3 Sep 2019

Cited by 33 | Viewed by 4328

Abstract

Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these [...] Read more.

Filamentous fungi, although producing noxious molecules such as mycotoxins, have been used to produce numerous drugs active against human diseases such as paclitaxel, statins, and penicillin, saving millions of human lives. Cyclodepsipeptides are fungal molecules with potentially adverse and positive effects. Although these peptides are not novel, comparative studies of their antimicrobial activity, toxicity, and mechanism of action are still to be identified. In this study, the fungal cyclohexadepsipeptides enniatin (ENN) and beauvericin (BEA) were assessed to determine their antimicrobial activity and cytotoxicity against human cells. Results showed that these peptides were active against Gram-positive bacteria, Mycobacterium, and fungi, but not against Gram-negative bacteria. ENN and BEA had a limited hemolytic effect, yet were found to be toxic at low doses to nucleated human cells. Both peptides also interacted with bacterial lipids, causing low to no membrane permeabilization, but induced membrane depolarization and inhibition of macromolecules synthesis. The structure–activity analysis showed that the chemical nature of the side chains present on ENN and BEA (either iso-propyl, sec-butyl, or phenylmethyl) impacts their interaction with lipids, antimicrobial action, and toxicity. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 894 KiB

Open AccessEditor’s ChoiceArticle

Production of β-methylamino-L-alanine (BMAA) and Its Isomers by Freshwater Diatoms

by Jake P. Violi, Jordan A. Facey, Simon M. Mitrovic, Anne Colville and Kenneth J. Rodgers

Toxins 2019, 11(9), 512; https://doi.org/10.3390/toxins11090512 - 2 Sep 2019

Cited by 35 | Viewed by 5714

Abstract

β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with [...] Read more.

β-methylamino-L-alanine (BMAA) is a non-protein amino acid that has been implicated as a risk factor for motor neurone disease (MND). BMAA is produced by a wide range of cyanobacteria globally and by a small number of marine diatoms. BMAA is commonly found with two of its constitutional isomers: 2,4-diaminobutyric acid (2,4-DAB), and N-(2-aminoethyl)glycine (AEG). The isomer 2,4-DAB, like BMAA, has neurotoxic properties. While many studies have shown BMAA production by cyanobacteria, few studies have looked at other algal groups. Several studies have shown BMAA production by marine diatoms; however, there are no studies examining freshwater diatoms. This study aimed to determine if some freshwater diatoms produced BMAA, and which diatom taxa are capable of BMAA, 2,4-DAB and AEG production. Five axenic diatom cultures were established from river and lake sites across eastern Australia. Cultures were harvested during the stationary growth phase and intracellular amino acids were extracted. Using liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), diatom extracts were analysed for the presence of both free and protein-associated BMAA, 2,4-DAB and AEG. Of the five diatom cultures analysed, four were found to have detectable BMAA and AEG, while 2,4-DAB was found in all cultures. These results show that BMAA production by diatoms is not confined to marine genera and that the prevalence of these non-protein amino acids in Australian freshwater environments cannot be solely attributed to cyanobacteria. Full article

(This article belongs to the Special Issue Freshwater Cyanobacterial Toxins: Developments in Monitoring, Identification, Impacts and Factors Influencing Production)

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26 pages, 8963 KiB

Open AccessEditor’s ChoiceArticle

Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections

by Bruno Casciaro, Andrea Calcaterra, Floriana Cappiello, Mattia Mori, Maria Rosa Loffredo, Francesca Ghirga, Maria Luisa Mangoni, Bruno Botta and Deborah Quaglio

Toxins 2019, 11(9), 511; https://doi.org/10.3390/toxins11090511 - 1 Sep 2019

Cited by 39 | Viewed by 5018

Abstract

Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature [...] Read more.

Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

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20 pages, 1356 KiB

Open AccessEditor’s ChoiceReview

A Review of Cardiovascular Toxicity of Microcystins

by Linghui Cao, Isaac Yaw Massey, Hai Feng and Fei Yang

Toxins 2019, 11(9), 507; https://doi.org/10.3390/toxins11090507 - 30 Aug 2019

Cited by 45 | Viewed by 4876

Abstract

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products [...] Read more.

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products of cyanobacteria metabolism and the most harmful cyanotoxin found in water bodies. Recent studies provide strong evidence of positive associations between MC exposure and cardiotoxicity, representing a threat to human cardiovascular health. This review focuses on the effects of MCs on the cardiovascular system and provides some evidence that CVD could be induced by MCs. We summarized the current knowledge of the cardiovascular toxicity of MCs, with regard to direct cardiovascular toxicity and indirect cardiovascular toxicity. Toxicity of MCs is mainly governed by the increasing level of reactive oxygen species (ROS), oxidative stress in mitochondria and endoplasmic reticulum, the inhibition activities of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) and the destruction of cytoskeletons, which finally induce the occurrence of CVD. To protect human health from the threat of MCs, this paper also puts forward some directions for further research. Full article

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