Toxins

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Open AccessArticle

Determination of Mycotoxin Production of Fusarium Species in Genetically Modified Maize Varieties by Quantitative Flow Immunocytometry

by Hajnalka Bánáti, Béla Darvas, Szilvia Fehér-Tóth, Árpád Czéh and András Székács

Toxins 2017, 9(2), 70; https://doi.org/10.3390/toxins9020070 - 22 Feb 2017

Cited by 14 | Viewed by 6069

Abstract

Levels of mycotoxins produced by Fusarium species in genetically modified (GM) and near-isogenic maize, were determined using multi-analyte, microbead-based flow immunocytometry with fluorescence detection, for the parallel quantitative determination of fumonisin B1, deoxynivalenol, zearalenone, T-2, ochratoxin A, and aflatoxin B1. Maize varieties included [...] Read more.

Levels of mycotoxins produced by Fusarium species in genetically modified (GM) and near-isogenic maize, were determined using multi-analyte, microbead-based flow immunocytometry with fluorescence detection, for the parallel quantitative determination of fumonisin B1, deoxynivalenol, zearalenone, T-2, ochratoxin A, and aflatoxin B1. Maize varieties included the genetic events MON 810 and DAS-59122-7, and their isogenic counterparts. Cobs were artificially infested by F. verticillioides and F. proliferatum conidia, and contained F. graminearum and F. sporotrichoides natural infestation. The production of fumonisin B1 and deoxynivalenol was substantially affected in GM maize lines: F. verticillioides, with the addition of F. graminearum and F. sporotrichoides, produced significantly lower levels of fumonisin B1 (~300 mg·kg⁻¹) in DAS-59122-7 than in its isogenic line (~580 mg·kg⁻¹), while F. proliferatum, in addition to F. graminearum and F. sporotrichoides, produced significantly higher levels of deoxynivalenol (~18 mg·kg⁻¹) in MON 810 than in its isogenic line (~5 mg·kg⁻¹). Fusarium verticillioides, with F. graminearum and F. sporotrichoides, produced lower amounts of deoxynivalenol and zearalenone than F. proliferatum, with F. graminearum and F. sporotrichoides. T-2 toxin production remained unchanged when considering the maize variety. The results demonstrate the utility of the Fungi-Plex™ quantitative flow immunocytometry method, applied for the high throughput parallel determination of the target mycotoxins. Full article

(This article belongs to the Section Mycotoxins)

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Open AccessArticle

Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

by Andrew I. Selwood, Craig Waugh, David T. Harwood, Lesley L. Rhodes, John Reeve, Jim Sim and Rex Munday

Toxins 2017, 9(2), 73; https://doi.org/10.3390/toxins9020073 - 21 Feb 2017

Cited by 32 | Viewed by 6902

Abstract

Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay [...] Read more.

Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health. Full article

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

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Open AccessArticle

Static Hot Air and Infrared Rays Roasting are Efficient Methods for Aflatoxin Decontamination on Hazelnuts

by Ilenia Siciliano, Barbara Dal Bello, Giuseppe Zeppa, Davide Spadaro and Maria Lodovica Gullino

Toxins 2017, 9(2), 72; https://doi.org/10.3390/toxins9020072 - 21 Feb 2017

Cited by 22 | Viewed by 5055

Abstract

Aflatoxins are a group of secondary metabolites produced by members of Aspergillus Section Flavi that are dangerous to humans and animals. Nuts can be potentially contaminated with aflatoxins, often over the legal threshold. Food processes, including roasting, may have different effects on mycotoxins, [...] Read more.

Aflatoxins are a group of secondary metabolites produced by members of Aspergillus Section Flavi that are dangerous to humans and animals. Nuts can be potentially contaminated with aflatoxins, often over the legal threshold. Food processes, including roasting, may have different effects on mycotoxins, and high temperatures have proven to be very effective in the reduction of mycotoxins. In this work, two different roasting methods—traditional static hot air roasting and infra-red rays roasting—were applied and compared for the detoxification of hazelnuts from Italy and Turkey. At the temperature of 140 °C for 40 min of exposure, detoxification was effective for both roasting techniques. Residual aflatoxins after infra-red rays treatments were lower compared to static hot air roasting. On Italian hazelnuts, residual aflatoxins were lower than 5%, while for Turkish hazelnuts they were lower than 15% after 40 min of exposure to an infra-red rays roaster. After roasting, the perisperm was detached from the nuts and analyzed for aflatoxin contents. Residual aflatoxins in the perisperm ranged from 80% up to 100%. After roasting, the lipid profile and the nutritional quality of hazelnuts were not affected. Fatty acid methyl esters analyses showed a similar composition for Italian and Turkish hazelnuts. Full article

(This article belongs to the Special Issue Promising Detoxification Strategies to Mitigate Mycotoxins in Food and Feed)

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Open AccessReview

Fungal Ribotoxins: A Review of Potential Biotechnological Applications

by Miriam Olombrada, Rodrigo Lázaro-Gorines, Juan C. López-Rodríguez, Álvaro Martínez-del-Pozo, Mercedes Oñaderra, Moisés Maestro-López, Javier Lacadena, José G. Gavilanes and Lucía García-Ortega

Toxins 2017, 9(2), 71; https://doi.org/10.3390/toxins9020071 - 21 Feb 2017

Cited by 63 | Viewed by 10261

Abstract

Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these toxins, ribotoxins stand out as promising candidates for their use in biotechnological applications. They [...] Read more.

Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these toxins, ribotoxins stand out as promising candidates for their use in biotechnological applications. They constitute a group of highly specific extracellular ribonucleases that target a universally conserved sequence of RNA in the ribosome, the sarcin-ricin loop. The detailed molecular study of this family of toxic proteins over the past decades has highlighted their potential in applied research. Remarkable examples would be the recent studies in the field of cancer research with promising results involving ribotoxin-based immunotoxins. On the other hand, some ribotoxin-producer fungi have already been studied in the control of insect pests. The recent role of ribotoxins as insecticides could allow their employment in formulas and even as baculovirus-based biopesticides. Moreover, considering the important role of their target in the ribosome, they can be used as tools to study how ribosome biogenesis is regulated and, eventually, may contribute to a better understanding of some ribosomopathies. Full article

(This article belongs to the Section Mycotoxins)

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Open AccessArticle

Comparative Transcriptome Analysis of Penicillium citrinum Cultured with Different Carbon Sources Identifies Genes Involved in Citrinin Biosynthesis

by Taotao Li, Guoxiang Jiang, Hongxia Qu, Yong Wang, Yehui Xiong, Qijie Jian, Yu Wu, Xuewu Duan, Xiangrong Zhu, Wenzhong Hu, Jiasheng Wang, Liang Gong and Yueming Jiang

Toxins 2017, 9(2), 69; https://doi.org/10.3390/toxins9020069 - 21 Feb 2017

Cited by 28 | Viewed by 6352

Abstract

Citrinin is a toxic secondary metabolite of Penicillium citrinum and its contamination in many food items has been widely reported. However, research on the citrinin biosynthesis pathway and its regulation mechanism in P. citrinum is rarely reported. In this study, we investigated the [...] Read more.

Citrinin is a toxic secondary metabolite of Penicillium citrinum and its contamination in many food items has been widely reported. However, research on the citrinin biosynthesis pathway and its regulation mechanism in P. citrinum is rarely reported. In this study, we investigated the effect of different carbon sources on citrinin production by P. citrinum and used transcriptome analysis to study the underlying molecular mechanism. Our results indicated that glucose, used as the sole carbon source, could significantly promote citrinin production by P. citrinum in Czapek’s broth medium compared with sucrose. A total of 19,967 unigenes were annotated by BLAST in Nr, Nt, Swiss-Prot and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Transcriptome comparison between P. citrinum cultured with sucrose and glucose revealed 1085 differentially expressed unigenes. Among them, 610 were upregulated while 475 were downregulated under glucose as compared to sucrose. KEGG pathway and Gene ontology (GO) analysis indicated that many metabolic processes (e.g., carbohydrate, secondary metabolism, fatty acid and amino acid metabolism) were affected, and potentially interesting genes that encoded putative components of signal transduction, stress response and transcription factor were identified. These genes obviously had important impacts on their regulation in citrinin biosynthesis, which provides a better understanding of the molecular mechanism of citrinin biosynthesis by P. citrinum. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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Open AccessArticle

Toxin Release of Cyanobacterium Microcystis aeruginosa after Exposure to Typical Tetracycline Antibiotic Contaminants

by Jing Ye, Yuping Du, Lumei Wang, Jingru Qian, Jiejing Chen, Qingwen Wu and Xiaojun Hu

Toxins 2017, 9(2), 53; https://doi.org/10.3390/toxins9020053 - 21 Feb 2017

Cited by 48 | Viewed by 5640

Abstract

The global usage of veterinary antibiotics is significant. Antibiotics can be released into aquatic environments and elicit toxic effects on non-target organisms. In this study, the growth characteristics and toxin release of the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were examined to [...] Read more.

The global usage of veterinary antibiotics is significant. Antibiotics can be released into aquatic environments and elicit toxic effects on non-target organisms. In this study, the growth characteristics and toxin release of the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were examined to investigate the physiological effects of tetracycline antibiotics on aquatic life. Results showed that the degree of toxicities of the following target antibiotics was TC (tetracycline hydrochloride) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline hydrochloride) in terms of growth parameters, EC₁₀ (0.63, 1.86, and 3.02 mg/L, respectively), and EC₂₀ (1.58, 4.09, and 4.86 mg/L, respectively) values. These antibiotics inhibited the production of microcystin-LR (MC-LR) to varying degrees. CTC interfered M. aeruginosa cells and decreased their ability to release MC-LR, but this antibiotic stimulated the ability of these cells to synthesize MC-LR at 2 and 5 mg/L. OTC elicited a relatively weaker toxicity than CTC did and reduced MC-LR release. TC was the most toxic among the three antibiotics, and this antibiotic simultaneously reduced intracellular and extracellular MC-LR equivalents. Our results helped elucidate the effects of tetracycline antibiotics on M. aeruginosa, which is essential for environmental evaluation and protection. Our results are also helpful for guiding the application of veterinary antibiotics in agricultural settings. Full article

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

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Open AccessArticle

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

by Kyung-Hwa Jung, Hyunjung Baek, Manho Kang, Namsik Kim, Seung Young Lee and Hyunsu Bae

Toxins 2017, 9(2), 68; https://doi.org/10.3390/toxins9020068 - 18 Feb 2017

Cited by 22 | Viewed by 7493

Abstract

Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic [...] Read more.

Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD. Full article

(This article belongs to the Special Issue Animal Venoms and Pain)

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Open AccessArticle

Human scFvs That Counteract Bioactivities of Staphylococcus aureus TSST-1

by Thunchanok Rukkawattanakul, Nitat Sookrung, Watee Seesuay, Nattawat Onlamoon, Pornphan Diraphat, Wanpen Chaicumpa and Nitaya Indrawattana

Toxins 2017, 9(2), 50; https://doi.org/10.3390/toxins9020050 - 17 Feb 2017

Cited by 15 | Viewed by 6632

Abstract

Some Staphylococcus aureus isolates produced toxic shock syndrome toxin-1 (TSST-1) which is a pyrogenic toxin superantigen (PTSAg). The toxin activates a large fraction of peripheral blood T lymphocytes causing the cells to proliferate and release massive amounts of pro-inflammatory cytokines leading to a [...] Read more.

Some Staphylococcus aureus isolates produced toxic shock syndrome toxin-1 (TSST-1) which is a pyrogenic toxin superantigen (PTSAg). The toxin activates a large fraction of peripheral blood T lymphocytes causing the cells to proliferate and release massive amounts of pro-inflammatory cytokines leading to a life-threatening multisystem disorder: toxic shock syndrome (TSS). PTSAg-mediated-T cell stimulation circumvents the conventional antigenic peptide presentation to T cell receptor (TCR) by the antigen-presenting cell (APC). Instead, intact PTSAg binds directly to MHC-II molecule outside peptide binding cleft and simultaneously cross-links TCR-Vβ region. Currently, there is neither specific TSS treatment nor drug that directly inactivates TSST-1. In this study, human single chain antibodies (HuscFvs) that bound to and neutralized bioactivities of the TSST-1 were generated using phage display technology. Three E. coli clones transfected with TSST-1-bound phages fished-out from the human scFv library using recombinant TSST-1 as bait expressed TSST-1-bound-HuscFvs that inhibited the TSST-1-mediated T cell activation and pro-inflammatory cytokine gene expressions and productions.Computerized simulation, verified by mutations of the residues of HuscFv complementarity determining regions (CDRs),predicted to involve in target binding indicated that the HuscFvs formed interface contact with the toxin residues important for immunopathogenesis. The HuscFvs have high potential for future therapeutic application. Full article

(This article belongs to the Collection Staphylococcus aureus Toxins)

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Open AccessArticle

The Cardiovascular and Neurotoxic Effects of the Venoms of Six Bony and Cartilaginous Fish Species

by Han Han, Kate Baumann, Nicholas R. Casewell, Syed A. Ali, James Dobson, Ivan Koludarov, Jordan Debono, Scott C. Cutmore, Niwanthi W. Rajapakse, Timothy N. W. Jackson, Rob Jones, Wayne C. Hodgson, Bryan G. Fry and Sanjaya Kuruppu

Toxins 2017, 9(2), 67; https://doi.org/10.3390/toxins9020067 - 16 Feb 2017

Cited by 4 | Viewed by 8669

Abstract

Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii [...] Read more.

Fish venoms are often poorly studied, in part due to the difficulty in obtaining, extracting, and storing them. In this study, we characterize the cardiovascular and neurotoxic effects of the venoms from the following six species of fish: the cartilaginous stingrays Neotrygon kuhlii and Himantura toshi, and the bony fish Platycephalus fucus, Girella tricuspidata, Mugil cephalus, and Dentex tumifrons. All venoms (10–100 μg/kg, i.v.), except G. tricuspidata and P. fuscus, induced a biphasic response on mean arterial pressure (MAP) in the anesthetised rat. P. fucus venom exhibited a hypotensive response, while venom from G. tricuspidata displayed a single depressor response. All venoms induced cardiovascular collapse at 200 μg/kg, i.v. The in vitro neurotoxic effects of venom were examined using the chick biventer cervicis nerve‐muscle (CBCNM) preparation. N. kuhlii, H. toshi, and P. fucus venoms caused concentration‐dependent inhibition of indirect twitches in the CBCNM preparation. These three venoms also inhibited responses to exogenous acetylcholine (ACh) and carbachol (CCh), but not potassium chloride (KCl), indicating a post‐synaptic mode of action. Venom from G. tricuspidata, M. cephalus, and D. tumifrons had no significant effect on indirect twitches or agonist responses in the CBCNM. Our results demonstrate that envenoming by these species of fish may result in moderate cardiovascular and/or neurotoxic effects. Future studies aimed at identifying the molecules responsible for these effects could uncover potentially novel lead compounds for future pharmaceuticals, in addition to generating new knowledge about the evolutionary relationships between venomous animals. Full article

(This article belongs to the Section Animal Venoms)

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Open AccessReply

Reply to Comment on “Screening and Identification of Novel Ochratoxin A-Producing Fungi from Grapes”. Toxins 2016, 8, 333”–in Reporting Ochratoxin A Production from Strains of Aspergillus, Penicillium and Talaromyces

by Xiaoyun Zhang, Yulin Li, Haiying Wang, Xiangyu Gu, Xiangfeng Zheng, Yun Wang, Junwei Diao, Yaping Peng and Hongyin Zhang

Toxins 2017, 9(2), 66; https://doi.org/10.3390/toxins9020066 - 14 Feb 2017

Cited by 3 | Viewed by 4319

Abstract

We sincerely thank you and Dr. Giancarlo Perrone, Antonio F. Logrieco and Jens C. Frisvda for the suggestions and concerns raised with regard to our paper entitled “Screening and Identification of Novel ochratoxin A-Producing Fungi from Grapes” which was published in Toxins.[...] Full article

(This article belongs to the Collection Ochratoxins-Collection)

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Open AccessComment

Comments on “Screening and Identification of Novel Ochratoxin A-Producing Fungi from Grapes. Toxins 2016, 8, 333”—In Reporting Ochratoxin A Production from Strains of Aspergillus, Penicillium and Talaromyces

by Giancarlo Perrone, Antonio F. Logrieco and Jens C. Frisvad

Toxins 2017, 9(2), 65; https://doi.org/10.3390/toxins9020065 - 14 Feb 2017

Cited by 11 | Viewed by 4533

Abstract

Recently a species in the genus Talaromyces, a uniseriate species of Aspergillus section Nigri and an isolate each of two widespread species, Penicillium rubens and P. commune, were reported to produce ochratoxin A. This claim was based on insufficient biological and [...] Read more.

Recently a species in the genus Talaromyces, a uniseriate species of Aspergillus section Nigri and an isolate each of two widespread species, Penicillium rubens and P. commune, were reported to produce ochratoxin A. This claim was based on insufficient biological and chemical data. We propose a list of criteria that need to be met before an unexpected mycotoxin producer is reported. There have only been convincing data on ochratoxin A production for Penicillium verrucosum, P. nordicum, P. thymicola, all from Penicillium series Verrucosa, and from species in three sections of Aspergillus: section Circumdati, section Nigri and section Flavi. Full article

(This article belongs to the Collection Ochratoxins-Collection)

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Open AccessArticle

Microbial Detoxification of Deoxynivalenol (DON), Assessed via a Lemna minor L. Bioassay, through Biotransformation to 3-epi-DON and 3-epi-DOM-1

by Ilse Vanhoutte, Laura De Mets, Marthe De Boevre, Valdet Uka, José Diana Di Mavungu, Sarah De Saeger, Leen De Gelder and Kris Audenaert

Toxins 2017, 9(2), 63; https://doi.org/10.3390/toxins9020063 - 13 Feb 2017

Cited by 31 | Viewed by 6826

Abstract

Mycotoxins are toxic metabolites produced by fungi. To mitigate mycotoxins in food or feed, biotransformation is an emerging technology in which microorganisms degrade toxins into non-toxic metabolites. To monitor deoxynivalenol (DON) biotransformation, analytical tools such as ELISA and liquid chromatography coupled to tandem [...] Read more.

Mycotoxins are toxic metabolites produced by fungi. To mitigate mycotoxins in food or feed, biotransformation is an emerging technology in which microorganisms degrade toxins into non-toxic metabolites. To monitor deoxynivalenol (DON) biotransformation, analytical tools such as ELISA and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) are typically used. However, these techniques do not give a decisive answer about the remaining toxicity of possible biotransformation products. Hence, a bioassay using Lemna minor L. was developed. A dose–response analysis revealed significant inhibition in the growth of L. minor exposed to DON concentrations of 0.25 mg/L and higher. Concentrations above 1 mg/L were lethal for the plant. This bioassay is far more sensitive than previously described systems. The bioassay was implemented to screen microbial enrichment cultures, originating from rumen fluid, soil, digestate and activated sludge, on their biotransformation and detoxification capability of DON. The enrichment cultures originating from soil and activated sludge were capable of detoxifying and degrading 5 and 50 mg/L DON. In addition, the metabolites 3-epi-DON and the epimer of de-epoxy-DON (3-epi-DOM-1) were found as biotransformation products of both consortia. Our work provides a new valuable tool to screen microbial cultures for their detoxification capacity. Full article

(This article belongs to the Special Issue Selected Papers from the 5th International Symposium on Mycotoxins and Toxigenic Moulds: Challenges and Perspectives)

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Open AccessArticle

Eutrophication and Warming Boost Cyanobacterial Biomass and Microcystins

by Miquel Lürling, Frank Van Oosterhout and Elisabeth Faassen

Toxins 2017, 9(2), 64; https://doi.org/10.3390/toxins9020064 - 11 Feb 2017

Cited by 103 | Viewed by 9815

Abstract

Eutrophication and warming are key drivers of cyanobacterial blooms, but their combined effects on microcystin (MC) concentrations are less studied. We tested the hypothesis that warming promotes cyanobacterial abundance in a natural plankton community and that eutrophication enhances cyanobacterial biomass and MC concentrations. [...] Read more.

Eutrophication and warming are key drivers of cyanobacterial blooms, but their combined effects on microcystin (MC) concentrations are less studied. We tested the hypothesis that warming promotes cyanobacterial abundance in a natural plankton community and that eutrophication enhances cyanobacterial biomass and MC concentrations. We incubated natural seston from a eutrophic pond under normal, high, and extreme temperatures (i.e., 20, 25, and 30 °C) with and without additional nutrients added (eutrophication) mimicking a pulse as could be expected from projected summer storms under climate change. Eutrophication increased algal- and cyanobacterial biomass by 26 and 8 times, respectively, and led to 24 times higher MC concentrations. This effect was augmented with higher temperatures leading to 45 times higher MC concentrations at 25 °C, with 11 times more cyanobacterial chlorophyll-a and 25 times more eukaryote algal chlorophyll-a. At 30 °C, MC concentrations were 42 times higher, with cyanobacterial chlorophyll-a being 17 times and eukaryote algal chlorophyll-a being 24 times higher. In contrast, warming alone did not yield more cyanobacteria or MCs, because the in situ community had already depleted the available nutrient pool. MC per potential MC producing cell declined at higher temperatures under nutrient enrichments, which was confirmed by a controlled experiment with two laboratory strains of Microcystis aeruginosa. Nevertheless, MC concentrations were much higher at the increased temperature and nutrient treatment than under warming alone due to strongly promoted biomass, lifting N-imitation and promotion of potential MC producers like Microcystis. This study exemplifies the vulnerability of eutrophic urban waters to predicted future summer climate change effects that might aggravate cyanobacterial nuisance. Full article

(This article belongs to the Collection Freshwater HABs and Health in a Changing World)

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Open AccessArticle

Variable Cyanobacterial Toxin and Metabolite Profiles across Six Eutrophic Lakes of Differing Physiochemical Characteristics

by Lucas J. Beversdorf, Chelsea A. Weirich, Sarah L. Bartlett and Todd. R. Miller

Toxins 2017, 9(2), 62; https://doi.org/10.3390/toxins9020062 - 10 Feb 2017

Cited by 78 | Viewed by 6840

Abstract

Future sustainability of freshwater resources is seriously threatened due to the presence of harmful cyanobacterial blooms, and yet, the number, extent, and distribution of most cyanobacterial toxins—including “emerging” toxins and other bioactive compounds—are poorly understood. We measured 15 cyanobacterial compounds—including four microcystins (MC), [...] Read more.

Future sustainability of freshwater resources is seriously threatened due to the presence of harmful cyanobacterial blooms, and yet, the number, extent, and distribution of most cyanobacterial toxins—including “emerging” toxins and other bioactive compounds—are poorly understood. We measured 15 cyanobacterial compounds—including four microcystins (MC), saxitoxin (SXT), cylindrospermopsin (CYL), anatoxin-a (ATX) and homo-anatoxin-a (hATX), two anabaenopeptins (Apt), three cyanopeptolins (Cpt), microginin (Mgn), and nodularin (NOD)—in six freshwater lakes that regularly experience noxious cHABs. MC, a human liver toxin, was present in all six lakes and was detected in 80% of all samples. Similarly, Apt, Cpt, and Mgn were detected in all lakes in roughly 86%, 50%, and 35% of all samples, respectively. Despite being a notable brackish water toxin, NOD was detected in the two shallowest lakes—Wingra (4.3 m) and Koshkonong (2.1 m). All compounds were highly variable temporally, and spatially. Metabolite profiles were significantly different between lakes suggesting lake characteristics influenced the cyanobacterial community and/or metabolite production. Understanding how cyanobacterial toxins are distributed across eutrophic lakes may shed light onto the ecological function of these metabolites, provide valuable information for their remediation and removal, and aid in the protection of public health. Full article

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

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Open AccessArticle

Patulin Degradation by the Biocontrol Yeast Sporobolomyces sp. Is an Inducible Process

by Giuseppe Ianiri, Cristina Pinedo, Alessandra Fratianni, Gianfranco Panfili and Raffaello Castoria

Toxins 2017, 9(2), 61; https://doi.org/10.3390/toxins9020061 - 10 Feb 2017

Cited by 45 | Viewed by 6628

Abstract

Patulin is a mycotoxin produced by Penicillium expansum and a common contaminant of pome fruits and their derived products worldwide. It is considered to be mutagenic, genotoxic, immunotoxic, teratogenic and cytotoxic, and the development of strategies to reduce this contamination is an active [...] Read more.

Patulin is a mycotoxin produced by Penicillium expansum and a common contaminant of pome fruits and their derived products worldwide. It is considered to be mutagenic, genotoxic, immunotoxic, teratogenic and cytotoxic, and the development of strategies to reduce this contamination is an active field of research. We previously reported that Sporobolomyces sp. is able to degrade patulin and convert it into the breakdown products desoxypatulinic acid and ascladiol, both of which were found to be less toxic than patulin. The specific aim of this study was the evaluation of the triggering of the mechanisms involved in patulin resistance and degradation by Sporobolomyces sp. Cells pre-incubated in the presence of a low patulin concentration showed a higher resistance to patulin toxicity and a faster kinetics of degradation. Similarly, patulin degradation was faster when crude intracellular protein extracts of Sporobolomyces sp. were prepared from cells pre-treated with the mycotoxin, indicating the induction of the mechanisms involved in the resistance and degradation of the mycotoxin by Sporobolomyces sp. This study contributes to the understanding of the mechanisms of patulin resistance and degradation by Sporobolomyces sp., which is an essential prerequisite for developing an industrial approach aiming at the production of patulin-free products. Full article

(This article belongs to the Special Issue Promising Detoxification Strategies to Mitigate Mycotoxins in Food and Feed)

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Open AccessReview

Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

by Wageha A. Awad, Claudia Hess and Michael Hess

Toxins 2017, 9(2), 60; https://doi.org/10.3390/toxins9020060 - 10 Feb 2017

Cited by 301 | Viewed by 15649

Abstract

Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as [...] Read more.

Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can utilize tight junction proteins as receptors for attachment and subsequent internalization, while others modify or destroy the tight junction proteins by different pathways and thereby provide a gateway to the underlying tissue. This review aims to deliver an overview of the tight junction structures and function, and its role in enteric bacterial pathogenesis with a special focus on chickens. A main conclusion will be that the molecular mechanisms used by enteric pathogens to disrupt epithelial barrier function in chickens needs a much better understanding, explicitly highlighted for Campylobacter jejuni, Salmonella enterica and Clostridium perfringens. This is a requirement in order to assist in discovering new strategies to avoid damages of the intestinal barrier or to minimize consequences from infections. Full article

(This article belongs to the Collection Leading Opinions (Closed))

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Open AccessArticle

Optimization for the Production of Deoxynivalenoland Zearalenone by Fusarium graminearum UsingResponse Surface Methodology

by Li Wu, Lijuan Qiu, Huijie Zhang, Juan Sun, Xuexu Hu and Bujun Wang

Toxins 2017, 9(2), 57; https://doi.org/10.3390/toxins9020057 - 10 Feb 2017

Cited by 23 | Viewed by 5246

Abstract

Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) are the most common contaminants in cereals worldwide, causing a wide range of adverse health effects on animals and humans. Many environmental factors can affect the production of these mycotoxins. Here, we have used response surface [...] Read more.

Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) are the most common contaminants in cereals worldwide, causing a wide range of adverse health effects on animals and humans. Many environmental factors can affect the production of these mycotoxins. Here, we have used response surface methodology (RSM) to optimize the Fusarium graminearum strain 29 culture conditions for maximal toxin production. Three factors, medium pH, incubation temperature and time, were optimized using a Box-Behnken design (BBD). The optimized conditions for DON production were pH 4.91 and an incubation temperature of 23.75 °C for 28 days, while maximal ZEN production required pH 9.00 and an incubation temperature of 15.05 °C for 28 days. The maximum levels of DON and ZEN production were 2811.17 ng/mL and 23789.70 ng/mL, respectively. Considering the total level of DON and ZEN, desirable yields of the mycotoxins were still obtained with medium pH of 6.86, an incubation temperature of 17.76 °C and a time of 28 days. The corresponding experimental values, from the validation experiments, fitted well with these predictions. This suggests that RSM could be used to optimize Fusarium mycotoxin levels, which are further purified for use as potential mycotoxin standards. Furthermore, it shows that acidic pH is a determinant for DON production, while an alkaline environment and lower temperature (approximately 15 °C) are favorable for ZEN accumulation. After extraction, separation and purification processes, the isolated mycotoxins were obtained through a simple purification process, with desirable yields, and acceptable purity. The mycotoxins could be used as potential analytical standards or chemical reagents for routine analysis. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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Open AccessArticle

Ustiloxin G, a New Cyclopeptide Mycotoxin from Rice False Smut Balls

by Xiaohan Wang, Jian Wang, Daowan Lai, Weixuan Wang, Jungui Dai, Ligang Zhou and Yang Liu

Toxins 2017, 9(2), 54; https://doi.org/10.3390/toxins9020054 - 10 Feb 2017

Cited by 65 | Viewed by 7883

Abstract

Ustiloxins were cyclopeptide mycotoxins from rice false smut balls (FSBs) that formed in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. To investigate the chemical diversity of these metabolites and their bioactivities, one new cyclopeptide, ustiloxin G (1), together [...] Read more.

Ustiloxins were cyclopeptide mycotoxins from rice false smut balls (FSBs) that formed in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. To investigate the chemical diversity of these metabolites and their bioactivities, one new cyclopeptide, ustiloxin G (1), together with four known congeners—ustiloxins A (2), B (3), D (4), and F (5)—were isolated from water extract of rice FSBs. Their structures were elucidated by analyses of their physical and spectroscopic data, including ultraviolet spectrometry (UV), infrared spectroscopy (IR), 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). All the compounds were evaluated for their cytotoxic as well as radicle and germ elongation inhibitory activities. Ustiloxin B (3) showed the best activity against the cell line BGC-823 with an IC₅₀ value of 1.03 µM, while ustiloxin G (1) showed moderate activity against the cell lines A549 and A375 with IC₅₀ values of 36.5 µM and 22.5 µM, respectively. Ustiloxins A (2), B (3), and G (1) showed strong inhibition of radicle and germ elongation of rice seeds. When their concentrations were at 200 µg/mL, the inhibitory ratios of radicle and germ elongation were more than 90% and 50%, respectively, the same effect as that of positive control (glyphosate). They also induced abnormal swelling of the roots and germs of rice seedlings. Full article

(This article belongs to the Section Mycotoxins)

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Open AccessArticle

Multi‐Mycotoxin Analysis in Durum Wheat Pasta by Liquid Chromatography Coupled to Quadrupole Orbitrap Mass Spectrometry

by Josefa Tolosa, Giulia Graziani, Anna Gaspari, Donato Chianese, Emilia Ferrer, Jordi Mañes and Alberto Ritieni

Toxins 2017, 9(2), 59; https://doi.org/10.3390/toxins9020059 - 9 Feb 2017

Cited by 45 | Viewed by 5605

Abstract

A simple and rapid multi‐mycotoxin method for the determination of 17 mycotoxins simultaneously is described in the present survey on durum and soft wheat pasta samples. Mycotoxins included in the study were those mainly reported in cereal samples: ochratoxin‐A (OTA), aflatoxin B1 (AFB1), [...] Read more.

A simple and rapid multi‐mycotoxin method for the determination of 17 mycotoxins simultaneously is described in the present survey on durum and soft wheat pasta samples. Mycotoxins included in the study were those mainly reported in cereal samples: ochratoxin‐A (OTA), aflatoxin B1 (AFB1), zearalenone (ZON), deoxynivalenol (DON), 3‐and 15‐acetyl‐deoxynivalenol (3‐AcDON and 15‐AcDON), nivalenol (NIV), neosolaniol (NEO), fusarenon‐X, (FUS‐X), T‐2 toxin (T‐2) and HT‐2 toxin (HT‐2), fumonisin B1 and B2 (FB1 and FB2), and four emerging mycotoxins: three enniatins (ENA, ENA1, and ENB), and beauvericin (BEA). Twenty‐nine samples were analyzed to provide an overview on mycotoxin presence: 27 samples of durum wheat pasta, and two samples of baby food. Analytical results concluded that trichothecenes showed the highest incidence, mainly DON, NIV, and HT‐2 toxin, followed by ZON and ENB, while NEO, FUS‐X, OTA, AFB1, and FUM were not detected in any sample. The highest contents corresponded to ENB and ranged from 91.15μg/kg to 710.90 μg/kg.
Full article

(This article belongs to the Special Issue Exposure and Risk Assessment for Mycotoxins)

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Open AccessArticle

Synthesis of Mono- and Di-Glucosides of Zearalenone and α-/β-Zearalenol by Recombinant Barley Glucosyltransferase HvUGT14077

by Herbert Michlmayr, Elisabeth Varga, Francesca Lupi, Alexandra Malachová, Christian Hametner, Franz Berthiller and Gerhard Adam

Toxins 2017, 9(2), 58; https://doi.org/10.3390/toxins9020058 - 9 Feb 2017

Cited by 25 | Viewed by 6550

Abstract

Zearalenone (ZEN) is an estrogenic mycotoxin occurring in Fusarium-infected cereals. Glucosylation is an important plant defense mechanism and generally reduces the acute toxicity of mycotoxins to humans and animals. Toxicological information about ZEN-glucosides is limited due to the unavailability of larger amounts [...] Read more.

Zearalenone (ZEN) is an estrogenic mycotoxin occurring in Fusarium-infected cereals. Glucosylation is an important plant defense mechanism and generally reduces the acute toxicity of mycotoxins to humans and animals. Toxicological information about ZEN-glucosides is limited due to the unavailability of larger amounts required for animal studies. HvUGT14077, a recently-validated ZEN-conjugating barley UDP-glucosyltransferase was expressed in Escherichia coli, affinity purified, and characterized. HvUGT14077 possesses high affinity (K_m = 3 µM) and catalytic efficiency (k_cat/K_m = 190 s⁻¹·mM⁻¹) with ZEN. It also efficiently glucosylates the phase-I ZEN-metabolites α-zearalenol and β-zearalenol, with k_cat/K_m of 40 and 74 s⁻¹·mM⁻¹, respectively. HvUGT14077 catalyzes O-glucosylation at C-14 and C-16 with preference of 14-glucoside synthesis. Furthermore, relatively slow consecutive formation of 14,16-di-glucosides was observed; their structures were tentatively identified by mass spectrometry and for ZEN-14,16-di-glucoside confirmed by nuclear magnetic resonance spectroscopy. Recombinant HvUGT14077 allowed efficient preparative synthesis of ZEN-glucosides, yielding about 90% ZEN-14-glucoside and 10% ZEN-16-glucoside. The yield of ZEN-16-glucoside could be increased to 85% by co-incubation with a β-glucosidase highly selective for ZEN-14-glucoside. Depletion of the co-substrate UDP-glucose was counteracted by a sucrose synthase based regeneration system. This strategy could also be of interest to increase the yield of minor glucosides synthesized by other glucosyltransferases. Full article

(This article belongs to the Section Mycotoxins)

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Open AccessArticle

Metabolism of Zearalenone and Its Major Modified Forms in Pigs

by Sabina B. Binder, Heidi E. Schwartz-Zimmermann, Elisabeth Varga, Gerlinde Bichl, Herbert Michlmayr, Gerhard Adam and Franz Berthiller

Toxins 2017, 9(2), 56; https://doi.org/10.3390/toxins9020056 - 8 Feb 2017

Cited by 124 | Viewed by 10317

Abstract

The Fusarium mycotoxin zearalenone (ZEN) can be conjugated with polar molecules, like sugars or sulfates, by plants and fungi. To date, the fate of these modified forms of ZEN has not yet been elucidated in animals. In order to investigate whether ZEN conjugates [...] Read more.

The Fusarium mycotoxin zearalenone (ZEN) can be conjugated with polar molecules, like sugars or sulfates, by plants and fungi. To date, the fate of these modified forms of ZEN has not yet been elucidated in animals. In order to investigate whether ZEN conjugates contribute to the total ZEN exposure of an individual, ZEN (10 µg/kg b.w.) and equimolar amounts of two of its plant metabolites (ZEN-14-O-β-glucoside, ZEN-16-O-β-glucoside) and of one fungal metabolite (ZEN-14-sulfate) were orally administered to four pigs as a single bolus using a repeated measures design. The concentrations of ZEN, its modified forms and its mammalian metabolites ZEN-14-glucuronide, α-zearalenol (α-ZEL) and α-ZEL-14-glucuronide in excreta were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) based methods. The biological recovery of ZEN in urine was 26% ± 10%, the total biological recovery in excreta was 40% ± 8%. Intact ZEN-14-sulfate, ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside were neither detected in urine nor in feces. After ZEN-14-sulfate application, 19% ± 5% of the administered dose was recovered in urine. In feces, no ZEN metabolites were detected. The total biological recoveries of ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside in the form of their metabolites in urine were 19% ± 11% and 13% ± 7%, respectively. The total biological recoveries in urine and feces amounted to 48% ± 7% and 34 ± 3%. An explanation for the low biological recoveries could be extensive metabolization by intestinal bacteria to yet unknown metabolites. In summary, ZEN-14-sulfate, ZEN-14-O-β-glucoside, and ZEN-16-O-β-glucoside were completely hydrolyzed in the gastrointestinal tract of swine, thus contributing to the overall toxicity of ZEN. Full article

(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)

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Open AccessArticle

Biodegradation Mechanisms of Patulin in Candida guilliermondii: An iTRAQ-Based Proteomic Analysis

by Yong Chen, Huai-Min Peng, Xiao Wang, Bo-Qiang Li, Man-Yuan Long and Shi-Ping Tian

Toxins 2017, 9(2), 48; https://doi.org/10.3390/toxins9020048 - 8 Feb 2017

Cited by 69 | Viewed by 6909

Abstract

Patulin, a potent mycotoxin, contaminates fruits and derived products worldwide, and is a serious health concern. Several yeast strains have shown the ability to effectively degrade patulin. However, the mechanisms of its biodegradation still remain unclear at this time. In the present study, [...] Read more.

Patulin, a potent mycotoxin, contaminates fruits and derived products worldwide, and is a serious health concern. Several yeast strains have shown the ability to effectively degrade patulin. However, the mechanisms of its biodegradation still remain unclear at this time. In the present study, biodegradation and involved mechanisms of patulin by an antagonistic yeast Candida guilliermondii were investigated. The results indicated that C. guilliermondii was capable of not only multiplying to a high population in medium containing patulin, but also effectively reducing patulin content in culture medium. Degradation of patulin by C. guilliermondii was dependent on the yeast cell viability, and mainly occurred inside cells. E-ascladiol was the main degradation product of patulin. An iTRAQ-based proteomic analysis revealed that the responses of C. guilliermondii to patulin were complex. A total of 30 differential proteins involved in 10 biological processes were identified, and more than two-thirds of the differential proteins were down-accumulated. Notably, a short-chain dehydrogenase (gi|190348612) was markedly induced by patulin at both the protein and mRNA levels. Our findings will provide a foundation to help enable the commercial development of an enzyme formulation for the detoxification of patulin in fruit-derived products. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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Open AccessEditorial

Toxins: State of the Journal Report, 2017

by Chao Xiao and Vernon L. Tesh

Toxins 2017, 9(2), 55; https://doi.org/10.3390/toxins9020055 - 4 Feb 2017

Viewed by 4925

Abstract

On behalf of the Toxins editorial team, we are happy to report that the impact factor for Toxins for 2015 is 3.571, 5-year impact factor: 3.942, which places the journal at a ranking of 16th out of 89 journals covering the field of [...] Read more.

On behalf of the Toxins editorial team, we are happy to report that the impact factor for Toxins for 2015 is 3.571, 5-year impact factor: 3.942, which places the journal at a ranking of 16th out of 89 journals covering the field of toxicology. [...] Full article

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Open AccessReview

Deoxynivalenol Exposure in Norway, Risk Assessments for Different Human Age Groups

by Leif Sundheim, Inger Therese Lillegaard, Christiane Kruse Fæste, Anne-Lise Brantsæter, Guro Brodal and Gunnar Sundstøl Eriksen

Toxins 2017, 9(2), 46; https://doi.org/10.3390/toxins9020046 - 4 Feb 2017

Cited by 40 | Viewed by 6086

Abstract

Deoxynivalenol (DON) is the most common mycotoxin in Norwegian cereals, and DON is detected in most samples of crude cereal grain and cereal food commodities such as flour, bran, and oat flakes. The Norwegian Scientific Committee for Food Safety assessed the risk for [...] Read more.

Deoxynivalenol (DON) is the most common mycotoxin in Norwegian cereals, and DON is detected in most samples of crude cereal grain and cereal food commodities such as flour, bran, and oat flakes. The Norwegian Scientific Committee for Food Safety assessed the risk for adverse effects of deoxynivalenol (DON) in different age groups of the domestic population. This review presents the main results from the risk assessment, supplemented with some recently published data. Impairment of the immune system together with reduced feed intake and weight gain are the critical effects of DON in experimental animals on which the current tolerable daily intake was established. Based on food consumption and occurrence data, the mean exposure to DON in years with low and high levels of DON in the flour, respectively, were in the range of or up to two times the Tolerable Daily Intake (TDI) in 1-year-old infants and 2-year-old children. In years with high mean DON concentration, the high (95th-percentile) exposure exceeded the TDI by up to 3.5 times in 1-, 2- , 4-, and 9-year-old children. The assessment concluded that exceeding the TDI in infants and children is of concern. The estimated dietary DON intakes in adolescent and adult populations are in the range of the TDI or below, and are not a health concern. Acute human exposure to DON is not of concern in any age group. Full article

(This article belongs to the Special Issue Exposure and Risk Assessment for Mycotoxins)

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Open AccessReview

Protection against Shiga Toxins

by Simona Kavaliauskiene, Anne Berit Dyve Lingelem, Tore Skotland and Kirsten Sandvig

Toxins 2017, 9(2), 44; https://doi.org/10.3390/toxins9020044 - 3 Feb 2017

Cited by 47 | Viewed by 10090

Abstract

Shiga toxins consist of an A-moiety and five B-moieties able to bind the neutral glycosphingolipid globotriaosylceramide (Gb3) on the cell surface. To intoxicate cells efficiently, the toxin A-moiety has to be cleaved by furin and transported retrogradely to the Golgi apparatus and to [...] Read more.

Shiga toxins consist of an A-moiety and five B-moieties able to bind the neutral glycosphingolipid globotriaosylceramide (Gb3) on the cell surface. To intoxicate cells efficiently, the toxin A-moiety has to be cleaved by furin and transported retrogradely to the Golgi apparatus and to the endoplasmic reticulum. The enzymatically active part of the A-moiety is then translocated to the cytosol, where it inhibits protein synthesis and in some cell types induces apoptosis. Protection of cells can be provided either by inhibiting binding of the toxin to cells or by interfering with any of the subsequent steps required for its toxic effect. In this article we provide a brief overview of the interaction of Shiga toxins with cells, describe some compounds and conditions found to protect cells against Shiga toxins, and discuss whether they might also provide protection in animals and humans. Full article

(This article belongs to the Special Issue Novel Pharmacological Inhibitors for Bacterial Protein Toxins)

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Open AccessFeature PaperReview

p-Cresyl Sulfate

by Tessa Gryp, Raymond Vanholder, Mario Vaneechoutte and Griet Glorieux

Toxins 2017, 9(2), 52; https://doi.org/10.3390/toxins9020052 - 29 Jan 2017

Cited by 273 | Viewed by 16016

Abstract

If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological [...] Read more.

If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden. Full article

(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)

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Open AccessArticle

Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by Escherichia coli O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model

by Rodney A. Moxley, David H. Francis, Mizuho Tamura, David B. Marx, Kristina Santiago-Mateo and Mojun Zhao

Toxins 2017, 9(2), 49; https://doi.org/10.3390/toxins9020049 - 26 Jan 2017

Cited by 18 | Viewed by 5491

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal [...] Read more.

Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 × 10⁹ colony-forming units of EHEC O157:H7 strain EDL933 (Stx1⁺, Stx2⁺) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally administered placebo or TMA-15 (0.3, 1.0 or 3.0 mg/kg body weight). Compared to placebo (n = 10), TMA-15 (n = 35) yielded a significantly greater probability of survival, length of survival, and weight gain (p <0.05). The efficacy of TMA-15 against brain lesions and death was 62.9% (p = 0.0004) and 71.4% (p = 0.0004), respectively. These results suggest that TMA-15 may potentially prevent or reduce vascular necrosis and infarction of the brain attributable to Stx2 in human patients acutely infected with EHEC. However, we do not infer that TMA-15 treatment will completely protect human patients infected with EHEC O157:H7 strains that produce both Stx1 and Stx2. Full article

(This article belongs to the Collection Shiga Toxins)

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Open AccessArticle

Functional Elucidation of Nemopilema nomurai and Cyanea nozakii Nematocyst Venoms’ Lytic Activity Using Mass Spectrometry and Zymography

by Yang Yue, Huahua Yu, Rongfeng Li, Ronge Xing, Song Liu, Kecheng Li, Xueqin Wang, Xiaolin Chen and Pengcheng Li

Toxins 2017, 9(2), 47; https://doi.org/10.3390/toxins9020047 - 26 Jan 2017

Cited by 24 | Viewed by 6842

Abstract

Background: Medusozoans utilize explosively discharging penetrant nematocysts to inject venom into prey. These venoms are composed of highly complex proteins and peptides with extensive bioactivities, as observed in vitro. Diverse enzymatic toxins have been putatively identified in the venom of jellyfish, Nemopilema nomurai [...] Read more.

Background: Medusozoans utilize explosively discharging penetrant nematocysts to inject venom into prey. These venoms are composed of highly complex proteins and peptides with extensive bioactivities, as observed in vitro. Diverse enzymatic toxins have been putatively identified in the venom of jellyfish, Nemopilema nomurai and Cyanea nozakii, through examination of their proteomes and transcriptomes. However, functional examination of putative enzymatic components identified in proteomic approaches to elucidate potential bioactivities is critically needed. Methods: In this study, enzymatic toxins were functionally identified using a combined approach consisting of in gel zymography and liquid chromatography tandem mass spectrometry (LC-MS/MS). The potential roles of metalloproteinases and lipases in hemolytic activity were explored using specific inhibitors. Results: Zymography indicated that nematocyst venom possessed protease-, lipase- and hyaluronidase-class activities. Further, proteomic approaches using LC-MS/MS indicated sequence homology of proteolytic bands observed in zymography to extant zinc metalloproteinase-disintegrins and astacin metalloproteinases. Moreover, pre-incubation of the metalloproteinase inhibitor batimastat with N. nomurai nematocyst venom resulted in an approximate 62% reduction of hemolysis compared to venom exposed sheep erythrocytes, suggesting that metalloproteinases contribute to hemolytic activity. Additionally, species within the molecular mass range of 14–18 kDa exhibited both egg yolk and erythrocyte lytic activities in gel overlay assays. Conclusion: For the first time, our findings demonstrate the contribution of jellyfish venom metalloproteinase and suggest the involvement of lipase species to hemolytic activity. Investigations of this relationship will facilitate a better understanding of the constituents and toxicity of jellyfish venom. Full article

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

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Open AccessArticle

Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction

by Vania C. Liuzzi, Valentina Mirabelli, Maria Teresa Cimmarusti, Miriam Haidukowski, John F. Leslie, Antonio F. Logrieco, Rocco Caliandro, Francesca Fanelli and Giuseppina Mulè

Toxins 2017, 9(2), 45; https://doi.org/10.3390/toxins9020045 - 25 Jan 2017

Cited by 65 | Viewed by 7900

Abstract

Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-l-methionine-dependent N-methyltransferase activities. [...] Read more.

Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-l-methionine-dependent N-methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s) enabling these differential metabolic profiles is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA production by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa) analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing profiles and ESYN1 three-dimensional structures. Structural differences in the β strand’s Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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Open AccessArticle

Involvement of FvSet1 in Fumonisin B1 Biosynthesis, Vegetative Growth, Fungal Virulence, and Environmental Stress Responses in Fusarium verticillioides

by Qin Gu, Hafiz Abdul Samad Tahir, Hao Zhang, Hai Huang, Tiantian Ji, Xiao Sun, Liming Wu, Huijun Wu and Xuewen Gao

Toxins 2017, 9(2), 43; https://doi.org/10.3390/toxins9020043 - 24 Jan 2017

Cited by 31 | Viewed by 6291

Abstract

Fusarium verticillioides (teleomorph, Gibberella moniliformis) is an important plant pathogen that causes seedling blight, stalk rot, and ear rot in maize (Zea mays). During infection, F. verticillioides produce fumonsins B1 (FB1) that pose a serious threat to human and animal [...] Read more.

Fusarium verticillioides (teleomorph, Gibberella moniliformis) is an important plant pathogen that causes seedling blight, stalk rot, and ear rot in maize (Zea mays). During infection, F. verticillioides produce fumonsins B1 (FB1) that pose a serious threat to human and animal health. Recent studies showed that Set1, a methyltransferase of H3K4, was responsible for toxin biosynthesis in filamentous fungi. However, to date, the regulation of FvSet1 on FB1 biosynthesis remains unclear. In the current study, we identified only one Set1 ortholog in F. verticillioides (FvSet1) and found that the deletion of FvSET1 led to various defects in fungal growth and pathogenicity. More interestingly, the FvSET1 deletion mutant (ΔFvSet1) showed a significant defect in FB1 biosynthesis and lower expression levels of FUM genes. FvSet1 was also found to play an important role in the responses of F. verticillioides to multiple environmental stresses via regulating the phosphorylation of FvMgv1 and FvHog1. Taken together, these results indicate that FvSet1 plays essential roles in the regulation of FB1 biosynthesis, fungal growth and virulence, as well as various stress responses in F. verticillioides. Full article

(This article belongs to the Special Issue Selected papers from 1^st China Mycotoxin Conference: Current trends in mycotoxin prevention and control)

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