Toxins

18 pages, 647 KiB

Open AccessEditor’s ChoiceReview

Repertoire of the Bacillus thuringiensis Virulence Factors Unrelated to Major Classes of Protein Toxins and Its Role in Specificity of Host-Pathogen Interactions

by Yury V. Malovichko, Anton A. Nizhnikov and Kirill S. Antonets

Toxins 2019, 11(6), 347; https://doi.org/10.3390/toxins11060347 - 17 Jun 2019

Cited by 46 | Viewed by 7309

Abstract

Bacillus thuringiensis (Bt) is a Gram-positive soil bacteria that infects invertebrates, predominantly of Arthropoda phylum. Due to its immense host range Bt has become a leading producer of biopesticides applied both in biotechnology and agriculture. Cytotoxic effect of Bt, as [...] Read more.

Bacillus thuringiensis (Bt) is a Gram-positive soil bacteria that infects invertebrates, predominantly of Arthropoda phylum. Due to its immense host range Bt has become a leading producer of biopesticides applied both in biotechnology and agriculture. Cytotoxic effect of Bt, as well as its host specificity, are commonly attributed either to proteinaceous crystal parasporal toxins (Cry and Cyt) produced by bacteria in a stationary phase or to soluble toxins of Vip and Sip families secreted by vegetative cells. At the same time, numerous non-toxin virulence factors of Bt have been discovered, including metalloproteases, chitinases, aminopolyol antibiotics and nucleotide-mimicking moieties. These agents act at each stage of the B. thuringiensis invasion and contribute to cytotoxic properties of Bt strains enhancing toxin activity, ensuring host immune response evasion and participating in extracellular matrix degeneration. In this review we attempt to classify Bt virulence factors unrelated to major groups of protein toxins and discuss their putative role in the establishment of Bt specificity to various groups of insects. Full article

(This article belongs to the Special Issue Insecticidal Toxins: Advances in Discovery and PestControl Applications)

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15 pages, 2937 KiB

Open AccessEditor’s ChoiceArticle

Toxin B Variants from Clostridium difficile Strains VPI 10463 and NAP1/027 Share Similar Substrate Profile and Cellular Intoxication Kinetics but Use Different Host Cell Entry Factors

by Diana López-Ureña, Josué Orozco-Aguilar, Yendry Chaves-Madrigal, Andrea Ramírez-Mata, Amanda Villalobos-Jimenez, Stefan Ost, Carlos Quesada-Gómez, César Rodríguez, Panagiotis Papatheodorou and Esteban Chaves-Olarte

Toxins 2019, 11(6), 348; https://doi.org/10.3390/toxins11060348 - 17 Jun 2019

Cited by 27 | Viewed by 5062

Abstract

Clostridium difficile induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdB_NAP1 [...] Read more.

Clostridium difficile induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdB_NAP1 with that by the reference strain VPI 10463 (TcdB_VPI). In a mouse ligated intestinal loop model, TcdB_NAP1 induced higher neutrophil recruitment, cytokine release, and epithelial damage than TcdB_VPI. Both toxins modified the same panel of small GTPases and exhibited similar in vitro autoprocessing kinetics. On the basis of sequence variations in the frizzled-binding domain (FBD), we reasoned that TcdB_VPI and TcdB_NAP1 might have different receptor specificities. To test this possibility, we used a TcdB from a NAP1 variant strain (TcdB_NAP1v) unable to glucosylate RhoA but with the same receptor-binding domains as TcdB_NAP1. Cells were preincubated with TcdB_NAP1v to block cellular receptors, prior to intoxication with either TcdB_VPI or TcdB_NAP1. Preincubation with TcdB_NAP1v blocked RhoA glucosylation by TcdB_NAP1 but not by TcdB_VPI, indicating that the toxins use different host factors for cell entry. This crucial difference might explain the increased biological activity of TcdB_NAP1 in the intestine, representing a contributing factor for the increased virulence of the NAP1/027 strain. Full article

(This article belongs to the Special Issue Toxins Secretion and Translocation)

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22 pages, 2308 KiB

Open AccessEditor’s ChoiceArticle

Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus

by Rebecca A. Keogh, Rachel L. Zapf, Emily Trzeciak, Gillian G. Null, Richard E. Wiemels and Ronan K. Carroll

Toxins 2019, 11(6), 343; https://doi.org/10.3390/toxins11060343 - 16 Jun 2019

Cited by 12 | Viewed by 6370

Abstract

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of [...] Read more.

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PpiB and PrsA) that are involved in the regulation of virulence determinants and have shown that PpiB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a ppiB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the ppiB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a ppiB mutant strain has reduced levels of the phenol-soluble modulins and that both ppiB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PpiB and PrsA. Results suggest a novel role for PpiB in S. aureus protein secretion. Collectively, our results demonstrate that PpiB and PrsA influence S. aureus toxins via distinct mechanisms, and that PpiB but not PrsA contributes to disease. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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13 pages, 842 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of Mycotoxins in Swine Feeding from Spain

by Natalia Arroyo-Manzanares, Vicente Rodríguez-Estévez, Plácido Arenas-Fernández, Ana M. García-Campaña and Laura Gámiz-Gracia

Toxins 2019, 11(6), 342; https://doi.org/10.3390/toxins11060342 - 15 Jun 2019

Cited by 40 | Viewed by 5627

Abstract

A survey including 228 pig feed samples from Spain has been developed, exploring the occurrence of 19 mycotoxins (aflatoxins B1, B2, G1 and G2, ochratoxin A, fumonisins B1 and B2, citrinin, zearalenone, deoxynivalenol, fusarenon X, sterigmatocystin, T-2 toxin, HT-2 toxin, enniatins A, A1, [...] Read more.

A survey including 228 pig feed samples from Spain has been developed, exploring the occurrence of 19 mycotoxins (aflatoxins B1, B2, G1 and G2, ochratoxin A, fumonisins B1 and B2, citrinin, zearalenone, deoxynivalenol, fusarenon X, sterigmatocystin, T-2 toxin, HT-2 toxin, enniatins A, A1, B and B2, and beauvericin). The samples were analysed by solid-liquid extraction followed by liquid chromatography coupled with fluorescence or mass spectrometry detection. Enniatin B was found in 100% of the samples (up to 1200 µg/kg) and beauvericin in more than 90%. Moreover, 40% of samples were contaminated with more than five mycotoxins. This high occurrence is insurmountable and surpasses all previous studies, probably due to the inclusion of emerging mycotoxins, scarcely explored. The majority of the samples (96.9%) were in accordance with EU regulations, which do not address emerging mycotoxins or co-occurrence. These results show that in order to ensure mycotoxin absence, emerging mycotoxins should always be considered. Full article

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

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21 pages, 3599 KiB

Open AccessEditor’s ChoiceArticle

Rational Design of Toxoid Vaccine Candidates for Staphylococcus aureus Leukocidin AB (LukAB)

by Shweta Kailasan, Thomas Kort, Ipsita Mukherjee, Grant C. Liao, Tulasikumari Kanipakala, Nils Williston, Nader Ganjbaksh, Arundhathi Venkatasubramaniam, Frederick W. Holtsberg, Hatice Karauzum, Rajan P. Adhikari and M. Javad Aman

Toxins 2019, 11(6), 339; https://doi.org/10.3390/toxins11060339 - 14 Jun 2019

Cited by 17 | Viewed by 5382

Abstract

Staphylococcus aureus (SA) infections cause high mortality and morbidity in humans. Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins. While all vaccine development efforts that aimed at achieving opsonophagocytic [...] Read more.

Staphylococcus aureus (SA) infections cause high mortality and morbidity in humans. Being central to its pathogenesis, S. aureus thwarts the host defense by secreting a myriad of virulence factors, including bicomponent, pore-forming leukotoxins. While all vaccine development efforts that aimed at achieving opsonophagocytic killing have failed, targeting virulence by toxoid vaccines represents a novel approach to preventing mortality and morbidity that are caused by SA. The recently discovered leukotoxin LukAB kills human phagocytes and monocytes and it is present in all known S. aureus clinical isolates. While using a structure-guided approach, we generated a library of mutations that targeted functional domains within the LukAB heterodimer to identify attenuated toxoids as potential vaccine candidates. The mutants were evaluated based on expression, solubility, yield, biophysical properties, cytotoxicity, and immunogenicity, and several fully attenuated LukAB toxoids that were capable of eliciting high neutralizing antibody titers were identified. Rabbit polyclonal antibodies against the lead toxoid candidate provided potent neutralization of LukAB. While the neutralization of LukAB alone was not sufficient to fully suppress leukotoxicity in supernatants of S. aureus USA300 isolates, a combination of antibodies against LukAB, α-toxin, and Panton-Valentine leukocidin completely neutralized the cytotoxicity of these strains. These data strongly support the inclusion of LukAB toxoids in a multivalent toxoid vaccine for the prevention of S. aureus disease. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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11 pages, 2322 KiB

Open AccessEditor’s ChoiceArticle

Detection and Spatio-Temporal Distribution of Pinnatoxins in Shellfish from the Atlantic and Cantabrian Coasts of Spain

by J. Pablo Lamas, Fabiola Arévalo, Ángeles Moroño, Jorge Correa, Susana Muñíz and Juan Blanco

Toxins 2019, 11(6), 340; https://doi.org/10.3390/toxins11060340 - 14 Jun 2019

Cited by 30 | Viewed by 3295

Abstract

For the first time, pinnatoxins have been detected in shellfish from the Atlantic and Cantabrian coasts of Spain. High sensitivity LC-MS/MS systems were used to monitor all the currently known pinnatoxins (A–H). Pinnatoxin G (PnTX G) was the most prevalent toxin of the [...] Read more.

For the first time, pinnatoxins have been detected in shellfish from the Atlantic and Cantabrian coasts of Spain. High sensitivity LC-MS/MS systems were used to monitor all the currently known pinnatoxins (A–H). Pinnatoxin G (PnTX G) was the most prevalent toxin of the group, but its metabolite PnTX A has also been found at much lower levels. No trend in PnTX G concentration was found in the area, but a hotspot in the Ría de Camariñas has been identified. The maximum concentrations found did not exceed 15 µg·kg⁻¹, being, in most cases, below 3 µg·kg⁻¹. The highest concentrations were found in wild (intertidal) populations of mussels which attained much higher levels than raft-cultured ones, suggesting that the toxin-producer organisms preferentially develop in shallow areas. Other bivalve species had, in general, lower concentrations. The incidence of PnTX G followed a seasonal pattern in which the maximum concentrations took place in winter months. PnTX G was found to be partially esterified but the esterification percentage was not high (lower than 30%). Full article

(This article belongs to the Special Issue Dinoflagellate Toxins)

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14 pages, 1275 KiB

Open AccessEditor’s ChoiceArticle

Cytotoxicity, Genotoxicity and Disturbance of Cell Cycle in HepG2 Cells Exposed to OTA and BEA: Single and Combined Actions

by Ana Juan-García, Josefa Tolosa, Cristina Juan and María-José Ruiz

Toxins 2019, 11(6), 341; https://doi.org/10.3390/toxins11060341 - 14 Jun 2019

Cited by 55 | Viewed by 4906

Abstract

Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study [...] Read more.

Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study was to determine their combination effect in HepG2 cells, presented for the first time. In this study, the type of interaction among BEA and OTA through an isobologram method, cell cycle disturbance by flow cytometry, and genotoxic potential by in vitro micronucleus (MN) assay following the TG 487 (OECD, 2016) of BEA and OTA individually and combined in HepG2 cells are presented. Cytotoxic concentration ranges studied by the MTT assay over 24, 48, and 72 h were from 0 to 25 µM for BEA and from 0 to 100 µM for OTA, while BEA + OTA combinations were at a 1:10 ratio from 3.4 to 27.5 µM. The toxicity observed for BEA was higher than for OTA at all times assayed; additive and synergistic effects were detected for their mixtures. Cell cycle arrest in the G0/G1 phase was detected for OTA and BEA + OTA treatments in HepG2 cells. Genotoxicity revealed significant effects for BEA, OTA, and in combinations underlining the importance of studying real exposure scenarios of chronic exposure to mycotoxins. Full article

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

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23 pages, 4870 KiB

Open AccessEditor’s ChoiceArticle

Effects of Dietary Zearalenone on Oxidative Stress, Cell Apoptosis, and Tight Junction in the Intestine of Juvenile Grass Carp (Ctenopharyngodon idella)

by Ya-Li Wang, Xiao-Qiu Zhou, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Shang-Wen Wang, Sheng-Yao Kuang, Ling Tang and Lin Feng

Toxins 2019, 11(6), 333; https://doi.org/10.3390/toxins11060333 - 12 Jun 2019

Cited by 41 | Viewed by 5457

Abstract

Zearalenone (ZEA) is a prevalent mycotoxin with high toxicity in animals. In order to study its effect on juvenile grass carp (Ctenopharyngodon idella), six diets supplemented with different levels of ZEA (0, 535, 1041, 1548, 2002, and 2507 μg/kg diet) for [...] Read more.

Zearalenone (ZEA) is a prevalent mycotoxin with high toxicity in animals. In order to study its effect on juvenile grass carp (Ctenopharyngodon idella), six diets supplemented with different levels of ZEA (0, 535, 1041, 1548, 2002, and 2507 μg/kg diet) for 10 weeks were studied to assess its toxicity on intestinal structural integrity and potential mechanisms of action. Our report firstly proved that ZEA led to growth retardation and body deformity, and impaired the intestinal structural integrity of juvenile grass carp, as revealed by the following findings: (1) ZEA accumulated in the intestine and caused histopathological lesions; (2) ZEA resulted in oxidative injury, apoptosis, and breached tight junctions in the fish intestine, which were probably associated with Nuclear factor-erythroid 2-related factor 2 (Nrf2), p38 mitogen activated protein kinases (p38MAPK), and myosin light chain kinase (MLCK) signaling pathways, respectively. ZEA had no influence on the antioxidant gene levels of Kelch-like ECH associating protein 1 (Keap1)b (rather than Keap1a), glutathione-S-transferase (GST)P1, GSTP2 (not in the distal intestine (DI)), tight junctions occludin, claudin-c (not in the proximal intestine (PI)), or claudin-3c (not in the mid intestine (MI) or DI). Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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20 pages, 639 KiB

Open AccessEditor’s ChoiceReview

Rural Subsistence Maize Farming in South Africa: Risk Assessment and Intervention models for Reduction of Exposure to Fumonisin Mycotoxins

by Johanna Alberts, John Rheeder, Wentzel Gelderblom, Gordon Shephard and Hester-Mari Burger

Toxins 2019, 11(6), 334; https://doi.org/10.3390/toxins11060334 - 12 Jun 2019

Cited by 32 | Viewed by 6076

Abstract

Maize is a staple crop in rural subsistence regions of southern Africa, is mainly produced for direct household consumption and is often contaminated with high levels of mycotoxins. Chronic exposure to mycotoxins is a risk factor for human diseases as it is implicated [...] Read more.

Maize is a staple crop in rural subsistence regions of southern Africa, is mainly produced for direct household consumption and is often contaminated with high levels of mycotoxins. Chronic exposure to mycotoxins is a risk factor for human diseases as it is implicated in the development of cancer, neural tube defects as well as stunting in children. Although authorities may set maximum levels, these regulations are not effective in subsistence farming communities. As maize is consumed in large quantities, exposure to mycotoxins will surpass safe levels even where the contamination levels are below the regulated maximum levels. It is clear that the lowering of exposure in these communities requires an integrated approach. Detailed understanding of agricultural practices, mycotoxin occurrence, climate change/weather patterns, human exposure and risk are warranted to guide adequate intervention programmes. Risk communication and creating awareness in affected communities are also critical. A range of biologically based products for control of mycotoxigenic fungi and mycotoxins in maize have been developed and commercialised. Application of these methods is limited due to a lack of infrastructure and resources. Other challenges regarding integration and sustainability of technological and community-based mycotoxin reduction strategies include (i) food security, and (ii) the traditional use of mouldy maize. Full article

(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)

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12 pages, 1593 KiB

Open AccessEditor’s ChoiceArticle

Rapid Purification of Endotoxin-Free RTX Toxins

by Ondrej Stanek, Jiri Masin, Radim Osicka, David Jurnecka, Adriana Osickova and Peter Sebo

Toxins 2019, 11(6), 336; https://doi.org/10.3390/toxins11060336 - 12 Jun 2019

Cited by 17 | Viewed by 5163

Abstract

Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS). Due to low yields and poor stability in cultures of the original pathogens, it is useful to purify recombinant [...] Read more.

Cytolytic leukotoxins of the repeat in toxin (RTX) family are large proteins excreted by gram-negative bacterial pathogens through the type 1 secretion system (T1SS). Due to low yields and poor stability in cultures of the original pathogens, it is useful to purify recombinant fatty-acylated RTX cytolysins from inclusion bodies produced in E. coli. Such preparations are, however, typically contaminated by high amounts of E. coli lipopolysaccharide (LPS or endotoxin). We report a simple procedure for purification of large amounts of biologically active and endotoxin-free RTX toxins. It is based on the common feature of RTX cytolysins that are T1SS-excreted as unfolded polypeptides and fold into a biologically active toxin only upon binding of calcium ions outside of the bacterial cell. Mimicking this process, the RTX proteins are solubilized from inclusion bodies with buffered 8 M urea, bound onto a suitable chromatographic medium under denaturing conditions and the contaminating LPS is removed through extensive on-column washes with buffers containing 6 to 8 M urea and 1% Triton X-100 or Triton X-114. Extensive on-column rinsing with 8 M urea buffer removes residual detergent and the eluted highly active RTX protein preparations then contain only trace amounts of LPS. The procedure is exemplified using four prototypic RTX cytolysins, the Bordetella pertussis CyaA and the hemolysins of Escherichia coli (HlyA), Kingella kingae (RtxA), and Actinobacillus pleuropneumoniae (ApxIA). Full article

(This article belongs to the Special Issue RTX Toxins)

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29 pages, 1731 KiB

Open AccessEditor’s ChoiceReview

The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections

by Patience Shumba, Srikanth Mairpady Shambat and Nikolai Siemens

Toxins 2019, 11(6), 332; https://doi.org/10.3390/toxins11060332 - 11 Jun 2019

Cited by 33 | Viewed by 11218

Abstract

Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both [...] Read more.

Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Full article

(This article belongs to the Special Issue Immunotherapies and Vaccines against Diseases Caused by Staphylococcal Toxins)

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10 pages, 933 KiB

Open AccessEditor’s ChoiceArticle

Occurrence of the Ochratoxin A Degradation Product 2′R-Ochratoxin A in Coffee and Other Food: An Update

by Franziska Sueck, Vanessa Hemp, Jonas Specht, Olga Torres, Benedikt Cramer and Hans-Ulrich Humpf

Toxins 2019, 11(6), 329; https://doi.org/10.3390/toxins11060329 - 8 Jun 2019

Cited by 30 | Viewed by 5150

Abstract

Food raw materials can contain the mycotoxin ochratoxin A (OTA). Thermal processing of these materials may result in decreased OTA levels but also in the formation of the thermal isomerization product 2′R-ochratoxin A (2′R-OTA). So far, only 2′R-OTA levels reported from 15 coffee [...] Read more.

Food raw materials can contain the mycotoxin ochratoxin A (OTA). Thermal processing of these materials may result in decreased OTA levels but also in the formation of the thermal isomerization product 2′R-ochratoxin A (2′R-OTA). So far, only 2′R-OTA levels reported from 15 coffee samples in 2008 are known, which is little when compared to the importance of coffee as a food and trading good. Herein, we present results from a set of model experiments studying the effect of temperatures between 120 °C and 270 °C on the isomerization of OTA to 2′R-OTA. It is shown that isomerization of OTA starts at temperatures as low as 120 °C. At 210 °C and above, the formation of 25% 2′R-OTA is observed in less than one minute. Furthermore, 51 coffee samples from France, Germany, and Guatemala were analyzed by HPLC-MS/MS for the presence of OTA and 2′R-OTA. OTA was quantified in 96% of the samples, while 2′R-OTA was quantifiable in 35% of the samples. The highest OTA and 2′R-OTA levels of 28.4 µg/kg and 3.9 µg/kg, respectively, were detected in coffee from Guatemala. The OTA:2′R-OTA ratio in the samples ranged between 2.5:1 and 10:1 and was on average 5.5:1. Besides coffee, 2′R-OTA was also for the first time detected in a bread sample and malt coffee powder. Full article

(This article belongs to the Special Issue Fate of Free, “Masked” and Conjugated/Modified forms of Mycotoxins)

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11 pages, 678 KiB

Open AccessEditor’s ChoiceArticle

Application of Zearalenone (ZEN)-Detoxifying Bacillus in Animal Feed Decontamination through Fermentation

by Shiau-Wei Chen, Han-Tsung Wang, Wei-Yuan Shih, Yan-An Ciou, Yu-Yi Chang, Laurensia Ananda, Shu-Yin Wang and Jih-Tay Hsu

Toxins 2019, 11(6), 330; https://doi.org/10.3390/toxins11060330 - 8 Jun 2019

Cited by 30 | Viewed by 4540

Abstract

Zearalenone (ZEN) is an estrogenic mycotoxin which can cause loss in animal production. The aim of this study was to screen Bacillus strains for their ZEN detoxification capability and use a fermentation process to validate their potential application in the feed industry. In [...] Read more.

Zearalenone (ZEN) is an estrogenic mycotoxin which can cause loss in animal production. The aim of this study was to screen Bacillus strains for their ZEN detoxification capability and use a fermentation process to validate their potential application in the feed industry. In the high-level ZEN-contaminated maize (5 mg·kg⁻¹) fermentation test, B2 strain exhibited the highest detoxification rate, removing 56% of the ZEN. However, B2 strain was not the strain with the highest ZEN detoxification in the culturing media. When B2 grew in TSB medium with ZEN, it had higher bacterial numbers, lactic acid, acetic acid, total volatile fatty acids, and ammonia nitrogen. The ZEN-contaminated maize fermented by B2 strain had better fermentation characteristics (lactic acid > 110 mmol·L⁻¹; acetic acid < 20 mmol·L⁻¹; pH < 4.5) than ZEN-free maize. Furthermore, B2 also had detoxification capabilities toward aflatoxins B1, deoxynivalenol, fumonisin B1, and T2 toxin. Our study demonstrated differences in screening outcome between bacterial culturing conditions and the maize fermentation process. This is important for the feed industry to consider when choosing a proper method to screen candidate isolates for the pretreatment of ZEN-contaminated maize. It appears that using the fermentation process to address the ZEN-contaminated maize problem in animal feed is a reliable choice. Full article

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

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23 pages, 484 KiB

Open AccessEditor’s ChoiceReview

Fumonisins: Impact on Agriculture, Food, and Human Health and their Management Strategies

by Madhu Kamle, Dipendra K. Mahato, Sheetal Devi, Kyung Eun Lee, Sang G. Kang and Pradeep Kumar

Toxins 2019, 11(6), 328; https://doi.org/10.3390/toxins11060328 - 7 Jun 2019

Cited by 221 | Viewed by 15142

Abstract

The fumonisins producing fungi, Fusarium spp., are ubiquitous in nature and contaminate several food matrices that pose detrimental health hazards on humans as well as on animals. This has necessitated profound research for the control and management of the toxins to guarantee better [...] Read more.

The fumonisins producing fungi, Fusarium spp., are ubiquitous in nature and contaminate several food matrices that pose detrimental health hazards on humans as well as on animals. This has necessitated profound research for the control and management of the toxins to guarantee better health of consumers. This review highlights the chemistry and biosynthesis process of the fumonisins, their occurrence, effect on agriculture and food, along with their associated health issues. In addition, the focus has been put on the detection and management of fumonisins to ensure safe and healthy food. The main focus of the review is to provide insights to the readers regarding their health-associated food consumption and possible outbreaks. Furthermore, the consumers’ knowledge and an attempt will ensure food safety and security and the farmers’ knowledge for healthy agricultural practices, processing, and management, important to reduce the mycotoxin outbreaks due to fumonisins. Full article

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

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16 pages, 11729 KiB

Open AccessEditor’s ChoiceReview

Ricin: An Ancient Story for a Timeless Plant Toxin

by Letizia Polito, Massimo Bortolotti, Maria Giulia Battelli, Giulia Calafato and Andrea Bolognesi

Toxins 2019, 11(6), 324; https://doi.org/10.3390/toxins11060324 - 6 Jun 2019

Cited by 110 | Viewed by 21745

Abstract

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, [...] Read more.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation. Full article

(This article belongs to the Special Issue Ricin Toxins)

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15 pages, 1237 KiB

Open AccessEditor’s ChoiceArticle

Prevalence and Genetic Diversity of Toxin Genes in Clinical Isolates of Clostridium perfringens: Coexistence of Alpha-Toxin Variant and Binary Enterotoxin Genes (bec/cpile)

by Asami Matsuda, Meiji Soe Aung, Noriko Urushibara, Mitsuyo Kawaguchiya, Ayako Sumi, Mayumi Nakamura, Yuka Horino, Masahiko Ito, Satoshi Habadera and Nobumichi Kobayashi

Toxins 2019, 11(6), 326; https://doi.org/10.3390/toxins11060326 - 6 Jun 2019

Cited by 22 | Viewed by 5155

Abstract

Clostridium perfringens (C. perfringens) is responsible for food-borne gastroenteritis and other infectious diseases, and toxins produced by this bacterium play a key role in pathogenesis. Although various toxins have been described for C. perfringens isolates from humans and animals, prevalence of [...] Read more.

Clostridium perfringens (C. perfringens) is responsible for food-borne gastroenteritis and other infectious diseases, and toxins produced by this bacterium play a key role in pathogenesis. Although various toxins have been described for C. perfringens isolates from humans and animals, prevalence of individual toxins among clinical isolates has not yet been well explored. In the present study, a total of 798 C. perfringens clinical isolates were investigated for prevalence of eight toxin genes and their genetic diversity by PCR, nucleotide sequencing, and phylogenetic analysis. Besides the alpha-toxin gene (plc) present in all the isolates, the most common toxin gene was cpe (enterotoxin) (34.2%), followed by cpb2 (beta2 toxin) (1.4%), netB (NetB) (0.3%), and bec/cpile (binary enterotoxin BEC/CPILE) (0.1%), while beta-, epsilon-, and iota-toxin genes were not detected. Genetic analysis of toxin genes indicated a high level of conservation of plc, cpe, and netB. In contrast, cpb2 was revealed to be considerably divergent, containing at least two lineages. Alpha-toxin among 46 isolates was classified into ten sequence types, among which common types were distinct from those reported for avian isolates. A single isolate with bec/cpile harbored a plc variant containing an insertion of 834-bp sequence, suggesting its putative origin from chickens. Full article

(This article belongs to the Collection Clostridium difficile/Clostridium sordellii and Clostridium perfringens Toxins)

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15 pages, 1198 KiB

Open AccessEditor’s ChoiceArticle

Deoxynivalenol-3-Glucoside Content Is Highly Associated with Deoxynivalenol Levels in Two-Row Barley Genotypes of Importance to Canadian Barley Breeding Programs

by James R. Tucker, Ana Badea, Richard Blagden, Kerri Pleskach, Sheryl A. Tittlemier and W. G. Dilantha Fernando

Toxins 2019, 11(6), 319; https://doi.org/10.3390/toxins11060319 - 5 Jun 2019

Cited by 27 | Viewed by 4776

Abstract

Barley (Hordeum vulgare L.) is a multipurpose crop that can be harvested as grain or cut prior to maturity for use as forage. Fusarium head blight (FHB) is a devastating disease of barley that reduces quality of grain. FHB can also result [...] Read more.

Barley (Hordeum vulgare L.) is a multipurpose crop that can be harvested as grain or cut prior to maturity for use as forage. Fusarium head blight (FHB) is a devastating disease of barley that reduces quality of grain. FHB can also result in the accumulation of mycotoxins such as deoxynivalenol (DON). Breeding FHB resistant varieties has been a long-term goal of many barley-producing countries, including Canada. While the genetic basis of DON detoxification via production of less-phytotoxic conjugates such as DON-3-glucoside (DON3G) is well documented in barley, little information exists in reference to varietal response. Over two years, 16 spring, two-row barley genotypes, of importance to western Canadian barley breeding programs, were grown as short-rows and inoculated following spike emergence with a Fusarium graminearum conidia suspension. Half of the plots were harvested at soft dough stage and then dissected into rachis and grain components, whereas the remainder was harvested at maturity. Multiple Fusarium-mycotoxins were assayed using liquid chromatography-mass spectrometry. Mycotoxin content was elevated at the earlier harvest point, especially in the rachis tissue. DON3G constituted a significant percentage (26%) of total trichothecene content and thus its co-occurrence with DON should be considered by barley industries. DON3G was highly correlated with DON and 3-acetyl-deoxynivalenol (3ADON). The ratio of D3G/DON exhibited consistency across genotypes, however more-resistant genotypes were characterized by a higher ratio at the soft-dough stage followed by a decrease at maturity. Plant breeding practices that use DON content as a biomarker for resistance would likely result in the development of barley cultivars with lower total DON-like compounds. Full article

(This article belongs to the Special Issue 2^nd MycoKey International Conference - Integrated Solutions for Mycotoxin Management)

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13 pages, 857 KiB

Open AccessEditor’s ChoiceReview

Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis

by Fabio Seiti Yamada Yoshikawa, Josenilson Feitosa de Lima, Maria Notomi Sato, Yasmin Álefe Leuzzi Ramos, Valeria Aoki and Raquel Leao Orfali

Toxins 2019, 11(6), 321; https://doi.org/10.3390/toxins11060321 - 5 Jun 2019

Cited by 48 | Viewed by 11848

Abstract

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its [...] Read more.

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense pruritus and xerosis. AD pathogenesis is multifactorial, involving genetic, environmental, and immunological factors, including the participation of Staphylococcus aureus. This bacterium colonizes up to 30–100% of AD skin and its virulence factors are responsible for its pathogenicity and antimicrobial survival. This is a concise review of S. aureus superantigen-activated signaling pathways, highlighting their involvement in AD pathogenesis, with an emphasis on skin barrier disruption, innate and adaptive immunity dysfunction, and microbiome alterations. A better understanding of the combined mechanisms of AD pathogenesis may enhance the development of future targeted therapies for this complex disease. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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15 pages, 1570 KiB

Open AccessEditor’s ChoiceArticle

Identification of the Fungal Pathogens of Postharvest Disease on Peach Fruits and the Control Mechanisms of Bacillus subtilis JK-14

by Shuwu Zhang, Qi Zheng, Bingliang Xu and Jia Liu

Toxins 2019, 11(6), 322; https://doi.org/10.3390/toxins11060322 - 5 Jun 2019

Cited by 71 | Viewed by 11287

Abstract

Postharvest fungal disease is one of the significant factors that limits the storage period and marketing life of peaches, and even result in serious economic losses worldwide. Biological control using microbial antagonists has been explored as an alternative approach for the management of [...] Read more.

Postharvest fungal disease is one of the significant factors that limits the storage period and marketing life of peaches, and even result in serious economic losses worldwide. Biological control using microbial antagonists has been explored as an alternative approach for the management of postharvest disease of fruits. However, there is little information available regarding to the identification the fungal pathogen species that cause the postharvest peach diseases and the potential and mechanisms of using the Bacillus subtilis JK-14 to control postharvest peach diseases. In the present study, a total of six fungal isolates were isolated from peach fruits, and the isolates of Alternaria tenuis and Botrytis cinerea exhibited the highest pathogenicity and virulence on the host of mature peaches. In the culture plates, the strain of B. subtilis JK-14 showed the significant antagonistic activity against the growth of A. tenuis and B. cinerea with the inhibitory rates of 81.32% and 83.45% at 5 days after incubation, respectively. Peach fruits treated with different formulations of B. subtilis JK-14 significantly reduced the mean disease incidences and lesion diameters of A. tenuis and B. cinerea. The greatest mean percent reduction of the disease incidences (81.99% and 71.34%) and lesion diameters (82.80% and 73.57%) of A. tenuis and B. cinerea were obtained at the concentration of 1 × 10⁷ CFU mL⁻¹ (colony forming unit, CFU). Treatment with the strain of B. subtilis JK-14 effectively enhanced the activity of the antioxidant enzymes-superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in A. tenuis and B. cinerea inoculated peach fruits. As such, the average activities of SOD, POD and CAT were increased by 36.56%, 17.63% and 20.35%, respectively, compared to the sterile water treatment. Our results indicate that the isolates of A. tenuis and B. cinerea are the main pathogens that cause the postharvest peach diseases, and the strain of B. subtilis JK-14 can be considered as an environmentally-safe biological control agent for the management of postharvest fruits diseases. We propose the possible mechanisms of the strain of B. subtilis JK-14 in controlling of postharvest peach diseases. Full article

(This article belongs to the Collection Understanding Mycotoxin Occurrence in Food and Feed Chains)

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12 pages, 2555 KiB

Open AccessEditor’s ChoiceArticle

A Gold Growth-Based Plasmonic ELISA for the Sensitive Detection of Fumonisin B₁ in Maize

by Shengnan Zhan, Lingyan Zheng, Yaofeng Zhou, Kesheng Wu, Hong Duan, Xiaolin Huang and Yonghua Xiong

Toxins 2019, 11(6), 323; https://doi.org/10.3390/toxins11060323 - 5 Jun 2019

Cited by 18 | Viewed by 4235

Abstract

In this paper, a highly sensitive plasmonic enzyme-linked immunosorbent assay (pELISA) was developed for the naked-eye detection of fumonisin B₁ (FB₁). Glucose oxidase (GOx) was used as an alternative to horseradish peroxidase as the carrier of the competing antigen. GOx [...] Read more.

In this paper, a highly sensitive plasmonic enzyme-linked immunosorbent assay (pELISA) was developed for the naked-eye detection of fumonisin B₁ (FB₁). Glucose oxidase (GOx) was used as an alternative to horseradish peroxidase as the carrier of the competing antigen. GOx catalyzed the oxidation of glucose to produce hydrogen peroxide, which acted as a reducing agent to reduce Au³⁺ to Au on the surface of gold seeds (5 nm), This reaction led to a color change in the solution from colorless to purple, which was observable to the naked eye. Various parameters that could influence the detection performance of pELISA were investigated. The developed method exhibited a considerably high sensitivity for FB₁ qualitative naked-eye detection, with a visible cut-off limit of 1.25 ng/mL. Moreover, the proposed pELISA showed a good linear range of 0.31–10 ng/mL with a half maximal inhibitory concentration (IC₅₀) of 1.86 ng/mL, which was approximately 13-fold lower than that of a horseradish peroxidase- (HRP)-based conventional ELISA. Meanwhile, the proposed method was highly specific and accurate. In summary, the new pELISA exhibited acceptable accuracy and precision for sensitive naked-eye detection of FB₁ in maize samples and can be applied for the detection of other chemical contaminants. Full article

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

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18 pages, 2861 KiB

Open AccessEditor’s ChoiceArticle

The Influence of Processing Parameters on the Mitigation of Deoxynivalenol during Industrial Baking

by David Stadler, Francesca Lambertini, Lydia Woelflingseder, Heidi Schwartz-Zimmermann, Doris Marko, Michele Suman, Franz Berthiller and Rudolf Krska

Toxins 2019, 11(6), 317; https://doi.org/10.3390/toxins11060317 - 4 Jun 2019

Cited by 33 | Viewed by 5113

Abstract

Deoxynivalenol (DON), a frequent contaminant of flour, can be partially degraded by baking. It is not clear: (i) How the choice of processing parameter (i.e., ingredients, leavening, and baking conditions) affects DON degradation and thus (ii) how much DON can be degraded during [...] Read more.

Deoxynivalenol (DON), a frequent contaminant of flour, can be partially degraded by baking. It is not clear: (i) How the choice of processing parameter (i.e., ingredients, leavening, and baking conditions) affects DON degradation and thus (ii) how much DON can be degraded during the large-scale industrial production of bakery products. Crackers, biscuits, and bread were produced from naturally contaminated flour using different processing conditions. DON degradation during baking was quantified with the most accurate analytical methodology available for this Fusarium toxin, which is based on liquid chromatography tandem mass spectrometry. Depending on the processing conditions, 0–21%, 4–16%, and 2–5% DON were degraded during the production of crackers, biscuits, and bread, respectively. A higher NaHCO₃ concentration, baking time, and baking temperature caused higher DON degradation. NH₄HCO₃, yeast, vinegar, and sucrose concentration as well as leavening time did not enhance DON degradation. In vitro cell viability assays confirmed that the major degradation product isoDON is considerably less toxic than DON. This proves for the first time that large-scale industrial baking results in partial detoxification of DON, which can be enhanced by process management. Full article

(This article belongs to the Special Issue Fate of Free, “Masked” and Conjugated/Modified forms of Mycotoxins)

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16 pages, 800 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin

by Leticia Díez-Quijada, Ana I. Prieto, María Puerto, Ángeles Jos and Ana M. Cameán

Toxins 2019, 11(6), 318; https://doi.org/10.3390/toxins11060318 - 4 Jun 2019

Cited by 16 | Viewed by 3639

Abstract

The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into [...] Read more.

The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk^± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins. Full article

(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)

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21 pages, 2529 KiB

Open AccessEditor’s ChoiceReview

Mitigating Aflatoxin Contamination in Groundnut through A Combination of Genetic Resistance and Post-Harvest Management Practices

by Manish K. Pandey, Rakesh Kumar, Arun K. Pandey, Pooja Soni, Sunil S. Gangurde, Hari K. Sudini, Jake C. Fountain, Boshou Liao, Haile Desmae, Patrick Okori, Xiaoping Chen, Huifang Jiang, Venugopal Mendu, Hamidou Falalou, Samuel Njoroge, James Mwololo, Baozhu Guo, Weijian Zhuang, Xingjun Wang, Xuanqiang Liang and Rajeev K. Varshney Show full author list Hide full author list

Toxins 2019, 11(6), 315; https://doi.org/10.3390/toxins11060315 - 3 Jun 2019

Cited by 88 | Viewed by 12453

Abstract

Aflatoxin is considered a “hidden poison” due to its slow and adverse effect on various biological pathways in humans, particularly among children, in whom it leads to delayed development, stunted growth, liver damage, and liver cancer. Unfortunately, the unpredictable behavior of the fungus [...] Read more.

Aflatoxin is considered a “hidden poison” due to its slow and adverse effect on various biological pathways in humans, particularly among children, in whom it leads to delayed development, stunted growth, liver damage, and liver cancer. Unfortunately, the unpredictable behavior of the fungus as well as climatic conditions pose serious challenges in precise phenotyping, genetic prediction and genetic improvement, leaving the complete onus of preventing aflatoxin contamination in crops on post-harvest management. Equipping popular crop varieties with genetic resistance to aflatoxin is key to effective lowering of infection in farmer’s fields. A combination of genetic resistance for in vitro seed colonization (IVSC), pre-harvest aflatoxin contamination (PAC) and aflatoxin production together with pre- and post-harvest management may provide a sustainable solution to aflatoxin contamination. In this context, modern “omics” approaches, including next-generation genomics technologies, can provide improved and decisive information and genetic solutions. Preventing contamination will not only drastically boost the consumption and trade of the crops and products across nations/regions, but more importantly, stave off deleterious health problems among consumers across the globe. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 3102 KiB

Open AccessEditor’s ChoiceArticle

Xanthium strumarium Fruit Extract Inhibits ATG4B and Diminishes the Proliferation and Metastatic Characteristics of Colorectal Cancer Cells

by Hsueh-Wei Chang, Pei-Feng Liu, Wei-Lun Tsai, Wan-Hsiang Hu, Yu-Chang Hu, Hsiu-Chen Yang, Wei-Yu Lin, Jing-Ru Weng and Chih-Wen Shu

Toxins 2019, 11(6), 313; https://doi.org/10.3390/toxins11060313 - 2 Jun 2019

Cited by 30 | Viewed by 5018

Abstract

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant [...] Read more.

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA₂. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells. Full article

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

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12 pages, 2734 KiB

Open AccessEditor’s ChoiceArticle

A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients

by Supitchaya Traisaeng, Deron Raymond Herr, Hsin-Jou Kao, Tsung-Hsien Chuang and Chun-Ming Huang

Toxins 2019, 11(6), 311; https://doi.org/10.3390/toxins11060311 - 31 May 2019

Cited by 54 | Viewed by 6701

Abstract

The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in [...] Read more.

The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in the production of butyric acid and effectively hindered the growth of a Staphylococcus aureus (S. aureus) strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD S. aureus. A derivative of butyric acid, BA–NH–NH–BA, was synthesized by conjugation of two butyric acids to both ends of an –NH–O–NH– linker. BA–NH–NH–BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD S. aureus. Like butyric acid, BA–NH–NH–BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA–NH–NH–BA ameliorated AD S. aureus-induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD S. aureus in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and S. aureus bactericidal activity. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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26 pages, 2193 KiB

Open AccessEditor’s ChoiceArticle

Mycotoxins at the Start of the Food Chain in Costa Rica: Analysis of Six Fusarium Toxins and Ochratoxin A between 2013 and 2017 in Animal Feed and Aflatoxin M₁ in Dairy Products

by Andrea Molina, Guadalupe Chavarría, Margarita Alfaro-Cascante, Astrid Leiva and Fabio Granados-Chinchilla

Toxins 2019, 11(6), 312; https://doi.org/10.3390/toxins11060312 - 31 May 2019

Cited by 18 | Viewed by 5355

Abstract

Mycotoxins are secondary metabolites, produced by fungi of genera Aspergillus, Penicillium and Fusarium (among others), which produce adverse health effects on humans and animals (carcinogenic, teratogenic and immunosuppressive). In addition, mycotoxins negatively affect the productive parameters of livestock (e.g., weight, food consumption, [...] Read more.

Mycotoxins are secondary metabolites, produced by fungi of genera Aspergillus, Penicillium and Fusarium (among others), which produce adverse health effects on humans and animals (carcinogenic, teratogenic and immunosuppressive). In addition, mycotoxins negatively affect the productive parameters of livestock (e.g., weight, food consumption, and food conversion). Epidemiological studies are considered necessary to assist stakeholders with the process of decision-making regarding the control of mycotoxins in processing environments. This study addressed the prevalence in feed ingredients and compound feed of eight different types of toxins, including metabolites produced by Fusarium spp. (Deoxynivalenol/3-acetyldeoxynivalenol, T-2/HT-2 toxins, zearalenone and fumonisins) and two additional toxins (i.e., ochratoxin A (OTA) and aflatoxin M₁ (AFM₁)) from different fungal species, for over a period of five years. On the subject of Fusarium toxins, higher prevalences were observed for fumonisins (n = 80/113, 70.8%) and DON (n = 212/363, 58.4%), whereas, for OTA, a prevalence of 40.56% was found (n = 146/360). In the case of raw material, mycotoxin contamination exceeding recommended values were observed in cornmeal for HT-2 toxin (n = 3/24, 12.5%), T-2 toxin (n = 3/61, 4.9%), and ZEA (n = 2/45, 4.4%). In contrast, many compound feed samples exceeded recommended values; in dairy cattle feed toxins such as DON (n = 5/147, 3.4%), ZEA (n = 6/150, 4.0%), T-2 toxin (n = 10/171, 5.9%), and HT-2 toxin (n = 13/132, 9.8%) were observed in high amounts. OTA was the most common compound accompanying Fusarium toxins (i.e., 16.67% of co-occurrence with ZEA). This study also provided epidemiological data for AFM₁ in liquid milk. The outcomes unveiled a high prevalence of contamination (i.e., 29.6–71.1%) and several samples exceeding the regulatory threshold. Statistical analysis exposed no significant climate effect connected to the prevalence of diverse types of mycotoxins. Full article

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

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9 pages, 281 KiB

Open AccessEditor’s ChoiceCommunication

Occurrence of Deoxynivalenol and Ochratoxin A in Beers and Wines Commercialized in Paraguay

by Andrea Alejandra Arrúa, Juliana Moura Mendes, Pablo Arrúa, Francisco Paulo Ferreira, Gabriela Caballero, Cinthia Cazal, Man Mohan Kohli, Inocencia Peralta, Gabriela Ulke and Danilo Fernández Ríos

Toxins 2019, 11(6), 308; https://doi.org/10.3390/toxins11060308 - 30 May 2019

Cited by 12 | Viewed by 5289

Abstract

Alcoholic beverages can be contaminated with mycotoxins. Ochratoxin A (OTA) is the most frequently detected mycotoxinin wine and is produced by several species of Aspergillus. This mycotoxin is nephrotoxic and carcinogenic. In beer, the most commonly identified mycotoxin is deoxynivalenol (DON). Ingestion of [...] Read more.

Alcoholic beverages can be contaminated with mycotoxins. Ochratoxin A (OTA) is the most frequently detected mycotoxinin wine and is produced by several species of Aspergillus. This mycotoxin is nephrotoxic and carcinogenic. In beer, the most commonly identified mycotoxin is deoxynivalenol (DON). Ingestion of food contaminated with DON has been associated with adverse gastrointestinal effects. Despite the harmful effects of mycotoxins on health, there are no regulations regarding their limits in alcoholic beverages in Paraguay. Here we determine the presence of OTA and DON in wine and beer, respectively. Four commercial brands of wine and twenty-nine brands of craft and industrial beerwere tested by the Agra quant ELISA method. One brand of wine was positive for OTA and seven brands of beer (one of them craft) were positive for DON. The values found for both toxins are below the recommended maximum intake proposed by international standards. Giving the high consumption of these products in the country, regulations and monitoring systems mustbe established to check the maximum levels of mycotoxins allowed in alcoholic beverages. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

23 pages, 336 KiB

Open AccessEditor’s ChoiceReview

Assorted Methods for Decontamination of Aflatoxin M1 in Milk Using Microbial Adsorbents

by Jean Claude Assaf, Sahar Nahle, Ali Chokr, Nicolas Louka, Ali Atoui and André El Khoury

Toxins 2019, 11(6), 304; https://doi.org/10.3390/toxins11060304 - 29 May 2019

Cited by 64 | Viewed by 6183

Abstract

Aflatoxins (AF) are carcinogenic metabolites produced by different species of Aspergillus which readily colonize crops. AFM1 is secreted in the milk of lactating mammals through the ingestion of feedstuffs contaminated by aflatoxin B1 (AFB1). Therefore, its presence in milk, even in small amounts, [...] Read more.

Aflatoxins (AF) are carcinogenic metabolites produced by different species of Aspergillus which readily colonize crops. AFM1 is secreted in the milk of lactating mammals through the ingestion of feedstuffs contaminated by aflatoxin B1 (AFB1). Therefore, its presence in milk, even in small amounts, presents a real concern for dairy industries and consumers of dairy products. Different strategies can lead to the reduction of AFM1 contamination levels in milk. They include adopting good agricultural practices, decreasing the AFB1 contamination of animal feeds, or using diverse types of adsorbent materials. One of the most effective types of adsorbents used for AFM1 decontamination are those of microbial origin. This review discusses current issues about AFM1 decontamination methods. These methods are based on the use of different bio-adsorbent agents such as bacteria and yeasts to complex AFM1 in milk. Moreover, this review answers some of the raised concerns about the binding stability of the formed AFM1-microbial complex. Thus, the efficiency of the decontamination methods was addressed, and plausible experimental variants were discussed. Full article

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

9 pages, 581 KiB

Open AccessEditor’s ChoiceArticle

Genotypes, Enterotoxin Gene Profiles, and Antimicrobial Resistance of Staphylococcus aureus Associated with Foodborne Outbreaks in Hangzhou, China

by Qi Chen and Sangma Xie

Toxins 2019, 11(6), 307; https://doi.org/10.3390/toxins11060307 - 29 May 2019

Cited by 38 | Viewed by 4422

Abstract

Staphylococcal food poisoning is an illness caused by the consumption of food that contains sufficient amounts of one or more enterotoxins. In the present study, a total of 37 S. aureus isolates were recovered from leftover food, swabs from a kitchen environment, and [...] Read more.

Staphylococcal food poisoning is an illness caused by the consumption of food that contains sufficient amounts of one or more enterotoxins. In the present study, a total of 37 S. aureus isolates were recovered from leftover food, swabs from a kitchen environment, and patient feces associated with four foodborne outbreaks that occurred in Hangzhou, southeast China, and were characterized by multilocus sequence typing (MLST), spa typing, pulse-field gel electrophoresis (PFGE), and antimicrobial susceptibility. Classical enterotoxin and enterotoxin-like genes were profiled by PCR analysis. ST6-t304 was the most common clone (40.54%), followed by ST2315-t11687 (32.43%). Six clusters (A to F) were divided based on PFGE patterns, and Clusters A and C were the most common types, constituting 86.49% of all isolates. Moreover, sea was the most frequently identified enterotoxin gene (81.08%), followed by the combination of seg–sei–selm–seln–sleo–selu and sec–sell (each 48.65%). Five isolates also harbored the exotoxin cluster sed–selj–ser. In addition, resistance to penicillin (97.30%), erythromycin (37.85), tetracycline (32.43%), clindamycin, gentamicin, and sulfamethoxazole (each 10.81%) was observed. Our research demonstrated the link between leftover foods and patients by molecular typing and detecting the profiles of enterotoxin or enterotoxin-like genes in human and food isolates. S. aureus maintains an extensive repertoire of enterotoxins and drug resistance genes that could cause potential health threats to consumers. Full article

(This article belongs to the Collection Bacterial Enterotoxins)

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22 pages, 3551 KiB

Open AccessEditor’s ChoiceArticle

Degrading Ochratoxin A and Zearalenone Mycotoxins Using a Multifunctional Recombinant Enzyme

by Md Shofiul Azam, Dianzhen Yu, Na Liu and Aibo Wu

Toxins 2019, 11(5), 301; https://doi.org/10.3390/toxins11050301 - 27 May 2019

Cited by 71 | Viewed by 7556

Abstract

Zearalenone (ZEA) is an estrogenic and ochratoxin A (OTA) is a hepatotoxic Fusarium mycotoxin commonly seen in cereals and fruits products. No previous investigation has studied on a single platform for the multi degradation mycotoxin. The current study aimed to investigate the bifunctional [...] Read more.

Zearalenone (ZEA) is an estrogenic and ochratoxin A (OTA) is a hepatotoxic Fusarium mycotoxin commonly seen in cereals and fruits products. No previous investigation has studied on a single platform for the multi degradation mycotoxin. The current study aimed to investigate the bifunctional activity of a novel fusion recombinant. We have generated a recombinant fusion enzyme (ZHDCP) by combining two single genes named zearalenone hydrolase (ZHD) and carboxypeptidase (CP) in frame deletion by crossover polymerase chain reaction (PCR). We identified enzymatic properties and cell cytotoxicity assay of ZHDCP enzyme. Our findings have demonstrated that ZEA was completely degraded to the non-toxic product in 2 h by ZHDCP enzyme at an optimum pH of 7 and a temperature of 35 °C. For the first time, it was found out that ZEA 60% was degraded by CP degrades in 48 h. Fusion ZHDCP and CP enzyme were able to degrade 100% OTA in 30 min at pH 7 and temperature 30 °C. ZEA- and OTA-induced cell death and increased cell apoptosis rate and regulated mRNA expression of Sirt1, Bax, Bcl2, Caspase3, TNFα, and IL6 genes. Our novel findings demonstrated that the fusion enzyme ZHDCP possess bifunctional activity (degrade OTA and ZEA), and it could be used to degrade more mycotoxins. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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26 pages, 4727 KiB

Open AccessEditor’s ChoiceReview

Tremorgenic Mycotoxins: Structure Diversity and Biological Activity

by Priyanka Reddy, Kathryn Guthridge, Simone Vassiliadis, Joanne Hemsworth, Inoka Hettiarachchige, German Spangenberg and Simone Rochfort

Toxins 2019, 11(5), 302; https://doi.org/10.3390/toxins11050302 - 27 May 2019

Cited by 59 | Viewed by 6986

Abstract

Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to Epichloë species, whilst penitrem production is confined to Penicillium spp. and Aspergillus spp. These fungal species are often present [...] Read more.

Indole-diterpenes are an important class of chemical compounds which can be unique to different fungal species. The highly complex lolitrem compounds are confined to Epichloë species, whilst penitrem production is confined to Penicillium spp. and Aspergillus spp. These fungal species are often present in association with pasture grasses, and the indole-diterpenes produced may cause toxicity in grazing animals. In this review, we highlight the unique structural variations of indole-diterpenes that are characterised into subgroups, including paspaline, paxilline, shearinines, paspalitrems, terpendoles, penitrems, lolitrems, janthitrems, and sulpinines. A detailed description of the unique biological activities has been documented where even structurally related compounds have displayed unique biological activities. Indole-diterpene production has been reported in two classes of ascomycete fungi, namely Eurotiomycetes (e.g., Aspergillus and Penicillium) and Sordariomycetes (e.g., Claviceps and Epichloë). These compounds all have a common structural core comprised of a cyclic diterpene skeleton derived from geranylgeranyl diphosphate (GGPP) and an indole moiety derived from tryptophan. Structure diversity is generated from the enzymatic conversion of different sites on the basic indole-diterpene structure. This review highlights the wide-ranging biological versatility presented by the indole-diterpene group of compounds and their role in an agricultural and pharmaceutical setting. Full article

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

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15 pages, 1385 KiB

Open AccessEditor’s ChoiceReview

From Snake Venom’s Disintegrins and C-Type Lectins to Anti-Platelet Drugs

by Philip Lazarovici, Cezary Marcinkiewicz and Peter I. Lelkes

Toxins 2019, 11(5), 303; https://doi.org/10.3390/toxins11050303 - 27 May 2019

Cited by 45 | Viewed by 9802

Abstract

Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin [...] Read more.

Snake venoms are attractive natural sources for drug discovery and development, with a number of substances either in clinical use or in research and development. These drugs were developed based on RGD-containing snake venom disintegrins, which efficiently antagonize fibrinogen activation of αIIbβ3 integrin (glycoprotein GP IIb/IIIa). Typical examples of anti-platelet drugs found in clinics are Integrilin (Eptifibatide), a heptapeptide derived from Barbourin, a protein found in the venom of the American Southeastern pygmy rattlesnake and Aggrastat (Tirofiban), a small molecule based on the structure of Echistatin, and a protein found in the venom of the saw-scaled viper. Using a similar drug discovery approach, linear and cyclic peptides containing the sequence K(R)TS derived from VP12, a C-type lectin protein found in the venom of Israeli viper venom, were used as a template to synthesize Vipegitide, a novel peptidomimetic antagonist of α2β1 integrin, with anti-platelet activity. This review focus on drug discovery of these anti-platelet agents, their indications for clinical use in acute coronary syndromes and percutaneous coronary intervention based on several clinical trials, as well as their adverse effects. Full article

(This article belongs to the Special Issue From Toxins to Drugs)

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16 pages, 898 KiB

Open AccessEditor’s ChoiceArticle

Effects of Predator-Prey Interactions on Predator Traits: Differentiation of Diets and Venoms of a Marine Snail

by David A. Weese and Thomas F. Duda, Jr.

Toxins 2019, 11(5), 299; https://doi.org/10.3390/toxins11050299 - 25 May 2019

Cited by 11 | Viewed by 5024

Abstract

Species interactions are fundamental ecological forces that can have significant impacts on the evolutionary trajectories of species. Nonetheless, the contribution of predator-prey interactions to genetic and phenotypic divergence remains largely unknown. Predatory marine snails of the family Conidae exhibit specializations for different prey [...] Read more.

Species interactions are fundamental ecological forces that can have significant impacts on the evolutionary trajectories of species. Nonetheless, the contribution of predator-prey interactions to genetic and phenotypic divergence remains largely unknown. Predatory marine snails of the family Conidae exhibit specializations for different prey items and intraspecific variation in prey utilization patterns at geographic scales. Because cone snails utilize venom to capture prey and venom peptides are direct gene products, it is feasible to examine the evolution of genes associated with changes in resource utilization. Here, we compared feeding ecologies and venom duct transcriptomes of individuals from three populations of Conus miliaris, a species that exhibits geographic variation in prey utilization and dietary breadth, in order to determine the extent to which dietary differences are correlated with differences in venom composition, and if expanded niche breadth is associated with increased variation in venom composition. While populations showed little to no overlap in resource utilization, taxonomic richness of prey was greatest at Easter Island. Changes in dietary breadth were associated with differences in expression patterns and increased genetic differentiation of toxin-related genes. The Easter Island population also exhibited greater diversity of toxin-related transcripts, but did not show increased variance in expression of these transcripts. These results imply that differences in dietary breadth contribute more to the structural and regulatory differentiation of venoms than differences in diet. Full article

(This article belongs to the Special Issue Diversity and Pharmacological Discovery from Venoms of Conus and other Conidaeans)

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14 pages, 2241 KiB

Open AccessEditor’s ChoiceArticle

Evidence for Snake Venom Plasticity in a Long-Term Study with Individual Captive Bothrops atrox

by Diana R. Amazonas, Luciana A. Freitas-de-Sousa, Daniele P. Orefice, Leijiane F. de Sousa, Melissa G. Martinez, Rosa H. V. Mourão, Hipócrates M. Chalkidis, Plínio B. Camargo and Ana M. Moura-da-Silva

Toxins 2019, 11(5), 294; https://doi.org/10.3390/toxins11050294 - 24 May 2019

Cited by 22 | Viewed by 4776

Abstract

Variability in snake venom composition has been frequently reported and correlated to the adaptability of snakes to environmental conditions. Previous studies report plasticity for the venom phenotype. However, these observations are not conclusive, as the results were based on pooled venoms, which present [...] Read more.

Variability in snake venom composition has been frequently reported and correlated to the adaptability of snakes to environmental conditions. Previous studies report plasticity for the venom phenotype. However, these observations are not conclusive, as the results were based on pooled venoms, which present high individual variability. Here we tested the hypothesis of plasticity by influence of confinement and single diet type in the venom composition of 13 adult specimens of Bothrops atrox snakes, maintained under captivity for more than three years. Individual variability in venom composition was observed in samples extracted just after the capture of the snakes. However, composition was conserved in venoms periodically extracted from nine specimens, which presented low variability restricted to the less abundant components. In a second group, composed of four snakes, drastic changes were observed in the venom samples extracted at different periods, mostly related to snake venom metalloproteinases (SVMPs), the core function toxins of B. atrox venom, which occurred approximately between 400 and 500 days in captivity. These data show plasticity in the venom phenotype during the lifetime of adult snakes maintained under captive conditions. Causes or functional consequences involved in the phenotype modification require further investigations. Full article

(This article belongs to the Section Animal Venoms)

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11 pages, 1860 KiB

Open AccessEditor’s ChoiceArticle

Fengycin Produced by Bacillus amyloliquefaciens FZB42 Inhibits Fusarium graminearum Growth and Mycotoxins Biosynthesis

by Alvina Hanif, Feng Zhang, Pingping Li, Chuchu Li, Yujiao Xu, Muhammad Zubair, Mengxuan Zhang, Dandan Jia, Xiaozhen Zhao, Jingang Liang, Taha Majid, Jingyuau Yan, Ayaz Farzand, Huijun Wu, Qin Gu and Xuewen Gao

Toxins 2019, 11(5), 295; https://doi.org/10.3390/toxins11050295 - 24 May 2019

Cited by 111 | Viewed by 7817

Abstract

Fusarium graminearum is a notorious pathogen that causes Fusarium head blight (FHB) in cereal crops. It produces secondary metabolites, such as deoxynivalenol, diminishing grain quality and leading to lesser crop yield. Many strategies have been developed to combat this pathogenic fungus; however, considering [...] Read more.

Fusarium graminearum is a notorious pathogen that causes Fusarium head blight (FHB) in cereal crops. It produces secondary metabolites, such as deoxynivalenol, diminishing grain quality and leading to lesser crop yield. Many strategies have been developed to combat this pathogenic fungus; however, considering the lack of resistant cultivars and likelihood of environmental hazards upon using chemical pesticides, efforts have shifted toward the biocontrol of plant diseases, which is a sustainable and eco-friendly approach. Fengycin, derived from Bacillus amyloliquefaciens FZB42, was purified from the crude extract by HPLC and further analyzed by MALDI-TOF-MS. Its application resulted in structural deformations in fungal hyphae, as observed via scanning electron microscopy. In planta experiment revealed the ability of fengycin to suppress F. graminearum growth and highlighted its capacity to combat disease incidence. Fengycin significantly suppressed F. graminearum, and also reduced the deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and zearalenone (ZEN) production in infected grains. To conclude, we report that fengycin produced by B. amyloliquefaciens FZB42 has potential as a biocontrol agent against F. graminearum and can also inhibit the mycotoxins produced by this fungus. Full article

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

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25 pages, 3888 KiB

Open AccessEditor’s ChoiceArticle

Time-Dependent Changes in the Intestinal Microbiome of Gilts Exposed to Low Zearalenone Doses

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

Toxins 2019, 11(5), 296; https://doi.org/10.3390/toxins11050296 - 24 May 2019

Cited by 26 | Viewed by 3741

Abstract

Zearalenone is a frequent contaminant of cereals and their by-products in regions with a temperate climate. This toxic molecule is produced naturally by Fusarium fungi in crops. The aim of this study was to determine the influence of low zearalenone doses (LOAEL, NOAEL [...] Read more.

Zearalenone is a frequent contaminant of cereals and their by-products in regions with a temperate climate. This toxic molecule is produced naturally by Fusarium fungi in crops. The aim of this study was to determine the influence of low zearalenone doses (LOAEL, NOAEL and MABEL) on the intestinal microbiome of gilts on different days of exposure (days 7, 21 and 42). Intestinal contents were sampled from the duodenal cap, the third part of the duodenum, jejunum, caecum and the descending colon. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg /kg BW, group ZEN10—10 μg ZEN/kg BW and group ZEN15—15 µg ZEN/kg BW. Five gilts from every group were euthanized on analytical dates 1, 2 and 3. Differences in the log values of microbial counts, mainly Escherichia coli and Enterococcus faecalis, were observed between the proximal and distal segments of the intestinal tract on different analytical dates as well as in the entire intestinal tract. Zearalenone affected the colony counts of intestinal microbiota rather than microbiome diversity, and its effect was greatest in groups ZEN10 and ZEN15. Microbial colony counts were similar in groups ZEN5 and C. In the analysed mycobiome, ZEN exerted a stimulatory effect on the log values of yeast and mould counts in all intestinal segments, in particular in the colon, and the greatest increase was noted on the first analytical date. Full article

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

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15 pages, 2323 KiB

Open AccessEditor’s ChoiceArticle

Bacterial Lipopolysaccharide Induced Alterations of Genome-Wide DNA Methylation and Promoter Methylation of Lactation-Related Genes in Bovine Mammary Epithelial Cells

by Jingbo Chen, Yongjiang Wu, Yawang Sun, Xianwen Dong, Zili Wang, Zhu Zhang, Yanli Xiao and Guozhong Dong

Toxins 2019, 11(5), 298; https://doi.org/10.3390/toxins11050298 - 24 May 2019

Cited by 33 | Viewed by 3986

Abstract

Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this [...] Read more.

Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this study was to investigate the impact of LPS on genome-wide DNA methylation, using methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) and on the promoter methylation of lactation-related genes using MassArray analysis in bovine mammary epithelial cells. The bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng). The results showed that the genomic methylation levels and the number of methylated genes in the genome as well as the promoter methylation levels of milk genes increased when the LPS dose was raised from 0 to 10 EU/mL, but decreased after further increasing the LPS dose. The milk gene mRNA expression levels of the 10 EU/mL LPS treatment were significantly lower than these of untreated cells. The results also showed that the number of hypermethylated genes was greater than that of hypomethylated genes in lipid and amino acid metabolic pathways following 1 and 10 EU/mL LPS treatments as compared with control. By contrast, in the immune response pathway the number of hypomethylated genes increased with increasing LPS doses. The results indicate LPS at lower doses induced hypermethylation of the genome and promoters of lactation-related genes, affecting milk gene mRNA expression. However, LPS at higher doses induced hypomethylation of genes involved in the immune response pathway probably in favor of immune responses. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)

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11 pages, 1262 KiB

Open AccessEditor’s ChoiceCommunication

Study on the Growth and Enterotoxin Production by Staphylococcus aureus in Canned Meat before Retorting

by Luca Grispoldi, Paul Alexanderu Popescu, Musafiri Karama, Vito Gullo, Giusi Poerio, Elena Borgogni, Paolo Torlai, Giuseppina Chianese, Anna Giovanna Fermani, Paola Sechi and Beniamino Cenci-Goga

Toxins 2019, 11(5), 291; https://doi.org/10.3390/toxins11050291 - 23 May 2019

Cited by 27 | Viewed by 6629

Abstract

Possible contamination by Staphylococcus aureus of the production environment and of the meat of a canned meat production factory was analysed. A total of 108 samples were taken from nine critical control points, 13 of them were positive for S. aureus. [...] Read more.

Possible contamination by Staphylococcus aureus of the production environment and of the meat of a canned meat production factory was analysed. A total of 108 samples were taken from nine critical control points, 13 of them were positive for S. aureus. None of the isolates produced enterotoxins. To determine how much time can elapse between can seaming and sterilisation in the autoclave without any risk of enterotoxin production by S. aureus, the growth and enterotoxin production of three enterotoxin A producing strains of S. aureus (one ATCC strain and two field strains) in canned meat before sterilisation was investigated at three different temperatures (37, 20 and 10 °C). Two types of meat were used, one with and one without sodium nitrite. In the canned products, the spiked bacteria spread throughout the meat and reached high levels. Enterotoxin production was shown to start 10 hours after incubation at 37 °C and after 48 h after incubation at 20 °C; the production of enterotoxin was always detected in the transition between the exponential and the stationary growth phase. At 10 °C, the enterotoxin was never detected. The statistical analysis of the data showed that the difference between the two different types of meat was not statistically significant (p value > 0.05). Since it is well known that following heat treatment, staphylococcal enterotoxins, although still active (in in vivo assays), can be undetectable (loss of serological recognition) depending on the food matrix and pH, it is quite difficult to foresee the impact of heat treatment on enterotoxin activity. Therefore, although the bacteria are eliminated, the toxins may remain and cause food poisoning. The significance of the results of this study towards implementing good manufacturing practices and hazard analysis critical control points in a canned meat factory are discussed with reference to the management of pre-retorting steps after seaming. Full article

(This article belongs to the Special Issue Staphylococcus aureus Toxins)

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15 pages, 3048 KiB

Open AccessEditor’s ChoiceArticle

Discovery of a Potential Human Serum Biomarker for Chronic Seafood Toxin Exposure Using an SPR Biosensor

by Kathi A. Lefebvre, Betsy Jean Yakes, Elizabeth Frame, Preston Kendrick, Sara Shum, Nina Isoherranen, Bridget E. Ferriss, Alison Robertson, Alicia Hendrix, David J. Marcinek and Lynn Grattan

Toxins 2019, 11(5), 293; https://doi.org/10.3390/toxins11050293 - 23 May 2019

Cited by 12 | Viewed by 5208

Abstract

Domoic acid (DA)-producing harmful algal blooms (HABs) have been present at unprecedented geographic extent and duration in recent years causing an increase in contamination of seafood by this common environmental neurotoxin. The toxin is responsible for the neurotoxic illness, amnesic shellfish poisoning (ASP), [...] Read more.

Domoic acid (DA)-producing harmful algal blooms (HABs) have been present at unprecedented geographic extent and duration in recent years causing an increase in contamination of seafood by this common environmental neurotoxin. The toxin is responsible for the neurotoxic illness, amnesic shellfish poisoning (ASP), that is characterized by gastro-intestinal distress, seizures, memory loss, and death. Established seafood safety regulatory limits of 20 μg DA/g shellfish have been relatively successful at protecting human seafood consumers from short-term high-level exposures and episodes of acute ASP. Significant concerns, however, remain regarding the potential impact of repetitive low-level or chronic DA exposure for which there are no protections. Here, we report the novel discovery of a DA-specific antibody in the serum of chronically-exposed tribal shellfish harvesters from a region where DA is commonly detected at low levels in razor clams year-round. The toxin was also detected in tribal shellfish consumers’ urine samples confirming systemic DA exposure via consumption of legally-harvested razor clams. The presence of a DA-specific antibody in the serum of human shellfish consumers confirms long-term chronic DA exposure and may be useful as a diagnostic biomarker in a clinical setting. Adverse effects of chronic low-level DA exposure have been previously documented in laboratory animal studies and tribal razor clam consumers, underscoring the potential clinical impact of such a diagnostic biomarker for protecting human health. The discovery of this type of antibody response to chronic DA exposure has broader implications for other environmental neurotoxins of concern. Full article

(This article belongs to the Special Issue Marine Biotoxins and Seafood Poisoning)

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62 pages, 487 KiB

Open AccessEditor’s ChoiceReview

Prevalent Mycotoxins in Animal Feed: Occurrence and Analytical Methods

by Carolina Santos Pereira, Sara C. Cunha and José O. Fernandes

Toxins 2019, 11(5), 290; https://doi.org/10.3390/toxins11050290 - 22 May 2019

Cited by 178 | Viewed by 14127

Abstract

Today, we have been witnessing a steady tendency in the increase of global demand for maize, wheat, soybeans, and their products due to the steady growth and strengthening of the livestock industry. Thus, animal feed safety has gradually become more important, with mycotoxins [...] Read more.

Today, we have been witnessing a steady tendency in the increase of global demand for maize, wheat, soybeans, and their products due to the steady growth and strengthening of the livestock industry. Thus, animal feed safety has gradually become more important, with mycotoxins representing one of the most significant hazards. Mycotoxins comprise different classes of secondary metabolites of molds. With regard to animal feed, aflatoxins, fumonisins, ochratoxins, trichothecenes, and zearalenone are the more prevalent ones. In this review, several constraints posed by these contaminants at economical and commercial levels will be discussed, along with the legislation established in the European Union to restrict mycotoxins levels in animal feed. In addition, the occurrence of legislated mycotoxins in raw materials and their by-products for the feeds of interest, as well as in the feeds, will be reviewed. Finally, an overview of the different sample pretreatment and detection techniques reported for mycotoxin analysis will be presented, the main weaknesses of current methods will be highlighted. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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13 pages, 275 KiB

Open AccessEditor’s ChoiceArticle

Yellow Mealworm Larvae (Tenebrio molitor) Fed Mycotoxin-Contaminated Wheat—A Possible Safe, Sustainable Protein Source for Animal Feed?

by Carlos Ochoa Sanabria, Natacha Hogan, Kayla Madder, Cedric Gillott, Barry Blakley, Martin Reaney, Aaron Beattie and Fiona Buchanan

Toxins 2019, 11(5), 282; https://doi.org/10.3390/toxins11050282 - 21 May 2019

Cited by 29 | Viewed by 5899

Abstract

The aim of this study was to determine the potential for accumulation of deoxynivalenol (DON) in yellow mealworm larvae (Tenebrio molitor) reared on high DON Fusarium-infected wheat and investigate the effects on production, survival and nutritional traits. Wheat containing 200 [...] Read more.

The aim of this study was to determine the potential for accumulation of deoxynivalenol (DON) in yellow mealworm larvae (Tenebrio molitor) reared on high DON Fusarium-infected wheat and investigate the effects on production, survival and nutritional traits. Wheat containing 200 μg/kg DON was used as the control diet. A different source of wheat was sorted into six fractions and mixed to obtain low (2000 μg/kg), medium (10,000 μg/kg) and high (12,000 μg/kg) levels of DON. Each diet was replicated five times with 300 or 200 mealworms per replicate for the feeding and breeding trials, respectively. Trial termination occurred when the first two pupae were observed (32–34 days). There was no difference in the concentrations of DON detected in the larvae between diets that ranged from 122 ± 19.3 to 136 ± 40.5 μg/kg (p = 0.88). Excretion of DON was 131, 324, 230 and 742 μg/kg for control, low, medium and high, respectively. Nutritional analysis of larvae showed maximum crude protein of 52% and crude fat of 36%. Ash, fiber, chitin, fatty-acids and amino-acid content were consistent across diets. Survival was greater than 96% for all life stages and average daily gain ranged from 1.9 ± 0.1 to 2.1 ± 0.1 mg/day per mealworm. Larvae accumulated low levels of DON from Fusarium-infected wheat diets suggesting contaminated wheat could be used to produce a sustainable, safe protein source. Full article

(This article belongs to the Special Issue Dietary Mycotoxin Exposure to Livestock and Poultry)

11 pages, 1476 KiB

Open AccessEditor’s ChoiceArticle

Development of an Anti-Idiotypic VHH Antibody and Toxin-Free Enzyme Immunoassay for Ochratoxin A in Cereals

by Caixia Zhang, Qi Zhang, Xiaoqian Tang, Wen Zhang and Peiwu Li

Toxins 2019, 11(5), 280; https://doi.org/10.3390/toxins11050280 - 20 May 2019

Cited by 27 | Viewed by 4207

Abstract

Enzyme-linked immunosorbent assay (ELISA) test kits have been widely used for the determination of mycotoxins in agricultural products and foods, however, this test uses toxin standards with high toxicity and carcinogenicity that seriously threaten human health. In this work, the anti-idiotypic nanobody VHH [...] Read more.

Enzyme-linked immunosorbent assay (ELISA) test kits have been widely used for the determination of mycotoxins in agricultural products and foods, however, this test uses toxin standards with high toxicity and carcinogenicity that seriously threaten human health. In this work, the anti-idiotypic nanobody VHH 2-24 was first developed and then, using it as a surrogate standard, a toxin-free enzyme immunoassay for ochratoxin A (OTA) was established. The IC₅₀ value of the VHH 2-24 surrogate standard-based ELISA was 0.097 µg/mL, with a linear range of 0.027–0.653 µg/mL. The average recoveries were tested by spike-and-recovery experiments, and ranged from 81.8% to 105.0%. The accuracy of the developed ELISA for detecting OTA was further verified by using the high performance liquid chromatography (HPLC) method, and an excellent correlation was observed. In summary, the toxin-free ELISA established in this study proves the latent use of the anti-idiotypic VHH as a surrogate calibrator for other mycotoxins and highly toxic small molecule analysis to improve assay properties for highly sensitive analyte determination in agricultural products. Full article

(This article belongs to the Special Issue Fungal Infestations in Humans, Animals, Crops)

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16 pages, 3084 KiB

Open AccessEditor’s ChoiceArticle

Binding to The Target Cell Surface Is The Crucial Step in Pore Formation of Hemolysin BL from Bacillus cereus

by Nadja Jessberger, Richard Dietrich, Stefanie Schwemmer, Franziska Tausch, Valerie Schwenk, Andrea Didier and Erwin Märtlbauer

Toxins 2019, 11(5), 281; https://doi.org/10.3390/toxins11050281 - 20 May 2019

Cited by 27 | Viewed by 4127

Abstract

A major virulence factor involved in Bacillus cereus food poisoning is the three-component enterotoxin hemolysin BL. It consists of the binding component B and the two lytic components L₁ and L₂. Studying its mode of action has been challenging, as [...] Read more.

A major virulence factor involved in Bacillus cereus food poisoning is the three-component enterotoxin hemolysin BL. It consists of the binding component B and the two lytic components L₁ and L₂. Studying its mode of action has been challenging, as natural culture supernatants additionally contain Nhe, the second three-component enterotoxin, and purification of recombinant (r) Hbl components has been difficult. In this study, we report on pore-forming, cytotoxic, cell binding and hemolytic activity of recently generated rHbl components expressed in E. coli. It is known that all three Hbl components are necessary for cytotoxicity and pore formation. Here we show that an excess of rHbl B enhances, while an excess of rHbl L₁ hinders, the velocity of pore formation. Most rapid pore formation was observed with ratios L₂:L₁:B = 1:1:10 and 10:1:10. It was further verified that Hbl activity is due to sequential binding of the components B - L₁ - L₂. Accordingly, all bioassays proved that binding of Hbl B to the cell surface is the crucial step for pore formation and cytotoxic activity. Binding of Hbl B took place within minutes, while apposition of the following L₁ and L₂ occurred immediately. Further on, applying toxin components simultaneously, it seemed that Hbl L₁ enhanced binding of B to the target cell surface. Overall, these data contribute significantly to the elucidation of the mode of action of Hbl, and suggest that its mechanism of pore formation differs substantially from that of Nhe, although both enterotoxin complexes are sequentially highly related. Full article

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

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17 pages, 2457 KiB

Open AccessEditor’s ChoiceArticle

Impact of Five Succinate Dehydrogenase Inhibitors on DON Biosynthesis of Fusarium asiaticum, Causing Fusarium Head Blight in Wheat

by Chao Xu, Meixia Li, Zehua Zhou, Jiaosheng Li, Dongming Chen, Yabing Duan and Mingguo Zhou

Toxins 2019, 11(5), 272; https://doi.org/10.3390/toxins11050272 - 15 May 2019

Cited by 42 | Viewed by 5457

Abstract

Deoxynivalenol (DON) is a class of mycotoxin produced in cereal crops infected with Fusarium graminearum species complex (FGSC). In China, FGSC mainly includes Fusarium asiaticum and F. graminearum. DON belongs to the trichothecenes and poses a serious threat to the safety and [...] Read more.

Deoxynivalenol (DON) is a class of mycotoxin produced in cereal crops infected with Fusarium graminearum species complex (FGSC). In China, FGSC mainly includes Fusarium asiaticum and F. graminearum. DON belongs to the trichothecenes and poses a serious threat to the safety and health of humans and animals. Succinate dehydrogenase inhibitors (SDHIs) are a class of fungicides that act on succinate dehydrogenase and inhibit the respiration of pathogenic fungi. In this study, the fungicidal activities of five SDHIs, including fluopyram, flutolanil, boscalid, benzovindiflupyr, and fluxapyroxad, against FGSC were determined based on mycelial growth and spore germination inhibition methods. The five SDHIs exhibited better inhibitory activities in spore germination than mycelial growth. Fluopyram exhibited a higher inhibitory effect in mycelial growth and spore germination in comparison to the other four SDHIs. In addition, the biological characteristics of F. asiaticum as affected by the five SDHIs were determined. We found that these five SDHIs decreased DON, pyruvic acid and acetyl-CoA production, isocitrate dehydrogenase mitochondrial (ICDHm) and SDH activities, and NADH and ATP content of F. asiaticum but increased the citric acid content. In addition, TRI5 gene expression was inhibited, and the formation of toxisomes was disrupted by the five SDHIs, further confirming that SDHIs can decrease DON biosynthesis of F. asiaticum. Thus, we concluded that SDHIs may decrease DON biosynthesis of F. asiaticum by inhibiting glycolysis and the tricarboxylic acid (TCA) cycle. Overall, the findings from the study will provide important references for managing Fusarium head blight (FHB) caused by FGSC and reducing DON contamination in F. asiaticum-infected wheat grains. Full article

(This article belongs to the Special Issue Recent Advances in Fusarium Research)

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14 pages, 10288 KiB

Open AccessEditor’s ChoiceArticle

Label-Free Direct Detection of Saxitoxin Based on a Localized Surface Plasmon Resonance Aptasensor

by Su-Ji Ha, Jin-Ho Park, Bobin Lee and Min-Gon Kim

Toxins 2019, 11(5), 274; https://doi.org/10.3390/toxins11050274 - 15 May 2019

Cited by 42 | Viewed by 5856

Abstract

Seafood is an emerging health food, and interest in improving the quality of seafood is increasing. Saxitoxin (STX) is a neurotoxin produced by marine dinoflagellates that is accumulated in seafood. It can block the neuronal transmission between nerves and muscle cell membranes, resulting [...] Read more.

Seafood is an emerging health food, and interest in improving the quality of seafood is increasing. Saxitoxin (STX) is a neurotoxin produced by marine dinoflagellates that is accumulated in seafood. It can block the neuronal transmission between nerves and muscle cell membranes, resulting in the disturbance of neuromuscular transmission and subsequent voluntary muscle paralysis. Here, we developed a new aptamer for the detection of STX using graphene oxide–systematic evolution of ligands by exponential enrichment (GO-SELEX). Furthermore, we confirmed sensitivity and selectivity of the developed aptamer specific to STX using a localized surface plasmon resonance (LSPR) sensor. The sensing chip was fabricated by fixing the new STX aptamer immobilized on the gold nanorod (GNR) substrate. The STX LSPR aptasensor showed a broad, linear detection range from 5 to 10,000 μg/L, with a limit of detection (LOD) of 2.46 μg/L (3σ). Moreover, it was suitable for the detection of STX (10, 100, and 2000 μg/L) in spiked mussel samples and showed a good recovery rate (96.13–116.05%). The results demonstrated that the new STX aptamer-modified GNR chip was sufficiently sensitive and selective to detect STX and can be applied to real samples as well. This LSPR aptasensor is a simple, label-free, cost-effective sensing system with a wide detectable range. Full article

(This article belongs to the Special Issue Emerging Nanotechnology in Toxins Research)

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19 pages, 3513 KiB

Open AccessEditor’s ChoiceReview

Cannabis: From a Plant That Modulates Feeding Behaviors toward Developing Selective Inhibitors of the Peripheral Endocannabinoid System for the Treatment of Obesity and Metabolic Syndrome

by Shira Hirsch and Joseph Tam

Toxins 2019, 11(5), 275; https://doi.org/10.3390/toxins11050275 - 15 May 2019

Cited by 28 | Viewed by 7207

Abstract

In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB₁R), are commonly known as mediators of the thrifty phenotype hypothesis due to their activity in [...] Read more.

In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB₁R), are commonly known as mediators of the thrifty phenotype hypothesis due to their activity in the central nervous system, which in turn regulates food intake and underlies the development of metabolic syndrome. Indeed, these findings led to the clinical testing of globally acting CB₁R blockers for obesity and various metabolic complications. However, their therapeutic potential was halted due to centrally mediated adverse effects. Recent observations that highlighted the key role of the peripheral eCB system in metabolic regulation led to the preclinical development of various novel compounds that block CB₁R only in peripheral organs with very limited brain penetration and without causing behavioral side effects. These unique molecules, which effectively ameliorate obesity, type II diabetes, fatty liver, insulin resistance, and chronic kidney disease in several animal models, are likely to be further developed in the clinic and may revive the therapeutic potential of blocking CB₁R once again. Full article

(This article belongs to the Special Issue From Toxins to Drugs)

15 pages, 1508 KiB

Open AccessEditor’s ChoiceArticle

Assessment of Aflatoxin and Fumonisin Contamination and Associated Risk Factors in Feed and Feed Ingredients in Rwanda

by Kizito Nishimwe, Erin Bowers, Jean de Dieu Ayabagabo, Richard Habimana, Samuel Mutiga and Dirk Maier

Toxins 2019, 11(5), 270; https://doi.org/10.3390/toxins11050270 - 14 May 2019

Cited by 41 | Viewed by 6564

Abstract

Mycotoxins are fungal metabolites that contaminate crops, food, and animal feeds. Aflatoxins and fumonisins are among the mycotoxins that have been increasingly reported to affect health and productivity of livestock globally. Given that the health and productivity of livestock can directly influence human [...] Read more.

Mycotoxins are fungal metabolites that contaminate crops, food, and animal feeds. Aflatoxins and fumonisins are among the mycotoxins that have been increasingly reported to affect health and productivity of livestock globally. Given that the health and productivity of livestock can directly influence human food safety and security, a study was conducted to assess the levels and factors for aflatoxin and fumonisin contamination in feed and feed ingredients in Rwanda. Aflatoxins and fumonisins were analyzed in 3328 feed and feed ingredient samples collected at six time points between March and October 2017 in all 30 districts of Rwanda. Of the 612 participants providing samples, there were 10 feed processors, 68 feed vendors, 225 dairy farmers, and 309 poultry farmers. Enzyme-Linked Immunosorbent Assay (ELISA) was used for aflatoxin and fumonisin analyses. Mean aflatoxin levels of 108.83 µg/kg (Median (MD): 43.65 µg/kg), 103.81µg/kg (MD: 48.4 µg/kg), 88.64 µg/kg (MD: 30.90 µg/kg), and 94.95 µg/kg (MD: 70.45 µg/kg) were determined for dairy farmers, poultry farmers, feed vendors, and feed processors, respectively. Mean fumonisin levels were 1.52 mg/kg (MD: 0.71 mg/kg), 1.21 mg/kg (MD: 0.56 mg/kg), 1.48 mg/kg (MD: 0.76 mg/kg), and 1.03 mg/kg (MD: 0.47 mg/kg) for dairy farmers, poultry farmers, feed vendors, and feed processors, respectively. Aflatoxin contamination was significantly affected by time of sampling and district from which feed samples originated (p < 0.05). Fumonisins did not show any correlation trends. Ninety-two percent of survey participants were unaware of aflatoxins and fumonisins and their adverse effects. This study has provided the basic understanding of the extent of feed contamination across the country and has established a baseline for future interventions in Rwanda. Further studies are needed to explore strategies for mitigating mycotoxins in the feed value chain in Rwanda. Full article

(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)

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20 pages, 7039 KiB

Open AccessEditor’s ChoiceArticle

Long Term Monitoring (2014–2018) of Multi-Mycotoxins in South African Commercial Maize and Wheat with a Locally Developed and Validated LC-MS/MS Method

by Hannalien Meyer, Zanele Diana Skhosana, Mamsy Motlanthe, Wiana Louw and Egmont Rohwer

Toxins 2019, 11(5), 271; https://doi.org/10.3390/toxins11050271 - 14 May 2019

Cited by 22 | Viewed by 4569

Abstract

Mycotoxins occur worldwide in the major grains, and producers, traders and processors are all challenged to prevent serious health problems for consumers. The challenges originate with pre-harvest fungi infections in the grain fields, increased contamination during improper storage and, finally, the mycotoxin accumulation [...] Read more.

Mycotoxins occur worldwide in the major grains, and producers, traders and processors are all challenged to prevent serious health problems for consumers. The challenges originate with pre-harvest fungi infections in the grain fields, increased contamination during improper storage and, finally, the mycotoxin accumulation in commercial food and feed products. Little is known about the multi-mycotoxin occurrence in maize and wheat commercially produced in South Africa. This is the first comprehensive study that reports on the multi-mycotoxin occurrence in South African produced maize and wheat crops after harvest, over four production seasons, in all the production regions of the country. The study was made possible with the development of a fit-for-purpose, cost-effective LC-MS/MS multi-mycotoxin method, validated for 13 “regulated” mycotoxins. A low mycotoxin risk was found in South African produced wheat, with only deoxynivalenol (DON) in 12.5% of the 160 samples at levels well below the 2000 µg/kg South African (SA) regulatory level. It was concluded that aflatoxin B₁ (AFB₁) is seldom present in South African produced commercial maize. The concentrations, regional variation and seasonal trends of deoxynivalenol and fumonisins, the two most prevalent mycotoxins, and of zearalenone (ZON), are reported for white and yellow maize in all the production provinces, based on the analytical results of 1400 maize samples. A threefold to eightfold increase in deoxynivalenol mean concentrations in white maize was observed in the main production regions in the fourth season, with 8.9% samples above 2000 µg/kg. A strong correlation was found between higher deoxynivalenol concentrations and the presence of 15-acetyl-deoxynivalenol (15-ADON). The mean fumonisin concentrations were well below the 4000 µg/kg South African regulatory value. A possible shift in the incidence and severity of mycotoxigenic Fusarium spp. in the provinces must be investigated. The variations and trends highlight the importance of a continuous monitoring of multi-mycotoxins in South Africa along the grain value chain. Full article

(This article belongs to the Special Issue Fungal Growth and Mycotoxins: Challenges for developing countries)

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16 pages, 5225 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets

by Giane Favretto, Regiane Stafim da Cunha, Maria Aparecida Dalboni, Rodrigo Bueno de Oliveira, Fellype de Carvalho Barreto, Ziad A. Massy and Andréa Emilia Marques Stinghen

Toxins 2019, 11(5), 267; https://doi.org/10.3390/toxins11050267 - 13 May 2019

Cited by 23 | Viewed by 5481

Abstract

Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic [...] Read more.

Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established. Full article

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

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12 pages, 2797 KiB

Open AccessEditor’s ChoiceArticle

Isolation of a Novel Microcystin-Degrading Bacterium and the Evolutionary Origin of mlr Gene Cluster

by Lian Qin, Xiaoxing Zhang, Xiaoguo Chen, Ke Wang, Yitian Shen and Dan Li

Toxins 2019, 11(5), 269; https://doi.org/10.3390/toxins11050269 - 13 May 2019

Cited by 18 | Viewed by 4064

Abstract

The mlr-dependent biodegradation plays an essential role in the natural attenuation of microcystins (MCs) in eutrophic freshwater ecosystems. However, their evolutionary origin is still unclear due to the lack of mlr gene cluster sequences. In this study, a Sphingopyxis sp. strain X20 [...] Read more.

The mlr-dependent biodegradation plays an essential role in the natural attenuation of microcystins (MCs) in eutrophic freshwater ecosystems. However, their evolutionary origin is still unclear due to the lack of mlr gene cluster sequences. In this study, a Sphingopyxis sp. strain X20 with high MC-degrading ability was isolated, and the mlrA gene activity was verified by heterologous expression. The whole sequence of the mlr gene cluster in strain X20 was obtained through PCR and thermal asymmetric interlaced (TAIL)-PCR, and then used for evolutionary origin analyses together with the sequences available in GenBank. Phylogenetic analyses of mlr gene clusters suggested that the four mlr genes had the same origin and evolutionary history. Genomic island analyses showed that there is a genomic island on the genome of sphingomonads that is capable of degrading MCs, on which the mlr gene cluster anchors. The concentrated distribution of the mlr gene cluster in sphingomonads implied that these genes have likely been present in the sphingomonads gene pool for a considerable time. Therefore, the mlr gene cluster may have initially entered into the genome of sphingomonads together with the genomic island by a horizontal gene transfer event, and then become inherited by some sphingomonads. The species other than sphingomonads have likely acquired mlr genes from sphingomonads by recently horizontal gene transfer due to the sporadic distribution of MC-degrading species and the mlr genes in them. Our results shed new light on the evolutionary origin of the mlr cluster and thus facilitate the interpretation of characteristic distribution of the mlr gene in bacteria and the understanding of whole mlr pathway. Full article

(This article belongs to the Collection Toxicological Challenges of Aquatic Toxins)

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