Toxins

21 pages, 2821 KiB

Open AccessArticle

Seaweed Essential Oils as a New Source of Bioactive Compounds for Cyanobacteria Growth Control: Innovative Ecological Biocontrol Approach

by Soukaina El Amrani Zerrifi, Fatima El Khalloufi, Richard Mugani, Redouane El Mahdi, Ayoub Kasrati, Bouchra Soulaimani, Lillian Barros, Isabel C. F. R. Ferreira, Joana S. Amaral, Tiane Cristine Finimundy, Abdelaziz Abbad, Brahim Oudra, Alexandre Campos and Vitor Vasconcelos

Toxins 2020, 12(8), 527; https://doi.org/10.3390/toxins12080527 - 17 Aug 2020

Cited by 13 | Viewed by 4961

Abstract

The application of natural compounds extracted from seaweeds is a promising eco-friendly alternative solution for harmful algae control in aquatic ecosystems. In the present study, the anti-cyanobacterial activity of three Moroccan marine macroalgae essential oils (EOs) was tested and evaluated on unicellular Microcystis [...] Read more.

The application of natural compounds extracted from seaweeds is a promising eco-friendly alternative solution for harmful algae control in aquatic ecosystems. In the present study, the anti-cyanobacterial activity of three Moroccan marine macroalgae essential oils (EOs) was tested and evaluated on unicellular Microcystis aeruginosa cyanobacterium. Additionally, the possible anti-cyanobacterial response mechanisms were investigated by analyzing the antioxidant enzyme activities of M. aeruginosa cells. The results of EOs GC–MS analyses revealed a complex chemical composition, allowing the identification of 91 constituents. Palmitic acid, palmitoleic acid, and eicosapentaenoic acid were the most predominant compounds in Cystoseira tamariscifolia, Sargassum muticum, and Ulva lactuca EOs, respectively. The highest anti-cyanobacterial activity was recorded for Cystoseira tamariscifolia EO (ZI = 46.33 mm, MIC = 7.81 μg mL⁻¹, and MBC = 15.62 μg mL⁻¹). The growth, chlorophyll-a and protein content of the tested cyanobacteria were significantly reduced by C. tamariscifolia EO at both used concentrations (inhibition rate >67% during the 6 days test period in liquid media). Furthermore, oxidative stress caused by C. tamariscifolia EO on cyanobacterium cells showed an increase of the activities of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) concentration was significantly elevated after 2 days of exposure. Overall, these experimental findings can open a promising new natural pathway based on the use of seaweed essential oils to the fight against potent toxic harmful cyanobacterial blooms (HCBs). Full article

(This article belongs to the Special Issue Removal of Cyanobacteria and Cyanotoxins in Waters)

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17 pages, 819 KiB

Open AccessArticle

Identification and Structure Elucidation of Epoxyjanthitrems from Lolium perenne Infected with the Endophytic Fungus Epichloë festucae var. lolii and Determination of the Tremorgenic and Anti-Insect Activity of Epoxyjanthitrem I

by Sarah C. Finch, Michèle R. Prinsep, Alison J. Popay, Alistair L. Wilkins, Nicola G. Webb, Sweta Bhattarai, Joanne G. Jensen, Allan D. Hawkes, Jacob V. Babu, Brian A. Tapper and Geoffrey A. Lane

Toxins 2020, 12(8), 526; https://doi.org/10.3390/toxins12080526 - 17 Aug 2020

Cited by 16 | Viewed by 2785

Abstract

Epoxyjanthitrems I–IV (1–4) and epoxyjanthitriol (5) were isolated from seed of perennial ryegrass (Lolium perenne) infected with the endophytic fungus Epichloë festucae var. lolii. Although structures for epoxyjanthitrems I–IV have previously been proposed in the [...] Read more.

Epoxyjanthitrems I–IV (1–4) and epoxyjanthitriol (5) were isolated from seed of perennial ryegrass (Lolium perenne) infected with the endophytic fungus Epichloë festucae var. lolii. Although structures for epoxyjanthitrems I–IV have previously been proposed in the literature, this is the first report of a full structural elucidation yielding NMR (Nuclear magnetic resonance) assignments for all five epoxyjanthitrem compounds, and additionally, it is the first isolation of epoxyjanthitriol (5). Epoxyjanthitrem I induced tremors in mice and gave a dose dependent reduction in weight gain and feeding for porina (Wiseana cervinata), a common pasture pest in New Zealand. These data suggest that epoxyjanthitrems are involved in the observed effects of the AR37 endophyte on livestock and insect pests. Full article

(This article belongs to the Special Issue Identification and Functional Characterization of Plant Toxins)

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18 pages, 17480 KiB

Open AccessArticle

Zearalenone and Metabolites in Livers of Turkey Poults and Broiler Chickens Fed with Diets Containing Fusariotoxins

by Didier Tardieu, Angelique Travel, Jean-Paul Metayer, Celeste Le Bourhis and Philippe Guerre

Toxins 2020, 12(8), 525; https://doi.org/10.3390/toxins12080525 - 15 Aug 2020

Cited by 7 | Viewed by 2657

Abstract

Zearalenone (ZEN) and metabolites were measured in livers of turkeys and broilers fed a control diet free of mycotoxins, a diet that contained 0.5 mg/kg ZEN (ZEN diet), and a diet that contained 0.5, 5, and 20 mg/kg of ZEN, fumonisins, and deoxynivalenol, [...] Read more.

Zearalenone (ZEN) and metabolites were measured in livers of turkeys and broilers fed a control diet free of mycotoxins, a diet that contained 0.5 mg/kg ZEN (ZEN diet), and a diet that contained 0.5, 5, and 20 mg/kg of ZEN, fumonisins, and deoxynivalenol, respectively (ZENDONFB diet). The feed was individually distributed to male Grade Maker turkeys from the 55th to the 70th day of age and to male Ross chickens from the 1st to the 35th day of age, without any signs of toxicity. Together, the free and conjugated forms of ZEN, α- and β-zearalenols (ZOLs), zearalanone (ZAN), and α- and β-zearalanols (ZALs) were measured by UHPLC-MS/MS with [¹³C₁₈]-ZEN as an internal standard and immunoaffinity clean-up of samples. ZAN and ZALs were not detected. ZEN and ZOLs were mainly found in their conjugated forms. α-ZOL was the most abundant and was found at a mean concentration of 2.23 and 1.56 ng/g in turkeys and chickens, respectively. Consuming the ZENDONFB diet significantly increased the level of total metabolites in the livers of chickens. Furthermore, this increase was more pronounced for the free forms of α-ZOL than for the conjugated forms. An investigation of the presence of ZEN and metabolites in muscle with the methods validated for the liver failed to reveal any traces of these contaminants in this tissue. These results suggest that concomitant dietary exposure to deoxynivalenol (DON) and fumonisins (FB) may alter the metabolism and persistence of ZEN and its metabolites in the liver. Full article

(This article belongs to the Section Mycotoxins)

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13 pages, 2370 KiB

Open AccessArticle

Antiviral Activity of PD-L1 and PD-L4, Type 1 Ribosome Inactivating Proteins from Leaves of Phytolacca dioica L. in the Pathosystem Phaseolus vulgaris–Tobacco Necrosis Virus (TNV)

by Daniela Bulgari, Nicola Landi, Sara Ragucci, Franco Faoro and Antimo Di Maro

Toxins 2020, 12(8), 524; https://doi.org/10.3390/toxins12080524 - 14 Aug 2020

Cited by 8 | Viewed by 2781

Abstract

Using the pathosystem Phaseolus vulgaris–tobacco necrosis virus (TNV), we demonstrated that PD-L1 and PD-L4, type-1 ribosome inactivating proteins (RIPs) from leaves of Phytolacca dioica L., possess a strong antiviral activity. This activity was exerted both when the RIPs and the virus were [...] Read more.

Using the pathosystem Phaseolus vulgaris–tobacco necrosis virus (TNV), we demonstrated that PD-L1 and PD-L4, type-1 ribosome inactivating proteins (RIPs) from leaves of Phytolacca dioica L., possess a strong antiviral activity. This activity was exerted both when the RIPs and the virus were inoculated together in the same leaf and when they were inoculated or applied separately in the adaxial and abaxial leaf surfaces. This suggests that virus inhibition would mainly occur inside plant cells at the onset of infection. Histochemical studies showed that both PD-L1 and PD-L4 were not able to induce oxidative burst and cell death in treated leaves, which were instead elicited by inoculation of the virus alone. Furthermore, when RIPs and TNV were inoculated together, no sign of H₂O₂ deposits and cell death were detectable, indicating that the virus could have been inactivated in a very early stage of infection, before the elicitation of a hypersensitivity reaction. In conclusion, the strong antiviral activity is likely exerted inside host cells as soon the virus disassembles to start translation of the viral genome. This activity is likely directed towards both viral and ribosomal RNA, explaining the almost complete abolition of infection when virus and RIP enter together into the cells. Full article

(This article belongs to the Special Issue Biological Activities of Ribosome-Inactivating Proteins)

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17 pages, 1287 KiB

Open AccessArticle

Bioaccumulation and Phytotoxicity and Human Health Risk from Microcystin-LR under Various Treatments: A Pot Study

by Lei Xiang, Yan-Wen Li, Zhen-Ru Wang, Bai-Lin Liu, Hai-Ming Zhao, Hui Li, Quan-Ying Cai, Ce-Hui Mo and Qing X. Li

Toxins 2020, 12(8), 523; https://doi.org/10.3390/toxins12080523 - 14 Aug 2020

Cited by 17 | Viewed by 3305

Abstract

Microcystin-LR (MC-LR) is prevalent in water and can be translocated into soil-crop ecosystem via irrigation, overflow (pollution accident), and cyanobacterial manure applications, threatening agricultural production and human health. However, the effects of various input pathways on the bioaccumulation and toxicity of MCs in [...] Read more.

Microcystin-LR (MC-LR) is prevalent in water and can be translocated into soil-crop ecosystem via irrigation, overflow (pollution accident), and cyanobacterial manure applications, threatening agricultural production and human health. However, the effects of various input pathways on the bioaccumulation and toxicity of MCs in terrestrial plants have been hardly reported so far. In the present study, pot experiments were performed to compare the bioaccumulation, toxicity, and health risk of MC-LR as well as its degradation in soils among various treatments with the same total amount of added MC-LR (150 μg/kg). The treatments included irrigation with polluted water (IPW), cultivation with polluted soil (CPS), and application of cyanobacterial manure (ACM). Three common leaf-vegetables in southern China were used in the pot experiments, including Ipomoea batatas L., Brassica juncea L., and Brassica alboglabra L. All leaf vegetables could bioaccumulate MC-LR under the three treatments, with much higher MC-LR bioaccumulation, especially root bioconcentration observed in ACM treatment than IPW and CPS treatments. An opposite trend in MC-LR degradation in soils of these treatments indicated that ACM could limit MC-LR degradation in soils and thus promote its bioaccumulation in the vegetables. MC-LR bioaccumulation could cause toxicity to the vegetables, with the highest toxic effects observed in ACM treatment. Similarly, bioaccumulation of MC-LR in the edible parts of the leaf-vegetables posed 1.1~4.8 fold higher human health risks in ACM treatment than in IPW and CPS treatments. The findings of this study highlighted a great concern on applications of cyanobacterial manure. Full article

(This article belongs to the Special Issue Health Risk Assessment Related to Cyanotoxins Exposure)

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24 pages, 1237 KiB

Open AccessEditor’s ChoiceReview

Current Insights on Vegetative Insecticidal Proteins (Vip) as Next Generation Pest Killers

by Tahira Syed, Muhammad Askari, Zhigang Meng, Yanyan Li, Muhammad Ali Abid, Yunxiao Wei, Sandui Guo, Chengzhen Liang and Rui Zhang

Toxins 2020, 12(8), 522; https://doi.org/10.3390/toxins12080522 - 14 Aug 2020

Cited by 34 | Viewed by 6411 | Correction

Abstract

Bacillus thuringiensis (Bt) is a gram negative soil bacterium. This bacterium secretes various proteins during different growth phases with an insecticidal potential against many economically important crop pests. One of the important families of Bt proteins is vegetative insecticidal proteins (Vip), which are [...] Read more.

Bacillus thuringiensis (Bt) is a gram negative soil bacterium. This bacterium secretes various proteins during different growth phases with an insecticidal potential against many economically important crop pests. One of the important families of Bt proteins is vegetative insecticidal proteins (Vip), which are secreted into the growth medium during vegetative growth. There are three subfamilies of Vip proteins. Vip1 and Vip2 heterodimer toxins have an insecticidal activity against many Coleopteran and Hemipteran pests. Vip3, the most extensively studied family of Vip toxins, is effective against Lepidopteron. Vip proteins do not share homology in sequence and binding sites with Cry proteins, but share similarities at some points in their mechanism of action. Vip3 proteins are expressed as pyramids alongside Cry proteins in crops like maize and cotton, so as to control resistant pests and delay the evolution of resistance. Biotechnological- and in silico-based analyses are promising for the generation of mutant Vip proteins with an enhanced insecticidal activity and broader spectrum of target insects. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

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12 pages, 2516 KiB

Open AccessArticle

Contamination of Zearalenone from China in 2019 by a Visual and Digitized Immunochromatographic Assay

by Xia Hong, Yuhao Mao, Chuqin Yang, Zhenjiang Liu, Ming Li and Daolin Du

Toxins 2020, 12(8), 521; https://doi.org/10.3390/toxins12080521 - 14 Aug 2020

Cited by 17 | Viewed by 2911

Abstract

Zearalenone (ZEN) is a prevalent mycotoxin that needs intensive monitoring. A semi-quantitative and quantitative immunochromatographic assay (ICA) was assembled for investigating ZEN contamination in 187 samples of cereal and their products from China in 2019. The semi-quantitative detection model had a limit of [...] Read more.

Zearalenone (ZEN) is a prevalent mycotoxin that needs intensive monitoring. A semi-quantitative and quantitative immunochromatographic assay (ICA) was assembled for investigating ZEN contamination in 187 samples of cereal and their products from China in 2019. The semi-quantitative detection model had a limit of detection (LOD) of 0.50 ng/mL with visual judgment and could be completely inhibited within 5 min at 3.0 ng/mL ZEN. The quantitative detection model had a lower LOD of 0.25 ng/mL, and ZEN could be accurately and digitally detected from 0.25–4.0 ng/mL. The ICA method had a high sensitivity, specificity, and accuracy for on-site ZEN detection. For investigation of the authentic samples, the ZEN-positive rate was 62.6%, and the ZEN-positive levels ranged from 2.7 to 867.0 ng/g, with an average ZEN-positive level being 85.0 ng/g. Of the ZEN-positive samples, 6.0% exceeded the values of the limit levels. The ZEN-positive samples were confirmed to be highly correlated using LC-MS/MS (R² = 0.9794). This study could provide an efficiency and accuracy approach for ZEN in order to achieve visual and digitized on-site investigation. This significant information about the ZEN contamination levels might contribute to monitoring mycotoxin occurrence and for ensuring food safety. Full article

(This article belongs to the Special Issue Rapid Detection of Mycotoxin Contamination)

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11 pages, 897 KiB

Open AccessArticle

Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta

by Ottilie Katali, Loide Shipingana, Peter Nyarangó, Mirva Pääkkönen, Erastus Haindongo, Timothy Rennie, Peter James, John Eriksson and Christian John Hunter

Toxins 2020, 12(8), 520; https://doi.org/10.3390/toxins12080520 - 14 Aug 2020

Cited by 7 | Viewed by 4218

Abstract

Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. [...] Read more.

Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA₂) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation. Full article

(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)

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15 pages, 2499 KiB

Open AccessArticle

Production of Recombinant Gelonin Using an Automated Liquid Chromatography System

by Maria E. B. Berstad, Lawrence H. Cheung and Anette Weyergang

Toxins 2020, 12(8), 519; https://doi.org/10.3390/toxins12080519 - 13 Aug 2020

Cited by 1 | Viewed by 2949

Abstract

Advances in recombinant DNA technology have opened up new possibilities of exploiting toxic proteins for therapeutic purposes. Bringing forth these protein toxins from the bench to the bedside strongly depends on the availability of production methods that are reproducible, scalable and comply with [...] Read more.

Advances in recombinant DNA technology have opened up new possibilities of exploiting toxic proteins for therapeutic purposes. Bringing forth these protein toxins from the bench to the bedside strongly depends on the availability of production methods that are reproducible, scalable and comply with good manufacturing practice (GMP). The type I ribosome-inhibiting protein, gelonin, has great potential as an anticancer drug, but is sequestrated in endosomes and lysosomes. This can be overcome by combination with photochemical internalization (PCI), a method for endosomal drug release. The combination of gelonin-based drugs and PCI represents a tumor-targeted therapy with high precision and efficiency. The aim of this study was to produce recombinant gelonin (rGel) at high purity and quantity using an automated liquid chromatography system. The expression and purification process was documented as highly efficient (4.4 mg gelonin per litre induced culture) and reproducible with minimal loss of target protein (~50% overall yield compared to after initial immobilized metal affinity chromatography (IMAC)). The endotoxin level of 0.05–0.09 EU/mg was compatible with current standards for parenteral drug administration. The automated system provided a consistent output with minimal human intervention and close monitoring of each purification step enabled optimization of both yield and purity of the product. rGel was shown to have equivalent biological activity and cytotoxicity, both with and without PCI-mediated delivery, as rGel_ref produced without an automated system. This study presents a highly refined and automated manufacturing procedure for recombinant gelonin at a quantity and quality sufficient for preclinical evaluation. The methods established in this report are in compliance with high quality standards and compose a solid platform for preclinical development of gelonin-based drugs. Full article

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

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14 pages, 4574 KiB

Open AccessArticle

The Proposed Neurotoxin β-N-Methylamino-l-Alanine (BMAA) Is Taken up through Amino-Acid Transport Systems in the Cyanobacterium Anabaena PCC 7120

by Zi-Qian Wang, Suqin Wang, Ju-Yuan Zhang, Gui-Ming Lin, Nanqin Gan, Lirong Song, Xiaoli Zeng and Cheng-Cai Zhang

Toxins 2020, 12(8), 518; https://doi.org/10.3390/toxins12080518 - 13 Aug 2020

Cited by 8 | Viewed by 2797

Abstract

Produced by cyanobacteria and some plants, BMAA is considered as an important environmental factor in the occurrence of some neurodegenerative diseases. Neither the underlying mechanism of its toxicity, nor its biosynthetic or metabolic pathway in cyanobacteria is understood. Interestingly, BMAA is found to [...] Read more.

Produced by cyanobacteria and some plants, BMAA is considered as an important environmental factor in the occurrence of some neurodegenerative diseases. Neither the underlying mechanism of its toxicity, nor its biosynthetic or metabolic pathway in cyanobacteria is understood. Interestingly, BMAA is found to be toxic to some cyanobacteria, making it possible to dissect the mechanism of BMAA metabolism by genetic approaches using these organisms. In this study, we used the cyanobacterium Anabaena PCC 7120 to isolate BMAA-resistant mutants. Following genomic sequencing, several mutations were mapped to two genes involved in amino acids transport, suggesting that BMAA was taken up through amino acid transporters. This conclusion was supported by the protective effect of several amino acids against BMAA toxicity. Furthermore, targeted inactivation of genes encoding different amino acid transport pathways conferred various levels of resistance to BMAA. One mutant inactivating all three major amino acid transport systems could no longer take up BMAA and gained full resistance to BMAA toxicity. Therefore, BMAA is a substrate of amino acid transporters, and cyanobacteria are interesting models for genetic analysis of BMAA transport and metabolism. Full article

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

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16 pages, 1859 KiB

Open AccessArticle

Varying Protein Levels Influence Metabolomics and the Gut Microbiome in Healthy Adult Dogs

by Eden Ephraim, Chun-Yen Cochrane and Dennis E. Jewell

Toxins 2020, 12(8), 517; https://doi.org/10.3390/toxins12080517 - 12 Aug 2020

Cited by 31 | Viewed by 5386

Abstract

The optimal ranges of protein for healthy adult dogs are not known. This study evaluated the impact of long-term consumption of foods containing low, medium, and high levels of protein on serum, urine, and fecal metabolites, and gut microbiome in beagles. Following maintenance [...] Read more.

The optimal ranges of protein for healthy adult dogs are not known. This study evaluated the impact of long-term consumption of foods containing low, medium, and high levels of protein on serum, urine, and fecal metabolites, and gut microbiome in beagles. Following maintenance on a prefeed food for 14 days, dogs (15 neutered males, 15 spayed females, aged 2–9 years, mean initial weight 11.3 kg) consumed the low (18.99%, dry matter basis), medium (25.34%), or high (45.77%) protein foods, each for 90 days, in a William’s Latin Square Design sequence. In serum and/or urine, metabolites associated with inflammation (9,10-dihydroxyoctadecanoic acid (DiHOME)), 12,13-DiHOME) and kidney dysfunction (urea, 5-hydroxyindole sulfate, 7-hydroxyindole sulfate, p-cresol sulfate) increased with higher protein levels in food, while one-carbon pathway metabolites (betaine, dimethylglycine, sarcosine) decreased. Fecal pH increased with protein consumed, and levels of beneficial indoles and short-chain fatty acids decreased while branched-chain fatty acids increased. Beta diversity of the fecal microbiome was significantly different, with increased abundances of proteolytic bacteria with higher protein food. Feeding dogs a high amount of protein leads to a shift to proteolytic gut bacteria, higher fecal pH, and is associated with increased levels of metabolites linked with inflammation and kidney dysfunction. Full article

(This article belongs to the Special Issue New Strategies for the Reduction of Uremic Toxins)

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22 pages, 1222 KiB

Open AccessReview

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

by Casey E. Butrico and James E. Cassat

Toxins 2020, 12(8), 516; https://doi.org/10.3390/toxins12080516 - 12 Aug 2020

Cited by 31 | Viewed by 7134

Abstract

Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction [...] Read more.

Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, S. aureus forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator (agr) locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host. Moreover, the Agr system is subject to complex crosstalk with other S. aureus regulatory systems, including SaeRS and SrrAB, which can significantly impact the progression of osteomyelitis. The objective of this review is to highlight Agr regulation, its implications on toxin production, factors that affect Agr activation, and the potential paradoxical influences of Agr regulation on disease progression during osteomyelitis. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins: Promoter or Handicap during Infection)

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15 pages, 3004 KiB

Open AccessArticle

The Influence of NaCl and Glucose Content on Growth and Ochratoxin A Production by Aspergillus ochraceus, Aspergillus carbonarius and Penicillium nordicum

by Yan Wang, Hao Yan, Jing Neng, Jian Gao, Bolei Yang and Yang Liu

Toxins 2020, 12(8), 515; https://doi.org/10.3390/toxins12080515 - 12 Aug 2020

Cited by 17 | Viewed by 3418

Abstract

Ochratoxin A (OTA) is a nephrotoxic mycotoxin, which deserves particular attention for its widespread contamination of a variety of food and feed. Aspergillus ochraceus, Aspergillus carbonarius, and Penicillium nordicum are an important source of OTA in three different kinds of food [...] Read more.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin, which deserves particular attention for its widespread contamination of a variety of food and feed. Aspergillus ochraceus, Aspergillus carbonarius, and Penicillium nordicum are an important source of OTA in three different kinds of food commodities, including cereals, grape and dried fruit products, and dry-cured meat products. Deeper knowledge of OTA production and mycelium growth related to the high-sugar or NaCl-rich environments was gained in this manuscript. A. ochraceus and P. nordicum were likely to have greater growth rates in medium supplied with certain concentrations of NaCl (0–80 g/L), and the colony diameter was the largest at the salt content of 40 g/L. P. nordicum was more suitable to grow in NaCl-riched medium, the OTA production was increased to 316 ppb from 77 ppb when 20 g/L NaCl was added. The capability of OTA production was inhibited when salt content was 40 g/L and 60 g/L in A. ochraceus and P. nordicum, respectively. As the glucose content increased to 250 g/L, the capacity of mycelium growth and sporulation was increased significantly in A. ochraceus and A. carbonarius. A. carbonarius was more suitable to grow in high-sugar grape products. OTA production was significantly promoted with an added 100 g/L glucose in A. carbonarius. OTA production was inhibited when glucose content was 150 g/L and in 200 g/L in A. ochraceus and A. carbonarius, respectively. NaCl and glucose have an effect on fungal growth and OTA production, and the activation of biosynthetic genes of OtaA. These results would allow designing new strategies to prevent OTA accumulation on sugar or NaCl-riched foodstuffs and achieve the objective to manufacture cereals, dried vine fruits and dry-cured ham, free of OTA. Full article

(This article belongs to the Collection Ochratoxins-Collection)

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17 pages, 1077 KiB

Open AccessReview

The Tripartite Interaction of Host Immunity–Bacillus thuringiensis Infection–Gut Microbiota

by Shuzhong Li, Surajit De Mandal, Xiaoxia Xu and Fengliang Jin

Toxins 2020, 12(8), 514; https://doi.org/10.3390/toxins12080514 - 12 Aug 2020

Cited by 27 | Viewed by 4828

Abstract

Bacillus thuringiensis (Bt) is an important cosmopolitan bacterial entomopathogen, which produces various protein toxins that have been expressed in transgenic crops. The evolved molecular interaction between the insect immune system and gut microbiota is changed during the Bt infection process. The host immune [...] Read more.

Bacillus thuringiensis (Bt) is an important cosmopolitan bacterial entomopathogen, which produces various protein toxins that have been expressed in transgenic crops. The evolved molecular interaction between the insect immune system and gut microbiota is changed during the Bt infection process. The host immune response, such as the expression of induced antimicrobial peptides (AMPs), the melanization response, and the production of reactive oxygen species (ROS), varies with different doses of Bt infection. Moreover, B. thuringiensis infection changes the abundance and structural composition of the intestinal bacteria community. The activated immune response, together with dysbiosis of the gut microbiota, also has an important effect on Bt pathogenicity and insect resistance to Bt. In this review, we attempt to clarify this tripartite interaction of host immunity, Bt infection, and gut microbiota, especially the important role of key immune regulators and symbiotic bacteria in the Bt killing activity. Increasing the effectiveness of biocontrol agents by interfering with insect resistance and controlling symbiotic bacteria can be important steps for the successful application of microbial biopesticides. Full article

(This article belongs to the Special Issue Bacillus thuringiensis Toxins: Functional Characterization and Mechanism of Action)

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12 pages, 450 KiB

Open AccessReview

Occupational Exposure to Mycotoxins—Different Sampling Strategies Telling a Common Story Regarding Occupational Studies Performed in Portugal (2012–2020)

by Susana Viegas, Carla Viegas, Carla Martins and Ricardo Assunção

Toxins 2020, 12(8), 513; https://doi.org/10.3390/toxins12080513 - 11 Aug 2020

Cited by 14 | Viewed by 3289

Abstract

In occupational settings where exposure to organic dust occurs (e.g., intensive animal production, waste management, farming and many others) workers can also be exposed to mycotoxins. However, recognizing exposure to mycotoxins in workplace environments does not happen commonly and, consequently, remains as a [...] Read more.

In occupational settings where exposure to organic dust occurs (e.g., intensive animal production, waste management, farming and many others) workers can also be exposed to mycotoxins. However, recognizing exposure to mycotoxins in workplace environments does not happen commonly and, consequently, remains as a not identified occupational risk factor. In the last decade, work developed in different occupational settings, using different sampling approaches reported that occupational exposure to mycotoxins occurs and it’s of upmost importance to be seen as an occupational concern that needs to be tackled. This paper intends to discuss the several possibilities available for assessing and characterizing the occupational exposure to mycotoxins through the description of the advantages and limitations of the different sampling strategies. Overviewing the approaches and the main achievements used in several field campaigns developed in Portugal, the knowledge obtained will be used to support the identification of the main aspects to consider when designing new occupational studies. The need for additional research work will also be discussed where new directions to follow will be debated. Full article

(This article belongs to the Special Issue Occupational Exposure to Mycotoxins—Challenges and Ways Forward)

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12 pages, 2813 KiB

Open AccessArticle

Survey of Tetrodotoxin in New Zealand Bivalve Molluscan Shellfish over a 16-Month Period

by Michael J. Boundy, Laura Biessy, Brian Roughan, Jeane Nicolas and D. Tim Harwood

Toxins 2020, 12(8), 512; https://doi.org/10.3390/toxins12080512 - 10 Aug 2020

Cited by 12 | Viewed by 3319

Abstract

Tetrodotoxin (TTX) is a heat-stable neurotoxin typically associated with pufferfish intoxications. It has also been detected in shellfish from Japan, the United Kingdom, Greece, China, Italy, the Netherlands and New Zealand. A recent European Food Safety Authority (EFSA) scientific opinion concluded that a [...] Read more.

Tetrodotoxin (TTX) is a heat-stable neurotoxin typically associated with pufferfish intoxications. It has also been detected in shellfish from Japan, the United Kingdom, Greece, China, Italy, the Netherlands and New Zealand. A recent European Food Safety Authority (EFSA) scientific opinion concluded that a level of <0.044 mg TTX/kg in marine bivalves and gastropods, based on a 400 g portion size, does not result in adverse effects in humans. There have been no reports of human illness attributed to the consumption of New Zealand shellfish containing TTX. To obtain a greater understanding of its presence, a survey of non-commercial New Zealand shellfish was performed between December 2016 and March 2018. During this period, 766 samples were analysed from 8 different species. TTX levels were found to be low and similar to those observed in shellfish from other countries, except for pipi (Paphies australis), a clam species endemic to New Zealand. All pipi analysed as part of the survey were found to contain detectable levels of TTX, and pipi from a sampling site in Hokianga Harbour contained consistently elevated levels. In contrast, no TTX was observed in cockles from this same sampling site. No recreationally harvested shellfish species, including mussels, oysters, clams and tuatua, contained TTX levels above the recommended EFSA safe guidance level. The levels observed in shellfish were considerably lower than those reported in other marine organisms known to contain TTX and cause human intoxication (e.g., pufferfish). Despite significant effort, the source of TTX in shellfish, and indeed all animals, remains unresolved making it a difficult issue to understand and manage. Full article

(This article belongs to the Special Issue Analysis and Evaluation of Tetrodotoxin)

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20 pages, 1388 KiB

Open AccessArticle

Safety, Tolerability, Pharmacokinetics, and Concentration-QTc Analysis of Tetrodotoxin: A Randomized, Dose Escalation Study in Healthy Adults

by Mojgan Kavoosi, Terry E. O’Reilly, Mehran Kavoosi, Peng Chai, Caroline Engel, Walter Korz, Christopher C. Gallen and Robert M. Lester

Toxins 2020, 12(8), 511; https://doi.org/10.3390/toxins12080511 - 09 Aug 2020

Cited by 9 | Viewed by 5408

Abstract

Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. [...] Read more.

Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 µg, 30 µg, and 45 µg TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (C_max) within 1.5 h. Both extent of exposure (AUC) and C_max increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (ΔΔQTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence ≥5%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity. Full article

(This article belongs to the Special Issue Tetrodotoxin (TTX) as a Therapeutic Agent)

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14 pages, 6078 KiB

Open AccessArticle

A Role of Newly Found Auxiliary Site in Phospholipase A₁ from Thai Banded Tiger Wasp (Vespa affinis) in Its Enzymatic Enhancement: In Silico Homology Modeling and Molecular Dynamics Insights

by Withan Teajaroen, Suphaporn Phimwapi, Jureerut Daduang, Sompong Klaynongsruang, Varomyalin Tipmanee and Sakda Daduang

Toxins 2020, 12(8), 510; https://doi.org/10.3390/toxins12080510 - 08 Aug 2020

Cited by 8 | Viewed by 3090

Abstract

Phospholipase A₁ from Thai banded tiger wasp (Vespa affinis) venom also known as Ves a 1 plays an essential role in fatal vespid allergy. Ves a 1 becomes an important therapeutic target for toxin remedy. However, established Ves a 1 structure or [...] Read more.

Phospholipase A₁ from Thai banded tiger wasp (Vespa affinis) venom also known as Ves a 1 plays an essential role in fatal vespid allergy. Ves a 1 becomes an important therapeutic target for toxin remedy. However, established Ves a 1 structure or a mechanism of Ves a 1 function were not well documented. This circumstance has prevented efficient design of a potential phospholipase A₁ inhibitor. In our study, we successfully recruited homology modeling and molecular dynamic (MD) simulation to model Ves a 1 three-dimensional structure. The Ves a 1 structure along with dynamic behaviors were visualized and explained. In addition, we performed molecular docking of Ves a 1 with 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) lipid to assess a possible lipid binding site. Interestingly, molecular docking predicted another lipid binding region apart from its corresponding catalytic site, suggesting an auxiliary role of the alternative site at the Ves a 1 surface. The new molecular mechanism related to the surface lipid binding site (auxiliary site) provided better understanding of how phospholipase A₁ structure facilitates its enzymatic function. This auxiliary site, conserved among Hymenoptera species as well as some mammalian lipases, could be a guide for interaction-based design of a novel phospholipase A₁ inhibitor. Full article

(This article belongs to the Special Issue Application of Venom Phospholipase in the Treatment of Diseases)

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17 pages, 331 KiB

Open AccessReview

Foodborne Botulism: Clinical Diagnosis and Medical Treatment

by Davide Lonati, Azzurra Schicchi, Marta Crevani, Eleonora Buscaglia, Giulia Scaravaggi, Francesca Maida, Marco Cirronis, Valeria Margherita Petrolini and Carlo Alessandro Locatelli

Toxins 2020, 12(8), 509; https://doi.org/10.3390/toxins12080509 - 07 Aug 2020

Cited by 41 | Viewed by 12343

Abstract

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All [...] Read more.

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain–Barré syndrome—Miller–Fisher variant, Eaton–Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure. Full article

(This article belongs to the Special Issue New Challenges in Foodborne Botulism Outbreaks)

16 pages, 3221 KiB

Open AccessArticle

Purification and Characterization of the Pink-Floyd Drillipeptide, a Bioactive Venom Peptide from Clavus davidgilmouri (Gastropoda: Conoidea: Drilliidae)

by Victor M. Chua, Joanna Gajewiak, Maren Watkins, Samuel S. Espino, Iris Bea L. Ramiro, Carla A. Omaga, Julita S. Imperial, Louie Paolo D. Carpio, Alexander Fedosov, Helena Safavi-Hemami, Lilibeth A. Salvador-Reyes, Baldomero M. Olivera and Gisela P. Concepcion

Toxins 2020, 12(8), 508; https://doi.org/10.3390/toxins12080508 - 07 Aug 2020

Cited by 1 | Viewed by 3592

Abstract

The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly [...] Read more.

The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly diversified family in Conoidea, have not previously been investigated. In this report, we provide the first biochemical characterization of a component in a Drilliidae venom and define a gene superfamily of venom peptides. A bioactive peptide, cdg14a, was purified from the venom of Clavus davidgilmouri Fedosov and Puillandre, 2020. The peptide is small (23 amino acids), disulfide-rich (4 cysteine residues) and belongs to the J-like drillipeptide gene superfamily. Other members of this superfamily share a conserved signal sequence and the same arrangement of cysteine residues in their predicted mature peptide sequences. The cdg14a peptide was chemically synthesized in its bioactive form. It elicited scratching and hyperactivity, followed by a paw-thumping phenotype in mice. Using the Constellation Pharmacology platform, the cdg14a drillipeptide was shown to cause increased excitability in a majority of non-peptidergic nociceptors, but did not affect other subclasses of dorsal root ganglion (DRG) neurons. This suggests that the cdg14a drillipeptide may be blocking a specific molecular isoform of potassium channels. The potency and selectivity of this biochemically characterized drillipeptide suggest that the venoms of the Drilliidae are a rich source of novel and selective ligands for ion channels and other important signaling molecules in the nervous system. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 306 KiB

Open AccessArticle

Adverse Reactions after Administration of Antivenom in Korea

by Jin Seok Shim, Hyunggoo Kang, Yongil Cho, Hyungoo Shin and Heekyung Lee

Toxins 2020, 12(8), 507; https://doi.org/10.3390/toxins12080507 - 06 Aug 2020

Cited by 13 | Viewed by 3832

Abstract

Kovax^® antivenom is the main treatment for toxins produced by the Gloydius species. However, research on adverse reactions after Kovax^® antivenom administration is scarce. We aimed to identify the incidence and characteristics of adverse reactions after Kovax^® antivenom administration. We [...] Read more.

Kovax^® antivenom is the main treatment for toxins produced by the Gloydius species. However, research on adverse reactions after Kovax^® antivenom administration is scarce. We aimed to identify the incidence and characteristics of adverse reactions after Kovax^® antivenom administration. We conducted a retrospective review of the medical records of snakebite patients in Korea between January 2008 and September 2019. We identified the frequency, characteristics, and treatments of adverse reactions to Kovax^® antivenom. There were 150 patients with snakebites, of whom 121 (80.7%) patients received Kovax^® antivenom. Adverse reactions occurred in five patients (4.1%). Acute adverse reactions within 24 h of antivenom administration occurred in two patients (1.7%). The symptoms of patients with acute adverse reactions were nausea, diaphoresis, dizziness, and hypotension. Delayed adverse reactions that occurred 24 h after antivenom administration were reported in three patients (2.5%). One patient had a skin rash after 10 days, and two patients had fever 37 and 48 h after antivenom use. In conclusion, most patients were managed safely after Kovax^® antivenom, and the incidence of adverse reactions was low. Severe adverse reactions occurred in a small percentage of patients, and there were no deaths. Full article

(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)

11 pages, 4490 KiB

Open AccessArticle

Endothelial Cell-Specific Molecule 1 Promotes Endothelial to Mesenchymal Transition in Renal Fibrosis

by Tung-Wei Hung, Chao-Yang Chu, Chen-Lin Yu, Chu-Che Lee, Li-Sung Hsu, Yong-Syuan Chen, Yi-Hsien Hsieh and Jen-Pi Tsai

Toxins 2020, 12(8), 506; https://doi.org/10.3390/toxins12080506 - 06 Aug 2020

Cited by 12 | Viewed by 3181

Abstract

The endothelial-to-mesenchymal transition (EndoMT) is involved in the complex pathogenesis of renal fibrosis. The soluble proteoglycan endothelial cell-specific molecule 1 (ESM1) is significantly upregulated in many tumor cells and cirrhosis-related disease. The role of ESM1 in renal fibrosis is unknown. This study investigates [...] Read more.

The endothelial-to-mesenchymal transition (EndoMT) is involved in the complex pathogenesis of renal fibrosis. The soluble proteoglycan endothelial cell-specific molecule 1 (ESM1) is significantly upregulated in many tumor cells and cirrhosis-related disease. The role of ESM1 in renal fibrosis is unknown. This study investigates the role of ESM1 in renal fibrosis, using an in vivo unilateral ureteral obstruction (UUO) mouse model of renal fibrosis and in vitro mouse kidney MES 13 cells overexpressing ESM1. We observed that ESM1 overexpression significantly increased the motility and migration of MES 13 cells, independent of cell viability. In ESM1-overexpressing MES 13 cells, we also observed elevated expression of mesenchymal markers (N-cadherin, vimentin, matrix metallopeptidase 9 (MMP9)) and the fibrosis marker α-smooth muscle actin (α-SMA) and decreased expression of the endothelial marker vascular endothelial cadherin (VE-cadherin) and CD31. In a mouse model of fibrosis induced by unilateral ureter obstruction, we observed time-dependent increases in ESM1, α-SMA, and vimentin expression and renal interstitial collagen fibers in kidney tissue samples. These results suggest that ESM1 may serve as an EndoMT marker of renal fibrosis progression. Full article

(This article belongs to the Special Issue Chronic Kidney Disease (CKD) Studies on Humans and Animals)

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25 pages, 1381 KiB

Open AccessReview

α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia

by Adam C. Kennedy, Alessia Belgi, Benjamin W. Husselbee, David Spanswick, Raymond S. Norton and Andrea J. Robinson

Toxins 2020, 12(8), 505; https://doi.org/10.3390/toxins12080505 - 06 Aug 2020

Cited by 19 | Viewed by 4515

Abstract

Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides has provided potent and selective analogues for two of its known biological targets—nicotinic acetylcholine and γ-aminobutyric acid (GABA) G protein-coupled (GABA_B) receptors. Both of these molecular [...] Read more.

Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides has provided potent and selective analogues for two of its known biological targets—nicotinic acetylcholine and γ-aminobutyric acid (GABA) G protein-coupled (GABA_B) receptors. Both of these molecular targets are implicated in pain pathways. Despite their small size, an incomplete understanding of the structure-activity relationship of α-conotoxins at each of these targets has hampered the development of therapeutic leads. This review scrutinises the N-terminal domain of the α-conotoxin family of peptides, a region defined by an invariant disulfide bridge, a turn-inducing proline residue and multiple polar sidechain residues, and focusses on structural features that provide analgesia through inhibition of high-voltage-activated Ca²⁺ channels. Elucidating the bioactive conformation of this region of these peptides may hold the key to discovering potent drugs for the unmet management of debilitating chronic pain associated with a wide range of medical conditions. Full article

(This article belongs to the Special Issue Conotoxins: Characterization, Pharmacology, and Therapeutics)

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19 pages, 1102 KiB

Open AccessEditor’s ChoiceArticle

Investigation of the Efficacy of a Postbiotic Yeast Cell Wall-Based Blend on Newly-Weaned Pigs under a Dietary Challenge of Multiple Mycotoxins with Emphasis on Deoxynivalenol

by Debora Muratori Holanda, Alexandros Yiannikouris and Sung Woo Kim

Toxins 2020, 12(8), 504; https://doi.org/10.3390/toxins12080504 - 06 Aug 2020

Cited by 45 | Viewed by 4186

Abstract

Pigs are highly susceptible to mycotoxins. This study investigated the effects of a postbiotic yeast cell wall-based blend (PYCW; Nicholasville, KY, USA) on growth and health of newly-weaned pigs under dietary challenge of multiple mycotoxins. Forty-eight newly-weaned pigs (21 d old) were individually [...] Read more.

Pigs are highly susceptible to mycotoxins. This study investigated the effects of a postbiotic yeast cell wall-based blend (PYCW; Nicholasville, KY, USA) on growth and health of newly-weaned pigs under dietary challenge of multiple mycotoxins. Forty-eight newly-weaned pigs (21 d old) were individually allotted to four dietary treatments, based on a three phase-feeding, in a randomized complete block design (sex; initial BW) with two factors for 36 d. Two factors were dietary mycotoxins (deoxynivalenol: 2000 μg/kg supplemented in three phases; and aflatoxin: 200 μg/kg supplemented only in phase 3) and PYCW (0.2%). Growth performance (weekly), blood serum (d 34), and jejunal mucosa immune and oxidative stress markers (d 36) data were analyzed using MIXED procedure of SAS. Mycotoxins reduced (p < 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the entire period whereas PYCW did not affect growth performance. Mycotoxins reduced (p < 0.05) serum protein, albumin, creatinine, and alanine aminotransferase whereas PYCW decreased (p < 0.05) serum creatine phosphokinase. Neither mycotoxins nor PYCW affected pro-inflammatory cytokines and oxidative damage markers in the jejunal mucosa. No interaction was observed indicating that PYCW improved hepatic enzymes regardless of mycotoxin challenge. In conclusion, deoxynivalenol (2000 μg/kg, for 7 to 25 kg body weight) and aflatoxin B1 (200 μg/kg, for 16 to 25 kg body weight) impaired growth performance and nutrient digestibility of newly-weaned pigs, whereas PYCW could partially improve health of pigs regardless of mycotoxin challenge. Full article

(This article belongs to the Special Issue Impact of Naturally Contaminated Mycotoxins in Feedstuffs and Feeds on Animal Growth and Health)

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15 pages, 2378 KiB

Open AccessArticle

Cyanobacterial Abundance and Microcystin Profiles in Two Southern British Lakes: The Importance of Abiotic and Biotic Interactions

by David M. Hartnell, Ian J. Chapman, Nick G. H. Taylor, Genoveva F. Esteban, Andrew D. Turner and Daniel J. Franklin

Toxins 2020, 12(8), 503; https://doi.org/10.3390/toxins12080503 - 05 Aug 2020

Cited by 9 | Viewed by 3198

Abstract

Freshwater cyanobacteria blooms represent a risk to ecological and human health through induction of anoxia and release of potent toxins; both conditions require water management to mitigate risks. Many cyanobacteria taxa may produce microcystins, a group of toxic cyclic heptapeptides. Understanding the relationships [...] Read more.

Freshwater cyanobacteria blooms represent a risk to ecological and human health through induction of anoxia and release of potent toxins; both conditions require water management to mitigate risks. Many cyanobacteria taxa may produce microcystins, a group of toxic cyclic heptapeptides. Understanding the relationships between the abiotic drivers of microcystins and their occurrence would assist in the implementation of targeted, cost-effective solutions to maintain safe drinking and recreational waters. Cyanobacteria and microcystins were measured by flow cytometry and liquid chromatography coupled to tandem mass spectrometry in two interconnected reservoirs varying in age and management regimes, in southern Britain over a 12-month period. Microcystins were detected in both reservoirs, with significantly higher concentrations in the southern lake (maximum concentration >7 µg L⁻¹). Elevated microcystin concentrations were not positively correlated with numbers of cyanobacterial cells, but multiple linear regression analysis suggested temperature and dissolved oxygen explained a significant amount of the variability in microcystin across both reservoirs. The presence of a managed fishery in one lake was associated with decreased microcystin levels, suggestive of top down control on cyanobacterial populations. This study supports the need to develop inclusive, multifactor holistic water management strategies to control cyanobacterial risks in freshwater bodies. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

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14 pages, 2076 KiB

Open AccessArticle

Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase

by Shoma Tanaka, Hiroshi Watanabe, Takehiro Nakano, Tadashi Imafuku, Hiromasa Kato, Kai Tokumaru, Nanaka Arimura, Yuki Enoki, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa and Toru Maruyama

Toxins 2020, 12(8), 502; https://doi.org/10.3390/toxins12080502 - 05 Aug 2020

Cited by 19 | Viewed by 3702

Abstract

Adipose tissue inflammation appears to be a risk factor for the progression of chronic kidney disease (CKD), but the effect of CKD on adipose tissue inflammation is poorly understood. The purpose of this study was to clarify the involvement of uremic toxins (indoxyl [...] Read more.

Adipose tissue inflammation appears to be a risk factor for the progression of chronic kidney disease (CKD), but the effect of CKD on adipose tissue inflammation is poorly understood. The purpose of this study was to clarify the involvement of uremic toxins (indoxyl sulfate (IS), 3-indoleacetic acid, p-cresyl sulfate and kynurenic acid) on CKD-induced adipose tissue inflammation. IS induces monocyte chemoattractant protein-1 (MCP-1) expression and reactive oxygen species (ROS) production in the differentiated 3T3L-1 adipocyte. An organic anion transporter (OAT) inhibitor, an NADPH oxidase inhibitor or an antioxidant suppresses the IS-induced MCP-1 expression and ROS production, suggesting the OAT/NADPH oxidase/ROS pathway is involved in the action of IS. Co-culturing 3T3L-1 adipocytes and mouse macrophage cells showed incubating adipocytes with IS increased macrophage infiltration. An IS-overload in healthy mice increased IS levels, oxidative stress and MCP-1 expression in epididymal adipose tissue compared to unloaded mice. Using 5/6-nephrectomized mice, the administration of AST-120 suppressed oxidative stress and the expression of MCP-1, F4/80 and TNF-α in epididymal adipose tissue. These collective data suggest IS could be a therapeutic target for the CKD-related inflammatory response in adipose tissue, and that AST-120 could be useful for the treatment of IS-induced adipose tissue inflammation. Full article

(This article belongs to the Special Issue Role of Uremic Toxins in Vascular Calcification, Vascular Disease and Bone Dysfunction)

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18 pages, 5554 KiB

Open AccessArticle

Proteotranscriptomic Insights into the Venom Composition of the Wolf Spider Lycosa tarantula

by Dominique Koua, Rosanna Mary, Anicet Ebou, Celia Barrachina, Khadija El Koulali, Guillaume Cazals, Pierre Charnet and Sebastien Dutertre

Toxins 2020, 12(8), 501; https://doi.org/10.3390/toxins12080501 - 05 Aug 2020

Cited by 8 | Viewed by 9373

Abstract

Spider venoms represent an original source of novel compounds with therapeutic and agrochemical potential. Whereas most of the research efforts have focused on large mygalomorph spiders, araneomorph spiders are equally promising but require more sensitive and sophisticated approaches given their limited size and [...] Read more.

Spider venoms represent an original source of novel compounds with therapeutic and agrochemical potential. Whereas most of the research efforts have focused on large mygalomorph spiders, araneomorph spiders are equally promising but require more sensitive and sophisticated approaches given their limited size and reduced venom yield. Belonging to the latter group, the genus Lycosa (“wolf spiders”) contains many species widely distributed throughout the world. These spiders are ambush predators that do not build webs but instead rely strongly on their venom for prey capture. Lycosa tarantula is one of the largest species of wolf spider, but its venom composition is unknown. Using a combination of RNA sequencing of the venom glands and venom proteomics, we provide the first overview of the peptides and proteins produced by this iconic Mediterranean spider. Beside the typical small disulfide rich neurotoxins, several families of proteins were also identified, including cysteine-rich secretory proteins (CRISP) and Hyaluronidases. Proteomic analysis of the electrically stimulated venom validated 30 of these transcriptomic sequences, including nine putative neurotoxins and eight venom proteins. Interestingly, LC-MS venom profiles of manual versus electric stimulation, as well as female versus male, showed some marked differences in mass distribution. Finally, we also present some preliminary data on the biological activity of L. tarantula crude venom. Full article

(This article belongs to the Special Issue Venom Proteomics and Transcriptomics)

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17 pages, 4932 KiB

Open AccessCommunication

Evaluation of Antifungal Activity of Naja pallida and Naja mossambica Venoms against Three Candida Species

by Ewelina Kuna, Aleksandra Bocian, Konrad K. Hus, Vladimir Petrilla, Monika Petrillova, Jaroslav Legath, Anna Lewinska and Maciej Wnuk

Toxins 2020, 12(8), 500; https://doi.org/10.3390/toxins12080500 - 04 Aug 2020

Cited by 6 | Viewed by 3574

Abstract

In contrast to comprehensively investigated antibacterial activity of snake venoms, namely crude venoms and their selected components, little is known about antifungal properties of elapid snake venoms. In the present study, the proteome of two venoms of red spitting cobra Naja pallida (NPV) [...] Read more.

In contrast to comprehensively investigated antibacterial activity of snake venoms, namely crude venoms and their selected components, little is known about antifungal properties of elapid snake venoms. In the present study, the proteome of two venoms of red spitting cobra Naja pallida (NPV) and Mozambique spitting cobra Naja mossambica (NMV) was characterized using LC-MS/MS approach, and the antifungal activity of crude venoms against three Candida species was established. A complex response to venom treatment was revealed. NPV and NMV, when used at relatively high concentrations, decreased cell viability of C. albicans and C. tropicalis, affected cell cycle of C. albicans, inhibited C. tropicalis-based biofilm formation and promoted oxidative stress in C. albicans, C. glabrata and C. tropicalis cells. NPV and NMV also modulated ammonia pulses during colony development and aging in three Candida species. All these observations provide evidence that NPV and NMV may diminish selected pathogenic features of Candida species. However, NPV and NMV also promoted the secretion of extracellular phospholipases that may facilitate Candida pathogenicity and limit their usefulness as anti-candidal agents. In conclusion, antifungal activity of snake venoms should be studied with great caution and a plethora of pathogenic biomarkers should be considered in the future experiments. Full article

(This article belongs to the Special Issue Drug Development Using Natural Toxins)

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15 pages, 2667 KiB

Open AccessPerspective

Clinical Implications of Difference in Antigenicity of Different Botulinum Neurotoxin Type A Preparations: Clinical Take-Home Messages from Our Research Pool and Literature

by Sara Samadzadeh, Beyza Ürer, Raphaela Brauns, Dietmar Rosenthal, John-Ih Lee, Philipp Albrecht and Harald Hefter

Toxins 2020, 12(8), 499; https://doi.org/10.3390/toxins12080499 - 04 Aug 2020

Cited by 19 | Viewed by 3377

Abstract

The three different botulinum toxin type A (BoNT/A) preparations being licensed in Europe and the U.S. differ in protein content, which seems to be a major factor influencing the antigenicity of BoNT/A. In the present study, several arguments out of our research pool [...] Read more.

The three different botulinum toxin type A (BoNT/A) preparations being licensed in Europe and the U.S. differ in protein content, which seems to be a major factor influencing the antigenicity of BoNT/A. In the present study, several arguments out of our research pool were collected to demonstrate that the clinical response and antigenicity were different for the three BoNT/A preparations: some results of (1) a cross-sectional study on clinical outcome and antibody formation of 212 patients with cervical dystonia (CD) being treated between 2 and 22 years; (2) another cross-sectional study on the clinical aspects and neutralizing antibody (NAB) induction of 63 patients having developed partial secondary treatment under abobotulinum (aboBoNT/A) onabotulinumtoxin (onaBoNT/A) who were switched to incobotulinumtoxin (incoBoNT/A) in comparison to 32 patients being exclusively treated with incoBoNT/A. These results imply that (1) the presence of NAB cannot be concluded from the course of treatment, that (2) an increase in the dose and variability of outcome with treatment duration indicates the ongoing induction of NABs over time, that (3) the higher protein load of BoNT/A goes along with a higher incidence and prevalence of NAB induction and that (4) the best response to a BoNT/A is also dependent on the protein load of the preparation. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin Injection)

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11 pages, 829 KiB

Open AccessArticle

Determination of Aflatoxin M1 in Raw Milk from Different Provinces of Ecuador

by Byron Puga-Torres, David Salazar, Mayra Cachiguango, Gabriela Cisneros and Carlos Gómez-Bravo

Toxins 2020, 12(8), 498; https://doi.org/10.3390/toxins12080498 - 03 Aug 2020

Cited by 15 | Viewed by 4687

Abstract

Aflatoxin M1 (AFM1) is a mycotoxin from Aspergillus flavus and A. parasiticus, classified as carcinogenic and hepatotoxic. The objective of the present investigation was to determine its presence in raw milk from north-central Ecuador, constituted by the provinces of Pichincha, Manabí, and [...] Read more.

Aflatoxin M1 (AFM1) is a mycotoxin from Aspergillus flavus and A. parasiticus, classified as carcinogenic and hepatotoxic. The objective of the present investigation was to determine its presence in raw milk from north-central Ecuador, constituted by the provinces of Pichincha, Manabí, and Santo Domingo de los Tsáchilas. These areas represent approximately 30% of Ecuadorian milk production. By the end of the investigation, a total of 209 raw milk samples were collected, obtained both during the dry (June and August) and rainy seasons (April and November) of 2019. AFM1 concentrations were measured with lateral flow immunochromatographic assays, and 100% of the samples were positive for this mycotoxin, presenting a mean value of 0.0774 μg/kg with a range of 0.023 to 0.751 μg/kg. These AFM1 levels exceeded the European Union regulatory limit of 0.05 μg/kg in 59.3% (124/209) of samples, while only 1.9% (4/209) exceeded the Ecuadorian legal limit of 0.5 μg/kg. By using non-parametric tests, significant differences were determined (p ≤ 0.05) between the provinces for months of study, climatic season (being higher in the dry season), and climatic region (greater in the coast region). On the other hand, there were no significant differences (p ≥ 0.05) between the types of producers or between production systems. Therefore, AFM1 contamination in raw milk does not present a serious public health problem in Ecuador, but a monitoring and surveillance program for this mycotoxin in milk should be developed to prevent consumer health problems. Full article

(This article belongs to the Special Issue Occurrence, Toxicity and Mitigation of Aflatoxins)

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