Toxins

15 pages, 782 KiB

Open AccessEditor’s ChoiceArticle

Use of Mustard Extracts Fermented by Lactic Acid Bacteria to Mitigate the Production of Fumonisin B₁ and B₂ by Fusarium verticillioides in Corn Ears

by Raquel Torrijos, Tiago de Melo Nazareth, Pilar Vila-Donat, Jordi Mañes and Giuseppe Meca

Toxins 2022, 14(2), 80; https://doi.org/10.3390/toxins14020080 - 21 Jan 2022

Cited by 4 | Viewed by 4337

Abstract

Corn (Zea mays) is a worldwide crop subjected to infection by toxigenic fungi such as Fusarium verticillioides during the pre-harvest stage. Fusarium contamination can lead to the synthesis of highly toxic mycotoxins, such as Fumonisin B₁ (FB₁) and [...] Read more.

Corn (Zea mays) is a worldwide crop subjected to infection by toxigenic fungi such as Fusarium verticillioides during the pre-harvest stage. Fusarium contamination can lead to the synthesis of highly toxic mycotoxins, such as Fumonisin B₁ (FB₁) and Fumonisin B₂ (FB₂), which compromises human and animal health. The work aimed to study the antifungal properties of fermented yellow and oriental mustard extracts using nine lactic acid bacteria (LAB) in vitro. Moreover, a chemical characterization of the main phenolic compounds and organic acids were carried out in the extracts. The results highlighted that the yellow mustard, fermented by Lactiplantibacillus plantarum strains, avoided the growth of Fusarium spp. in vitro, showing Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values, ranging from 7.8 to 15.6 g/L and 15.6 to 31.3 g/L, respectively. Then, the lyophilized yellow mustard fermented extract by L. plantarum TR71 was applied through spray-on corn ears contaminated with F. verticillioides to study the antimycotoxigenic activity. After 14 days of incubation, the control contained 14.71 mg/kg of FB₁, while the treatment reduced the content to 1.09 mg/kg (92.6% reduction). Moreover, no FB₂ was observed in the treated samples. The chemical characterization showed that lactic acid, 3-phenyllactic acid, and benzoic acid were the antifungal metabolites quantified in higher concentrations in the yellow mustard fermented extract with L. plantarum TR71. The results obtained confirmed the potential application of fermented mustard extracts as a solution to reduce the incidence of mycotoxins in corn ears. Full article

(This article belongs to the Special Issue Reduction and Control of Mycotoxins along Entire Food and Feed Chain)

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29 pages, 2616 KiB

Open AccessEditor’s ChoiceReview

Bioprospecting Phenols as Inhibitors of Trichothecene-Producing Fusarium: Sustainable Approaches to the Management of Wheat Pathogens

by Wiem Chtioui, Virgilio Balmas, Giovanna Delogu, Quirico Migheli and Safa Oufensou

Toxins 2022, 14(2), 72; https://doi.org/10.3390/toxins14020072 - 20 Jan 2022

Cited by 24 | Viewed by 6703

Abstract

Fusarium spp. are ubiquitous fungi able to cause Fusarium head blight and Fusarium foot and root rot on wheat. Among relevant pathogenic species, Fusarium graminearum and Fusarium culmorum cause significant yield and quality loss and result in contamination of the grain with mycotoxins, [...] Read more.

Fusarium spp. are ubiquitous fungi able to cause Fusarium head blight and Fusarium foot and root rot on wheat. Among relevant pathogenic species, Fusarium graminearum and Fusarium culmorum cause significant yield and quality loss and result in contamination of the grain with mycotoxins, mainly type B trichothecenes, which are a major health concern for humans and animals. Phenolic compounds of natural origin are being increasingly explored as fungicides on those pathogens. This review summarizes recent research activities related to the antifungal and anti-mycotoxigenic activity of natural phenolic compounds against Fusarium, including studies into the mechanisms of action of major exogenous phenolic inhibitors, their structure-activity interaction, and the combined effect of these compounds with other natural products or with conventional fungicides in mycotoxin modulation. The role of high-throughput analysis tools to decipher key signaling molecules able to modulate the production of mycotoxins and the development of sustainable formulations enhancing potential inhibitors’ efficacy are also discussed. Full article

(This article belongs to the Special Issue Fusarium and Fusarium Toxins)

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6 pages, 241 KiB

Open AccessEditor’s ChoiceArticle

Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection

by Joerg Mueller, Thomas Langbein, Aditi Mishra and Richard P. Baum

Toxins 2022, 14(1), 64; https://doi.org/10.3390/toxins14010064 - 17 Jan 2022

Cited by 15 | Viewed by 5157

Abstract

Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) [...] Read more.

Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) metastases but inevitably destroys SG due to unintended gland uptake. A preliminary case series with regular-dose IncoA failed to reduce SG PSMA-radioligand uptake. We therefore increased IncoA dosage in combination with transdermal scopolamine until a clinically relevant SG PSMA-radioligand uptake reduction was achieved. Ten consecutive men with metastasized PCa refractory to all other cancer therapies received gradually increasing IncoA dosages as part of a compassionate use PSMA-radioligand-therapy trial. The parotid gland received six and the submandibular gland three injection points under ultrasound control, up to a maximum of 30 units IncoA per injection point. A maximum total dose of 250 units IncoA was applied with up to 170 units per parotid and 80 units per submandibular gland. Treatment was well tolerated and all side-effects were non-serious. The most frequent side-effect was dry mouth of mild severity. No dysphagia, facial weakness, chewing difficulties or systemic side-effects were observed. SG injections with IncoA up to a total dose of 250 units are safe when distributed among several injection-points under ultrasound control by an experienced physician. These preliminary findings lay the basis for future trials including BTX as major component for SG protection in established as well as newly emerging radioligand cancer therapies. Full article

(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)

11 pages, 1888 KiB

Open AccessEditor’s ChoiceArticle

Discrimination of the Activity of Low-Affinity Wild-Type and High-Affinity Mutant Recombinant BoNT/B by a SIMA Cell-Based Reporter Release Assay

by Frank Neuschäfer-Rube, Andrea Pathe-Neuschäfer-Rube and Gerhard P. Püschel

Toxins 2022, 14(1), 65; https://doi.org/10.3390/toxins14010065 - 17 Jan 2022

Cited by 3 | Viewed by 3967

Abstract

Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences [...] Read more.

Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data. Full article

(This article belongs to the Section Bacterial Toxins)

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7 pages, 810 KiB

Open AccessEditor’s ChoiceReview

Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type

by Tino Vollmer and Bernd Stegmayr

Toxins 2022, 14(1), 54; https://doi.org/10.3390/toxins14010054 - 12 Jan 2022

Viewed by 3289

Abstract

The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with [...] Read more.

The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products. Full article

(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)

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16 pages, 3865 KiB

Open AccessEditor’s ChoiceArticle

Taqman qPCR Quantification and Fusarium Community Analysis to Evaluate Toxigenic Fungi in Cereals

by Elina Sohlberg, Vertti Virkajärvi, Päivi Parikka, Sari Rämö, Arja Laitila and Tuija Sarlin

Toxins 2022, 14(1), 45; https://doi.org/10.3390/toxins14010045 - 6 Jan 2022

Cited by 12 | Viewed by 3984

Abstract

Fusarium head blight (FHB) is an economically important plant disease. Some Fusarium species produce mycotoxins that cause food safety concerns for both humans and animals. One especially important mycotoxin-producing fungus causing FHB is Fusarium graminearum. However, Fusarium species form a disease complex [...] Read more.

Fusarium head blight (FHB) is an economically important plant disease. Some Fusarium species produce mycotoxins that cause food safety concerns for both humans and animals. One especially important mycotoxin-producing fungus causing FHB is Fusarium graminearum. However, Fusarium species form a disease complex where different Fusarium species co-occur in the infected cereals. Effective management strategies for FHB are needed. Development of the management tools requires information about the diversity and abundance of the whole Fusarium community. Molecular quantification assays for detecting individual Fusarium species and subgroups exist, but a method for the detection and quantification of the whole Fusarium group is still lacking. In this study, a new TaqMan-based qPCR method (FusE) targeting the Fusarium-specific elongation factor region (EF1α) was developed for the detection and quantification of Fusarium spp. The FusE method was proven as a sensitive method with a detection limit of 1 pg of Fusarium DNA. Fusarium abundance results from oat samples correlated significantly with deoxynivalenol (DON) toxin content. In addition, the whole Fusarium community in Finnish oat samples was characterized with a new metabarcoding method. A shift from F. culmorum to F. graminearum in FHB-infected oats has been detected in Europe, and the results of this study confirm that. These new molecular methods can be applied in the assessment of the Fusarium community and mycotoxin risk in cereals. Knowledge gained from the Fusarium community analyses can be applied in developing and selecting effective management strategies for FHB. Full article

(This article belongs to the Special Issue Selected Papers from the 15th European Fusarium Seminar)

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14 pages, 2101 KiB

Open AccessEditor’s ChoiceReview

A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain

by Anupam Datta Gupta, Suzanne Edwards, Jessica Smith, John Snow, Renuka Visvanathan, Graeme Tucker and David Wilson

Toxins 2022, 14(1), 36; https://doi.org/10.3390/toxins14010036 - 3 Jan 2022

Cited by 25 | Viewed by 6583

Abstract

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep [...] Read more.

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent. Full article

(This article belongs to the Section Bacterial Toxins)

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11 pages, 2864 KiB

Open AccessEditor’s ChoiceArticle

Trial Assay for Safe First-Aid Protocol for the Stinging Sea Anemone Anemonia viridis (Cnidaria: Anthozoa) and a Severe Toxic Reaction

by Ainara Ballesteros, Janire Salazar, Macarena Marambio, José Tena, José Rafael García-March, Diana López, Clara Tellez, Carles Trullas, Eric Jourdan, Corinne Granger and Josep-Maria Gili

Toxins 2022, 14(1), 27; https://doi.org/10.3390/toxins14010027 - 1 Jan 2022

Cited by 4 | Viewed by 5608

Abstract

Anemonia viridis is an abundant and widely distributed temperate sea anemone that can form dense congregations of individuals. Despite the potential severity of its sting, few detailed cases have been reported. We report a case of a severe toxic reaction following an A. [...] Read more.

Anemonia viridis is an abundant and widely distributed temperate sea anemone that can form dense congregations of individuals. Despite the potential severity of its sting, few detailed cases have been reported. We report a case of a severe toxic reaction following an A. viridis sting in a 35-year-old oceanographer. She developed severe pain, itching, redness, and burning sensation, which worsened one week after treatment with anti-inflammatories, antihistamines and corticosteroids. Prompted by this event, and due to the insufficient risk prevention, lack of training for marine-environment users, and lack of research into sting-specific first-aid protocols, we evaluated the cnidocyst response to five different compounds commonly recommended as rinse solutions in first-aid protocols (seawater, vinegar, ammonia, baking soda, and freshwater) by means of the Tentacle Solution Assay. Vinegar and ammonia triggered an immediate and massive cnidocyst discharge after their application and were classified as activator solutions. Baking soda and freshwater were also classified as activator solutions, although with a lower intensity of discharge. Only seawater was classified as a neutral solution and therefore recommended as a rinse solution after A. viridis sting, at least until an inhibitory solution is discovered. Full article

(This article belongs to the Special Issue Cnidarian Venom)

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18 pages, 2450 KiB

Open AccessEditor’s ChoiceArticle

Mycotoxin Interactions along the Gastrointestinal Tract: In Vitro Semi-Dynamic Digestion and Static Colonic Fermentation of a Contaminated Meal

by Maria Madalena Costa Sobral, Tiago Gonçalves, Zita E. Martins, Christine Bäuerl, Erika Cortés-Macías, Maria Carmen Collado and Isabel M. P. L. V. O. Ferreira

Toxins 2022, 14(1), 28; https://doi.org/10.3390/toxins14010028 - 1 Jan 2022

Cited by 13 | Viewed by 4407

Abstract

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) naturally co-occur in several foods, but no studies have followed the fate of mycotoxins’ interactions along the gastrointestinal tract using in vitro digestion models. This study used a novel semi-dynamic model that mimics gradual acidification and [...] Read more.

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) naturally co-occur in several foods, but no studies have followed the fate of mycotoxins’ interactions along the gastrointestinal tract using in vitro digestion models. This study used a novel semi-dynamic model that mimics gradual acidification and gastric emptying, coupled with a static colonic fermentation phase, in order to monitor mycotoxins’ bioaccessibility by the oral route. AFB1 and OTA bioaccessibility patterns differed in single or co-exposed scenarios. When co-exposed (MIX meal), AFB1 bioaccessibility at the intestinal level increased by ~16%, while OTA bioaccessibility decreased by ~20%. Additionally, a significant increase was observed in both intestinal cell viability and NO production. With regard to mycotoxin–probiotic interactions, the MIX meal showed a null effect on Lactobacillus and Bifidobacterium strain growth, while isolated AFB1 reduced bacterial growth parameters. These results were confirmed at phylum and family levels using a gut microbiota approach. After colonic fermentation, the fecal supernatant did not trigger the NF-kB activation pathway, indicating reduced toxicity of mycotoxins. In conclusion, if single exposed, AFB1 will have a significant impact on intestinal viability and probiotic growth, while OTA will mostly trigger NO production; in a co-exposure situation, both intestinal viability and inflammation will be affected, but the impact on probiotic growth will be neglected. Full article

(This article belongs to the Special Issue Mycotoxin Contamination and Food Safety)

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11 pages, 1310 KiB

Open AccessEditor’s ChoiceArticle

Influence of Prolonged Serotonin and Ergovaline Pre-Exposure on Vasoconstriction Ex Vivo

by Eriton E. L. Valente, David L. Harmon and James L. Klotz

Toxins 2022, 14(1), 9; https://doi.org/10.3390/toxins14010009 - 23 Dec 2021

Cited by 6 | Viewed by 3020

Abstract

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate [...] Read more.

Ergot alkaloid mycotoxins interfere in many functions associated with serotonergic neurotransmitters. Therefore, the objective was to evaluate whether the association of serotonin (5-hydroxytryptamine, 5-HT) and ergot alkaloids during a 24 h pre-incubation could affect the vascular contractile response to ergot alkaloids. To evaluate the effects of 24 h exposure to 5-HT and ergot alkaloids (ergovaline, ERV), two assays were conducted. The first assay determined the half-maximal inhibitory concentration (IC₅₀) following the 24 h pre-exposure period, while the second assay evaluated the effect of IC₅₀ concentrations of 5-HT and ERV either individually or in combination. There was an interaction between previous exposure to 5-HT and ERV. Previous exposure to 5-HT at the IC₅₀ concentration of 7.57 × 10⁻⁷ M reduced the contractile response by more than 50% of control, while the exposure to ERV at IC₅₀ dose of 1.57 × 10⁻¹⁰ M tended to decrease (p = 0.081) vessel contractility with a response higher than 50% of control. The 24 h previous exposure to both 5-HT and ERV did not potentiate the inhibitory response of blood vessels in comparison with incubation with each compound alone. These results suggest receptor competition between 5-HT and ERV. More studies are necessary to determine the potential of 5-HT to treat toxicosis caused by ergot alkaloids. Full article

(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)

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13 pages, 3718 KiB

Open AccessEditor’s ChoiceArticle

Structural Analysis of Botulinum Neurotoxins Type B and E by Cryo-EM

by Sara Košenina, Markel Martínez-Carranza, Jonathan R. Davies, Geoffrey Masuyer and Pål Stenmark

Toxins 2022, 14(1), 14; https://doi.org/10.3390/toxins14010014 - 23 Dec 2021

Cited by 8 | Viewed by 5035

Abstract

Botulinum neurotoxins (BoNTs) are the causative agents of a potentially lethal paralytic disease targeting cholinergic nerve terminals. Multiple BoNT serotypes exist, with types A, B and E being the main cause of human botulism. Their extreme toxicity has been exploited for cosmetic and [...] Read more.

Botulinum neurotoxins (BoNTs) are the causative agents of a potentially lethal paralytic disease targeting cholinergic nerve terminals. Multiple BoNT serotypes exist, with types A, B and E being the main cause of human botulism. Their extreme toxicity has been exploited for cosmetic and therapeutic uses to treat a wide range of neuromuscular disorders. Although naturally occurring BoNT types share a common end effect, their activity varies significantly based on the neuronal cell-surface receptors and intracellular SNARE substrates they target. These properties are the result of structural variations that have traditionally been studied using biophysical methods such as X-ray crystallography. Here, we determined the first structures of botulinum neurotoxins using single-particle cryogenic electron microscopy. The maps obtained at 3.6 and 3.7 Å for BoNT/B and /E, respectively, highlight the subtle structural dynamism between domains, and of the binding domain in particular. This study demonstrates how the recent advances made in the field of single-particle electron microscopy can be applied to bacterial toxins of clinical relevance and the botulinum neurotoxin family in particular. Full article

(This article belongs to the Special Issue Structure and Function of Clostridial and Botulinum-Like Neurotoxins)

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13 pages, 929 KiB

Open AccessEditor’s ChoiceArticle

Collagen-Derived Peptides in CKD: A Link to Fibrosis

by Emmanouil Mavrogeorgis, Harald Mischak, Agnieszka Latosinska, Antonia Vlahou, Joost P. Schanstra, Justyna Siwy, Vera Jankowski, Joachim Beige and Joachim Jankowski

Toxins 2022, 14(1), 10; https://doi.org/10.3390/toxins14010010 - 23 Dec 2021

Cited by 22 | Viewed by 11633

Abstract

Collagen is a major component of the extracellular matrix (ECM) and has an imminent role in fibrosis, in, among others, chronic kidney disease (CKD). Collagen alpha-1(I) (col1a1) is the most abundant collagen type and has previously been underlined for its contribution to the [...] Read more.

Collagen is a major component of the extracellular matrix (ECM) and has an imminent role in fibrosis, in, among others, chronic kidney disease (CKD). Collagen alpha-1(I) (col1a1) is the most abundant collagen type and has previously been underlined for its contribution to the disease phenotype. Here, we examined 5000 urinary peptidomic datasets randomly selected from healthy participants or patients with CKD to identify urinary col1a1 fragments and study their abundance, position in the main protein, as well as their correlation with renal function. We identified 707 col1a1 peptides that differed in their amino acid sequence and/or post-translational modifications (hydroxyprolines). Well-correlated peptides with the same amino acid sequence, but a different number of hydroxyprolines, were combined into a final list of 503 peptides. These 503 col1a1 peptides covered 69% of the full col1a1 sequence. Sixty-three col1a1 peptides were significantly and highly positively associated (rho > +0.3) with the estimated glomerular filtration rate (eGFR), while only six peptides showed a significant and strong, negative association (rho < −0.3). A similar tendency was observed for col1a1 peptides associated with ageing, where the abundance of most col1a1 peptides decreased with increasing age. Collectively the results show a strong association between collagen peptides and loss of kidney function and suggest that fibrosis, potentially also of other organs, may be the main consequence of an attenuation of collagen degradation, and not increased synthesis. Full article

(This article belongs to the Special Issue Kidney Disease-Gut Dysbiosis: What Is the Role of Uremic Toxins?)

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13 pages, 1910 KiB

Open AccessEditor’s ChoiceArticle

Indoxyl Sulfate Contributes to mTORC1-Induced Renal Fibrosis via The OAT/NADPH Oxidase/ROS Pathway

by Takehiro Nakano, Hiroshi Watanabe, Tadashi Imafuku, Kai Tokumaru, Issei Fujita, Nanaka Arimura, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa and Toru Maruyama

Toxins 2021, 13(12), 909; https://doi.org/10.3390/toxins13120909 - 18 Dec 2021

Cited by 34 | Viewed by 4908

Abstract

Activation of mTORC1 (mechanistic target of rapamycin complex 1) in renal tissue has been reported in chronic kidney disease (CKD)-induced renal fibrosis. However, the molecular mechanisms responsible for activating mTORC1 in CKD pathology are not well understood. The purpose of this study was [...] Read more.

Activation of mTORC1 (mechanistic target of rapamycin complex 1) in renal tissue has been reported in chronic kidney disease (CKD)-induced renal fibrosis. However, the molecular mechanisms responsible for activating mTORC1 in CKD pathology are not well understood. The purpose of this study was to identify the uremic toxin involved in mTORC1-induced renal fibrosis. Among the seven protein-bound uremic toxins, only indoxyl sulfate (IS) caused significant activation of mTORC1 in human kidney 2 cells (HK-2 cells). This IS-induced mTORC1 activation was inhibited in the presence of an organic anion transporter inhibitor, a NADPH oxidase inhibitor, and an antioxidant. IS also induced epithelial–mesenchymal transition of tubular epithelial cells (HK-2 cells), differentiation of fibroblasts into myofibroblasts (NRK-49F cells), and inflammatory response of macrophages (THP-1 cells), which are associated with renal fibrosis, and these effects were inhibited in the presence of rapamycin (mTORC1 inhibitor). In in vivo experiments, IS overload was found to activate mTORC1 in the mouse kidney. The administration of AST-120 or rapamycin targeted to IS or mTORC1 ameliorated renal fibrosis in Adenine-induced CKD mice. The findings reported herein indicate that IS activates mTORC1, which then contributes to renal fibrosis. Therapeutic interventions targeting IS and mTORC1 could be effective against renal fibrosis in CKD. Full article

(This article belongs to the Special Issue Contribution of Uremic Toxins to Chronic Kidney Disease Progression)

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14 pages, 5418 KiB

Open AccessEditor’s ChoiceArticle

Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for Clostridium perfringens Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells

by Basma Tarek, Julia Bruggisser, Filippo Cattalani and Horst Posthaus

Toxins 2021, 13(12), 893; https://doi.org/10.3390/toxins13120893 - 13 Dec 2021

Cited by 9 | Viewed by 5943

Abstract

Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by Clostridium perfringens type C. It plays a central role in the pathogenesis of necro-hemorrhagic enteritis in young animals and humans via targeting intestinal endothelial cells. We recently identified the membrane [...] Read more.

Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by Clostridium perfringens type C. It plays a central role in the pathogenesis of necro-hemorrhagic enteritis in young animals and humans via targeting intestinal endothelial cells. We recently identified the membrane protein CD31 (PECAM-1) as the receptor for CPB on mouse endothelial cells. We now assess the role of CD31 in CPB cytotoxicity against human endothelial and monocytic cells using a CRISPR/Cas9 gene knockout and an antibody blocking approach. CD31 knockout human endothelial and monocytic cells were resistant to CPB and CPB oligomers only formed in CD31-expressing cells. CD31 knockout endothelial and monocytic cells could be selectively enriched out of a polyclonal cell population by exposing them to CPB. Moreover, antibody mediated blocking of the extracellular Ig6 domain of CD31 abolished CPB cytotoxicity and oligomer formation in endothelial and monocytic cells. In conclusion, this study confirms the role of CD31 as a receptor of CPB on human endothelial and monocytic cells. Specific interaction with the CD31 molecule can thus explain the cell type specificity of CPB observed in vitro and corresponds to in vivo observations in naturally diseased animals. Full article

(This article belongs to the Special Issue Bacterial Exotoxins and Their Impact on Host–Pathogen Interaction in Animals and Humans)

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20 pages, 2039 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Analysis and Biological Characterization of Venom Components from Solitary Scoliid Wasp Campsomeriella annulata annulata

by Carlos Alberto-Silva, Fernanda Calheta Vieira Portaro, Roberto Tadashi Kodama, Halyne Queiroz Pantaleão, Hidetoshi Inagaki, Ken-ichi Nihei and Katsuhiro Konno

Toxins 2021, 13(12), 885; https://doi.org/10.3390/toxins13120885 - 10 Dec 2021

Cited by 8 | Viewed by 3120

Abstract

Venoms of solitary wasps are utilized for prey capture (insects and spiders), paralyzing them with a stinger injection to be offered as food for their larvae. Thus, the identification and characterization of the components of solitary wasp venoms can have biotechnological application. In [...] Read more.

Venoms of solitary wasps are utilized for prey capture (insects and spiders), paralyzing them with a stinger injection to be offered as food for their larvae. Thus, the identification and characterization of the components of solitary wasp venoms can have biotechnological application. In the present study, the venom components profile of a solitary scoliid wasp, Campsomeriella annulata annulata, was investigated through a comprehensive analysis using LC-MS and -MS/MS. Online mass fingerprinting revealed that the venom extract contains 138 components, and MS/MS analysis identified 44 complete sequences of the peptide components. The peptides are broadly divided into two classes: bradykinin-related peptides, and linear α-helical peptides. Among the components of the first class, the two main peptides, α-campsomerin (PRLRRLTGLSPLR) and β-campsomerin (PRLRRLTGLSPLRAP), had their biological activities evaluated. Both peptides had no effects on metallopeptidases [human neprilysin (NEP) and angiotensin-converting enzyme (ACE)] and acetylcholinesterase (AChE), and had no cytotoxic effects. Studies with PC12 neuronal cells showed that only α-campsomerin was able to enhance cell viability, while β-campsomerin had no effect. It is noteworthy that the only difference between the primary structures from these peptides is the presence of the AP extension at the C-terminus of β-campsomerin, compared to α-campsomerin. Among the linear α-helical peptides, annulatin (ISEALKSIIVG-NH₂) was evaluated for its biological activities. Annulatin showed histamine releasing activity from mast cells and low hemolytic activity, but no antimicrobial activities against all microbes tested were observed. Thus, in addition to providing unprecedented information on the whole components, the three peptides selected for the study suggest that molecules present in solitary scoliid wasp venoms may have interesting biological activities. Full article

(This article belongs to the Special Issue Toxinologic and Pharmacological Investigation of Venomous Arthropods)

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20 pages, 7135 KiB

Open AccessEditor’s ChoiceReview

Fish Cytolysins in All Their Complexity

by Fabiana V. Campos, Helena B. Fiorotti, Juliana B. Coitinho and Suely G. Figueiredo

Toxins 2021, 13(12), 877; https://doi.org/10.3390/toxins13120877 - 9 Dec 2021

Cited by 11 | Viewed by 3348

Abstract

The majority of the effects observed upon envenomation by scorpaenoid fish species can be reproduced by the cytolysins present in their venoms. Fish cytolysins are multifunctional proteins that elicit lethal, cytolytic, cardiovascular, inflammatory, nociceptive, and neuromuscular activities, representing a novel class of protein [...] Read more.

The majority of the effects observed upon envenomation by scorpaenoid fish species can be reproduced by the cytolysins present in their venoms. Fish cytolysins are multifunctional proteins that elicit lethal, cytolytic, cardiovascular, inflammatory, nociceptive, and neuromuscular activities, representing a novel class of protein toxins. These large proteins (MW 150–320 kDa) are composed by two different subunits, termed α and β, with about 700 amino acid residues each, being usually active in oligomeric form. There is a high degree of similarity between the primary sequences of cytolysins from different fish species. This suggests these molecules share similar mechanisms of action, which, at least regarding the cytolytic activity, has been proved to involve pore formation. Although the remaining components of fish venoms have interesting biological activities, fish cytolysins stand out because of their multifunctional nature and their ability to reproduce the main events of envenomation on their own. Considerable knowledge about fish cytolysins has been accumulated over the years, although there remains much to be unveiled. In this review, we compiled and compared the current information on the biochemical aspects and pharmacological activities of fish cytolysins, going over their structures, activities, mechanisms of action, and perspectives for the future. Full article

(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)

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20 pages, 4151 KiB

Open AccessEditor’s ChoiceArticle

Recombinant Production and Characterization of a New Toxin from Cryptops iheringi Centipede Venom Revealed by Proteome and Transcriptome Analysis

by Lhiri Hanna De Lucca Caetano, Milton Yutaka Nishiyama-Jr, Bianca de Carvalho Lins Fernandes Távora, Ursula Castro de Oliveira, Inácio de Loiola Meirelles Junqueira-de-Azevedo, Eliana L. Faquim-Mauro and Geraldo Santana Magalhães

Toxins 2021, 13(12), 858; https://doi.org/10.3390/toxins13120858 - 2 Dec 2021

Cited by 4 | Viewed by 3750

Abstract

Among the Chilopoda class of centipede, the Cryptops genus is one of the most associated with envenomation in humans in the metropolitan region of the state of São Paulo. To date, there is no study in the literature about the toxins present in [...] Read more.

Among the Chilopoda class of centipede, the Cryptops genus is one of the most associated with envenomation in humans in the metropolitan region of the state of São Paulo. To date, there is no study in the literature about the toxins present in its venom. Thus, in this work, a transcriptomic characterization of the Cryptops iheringi venom gland, as well as a proteomic analysis of its venom, were performed to obtain a toxin profile of this species. These methods indicated that 57.9% of the sequences showed to be putative toxins unknown in public databases; among them, we pointed out a novel putative toxin named Cryptoxin-1. The recombinant form of this new toxin was able to promote edema in mice footpads with massive neutrophils infiltration, linking this toxin to envenomation symptoms observed in accidents with humans. Our findings may elucidate the role of this toxin in the venom, as well as the possibility to explore other proteins found in this work. Full article

(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)

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11 pages, 883 KiB

Open AccessEditor’s ChoiceArticle

Infant Botulism: Checklist for Timely Clinical Diagnosis and New Possible Risk Factors Originated from a Case Report and Literature Review

by Robertino Dilena, Mattia Pozzato, Lucia Baselli, Giovanna Chidini, Sergio Barbieri, Concetta Scalfaro, Guido Finazzi, Davide Lonati, Carlo Alessandro Locatelli, Alberto Cappellari and Fabrizio Anniballi

Toxins 2021, 13(12), 860; https://doi.org/10.3390/toxins13120860 - 2 Dec 2021

Cited by 10 | Viewed by 4935

Abstract

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or [...] Read more.

Infant botulism is a rare and underdiagnosed disease caused by BoNT-producing clostridia that can temporarily colonize the intestinal lumen of infants less than one year of age. The diagnosis may be challenging because of its rareness, especially in patients showing atypical presentations or concomitant coinfections. In this paper, we report the first infant botulism case associated with Cytomegalovirus coinfection and transient hypogammaglobulinemia and discuss the meaning of these associations in terms of risk factors. Intending to help physicians perform the diagnosis, we also propose a practical clinical and diagnostic criteria checklist based on the revision of the literature. Full article

(This article belongs to the Special Issue Infant Botulism and Adult Intestinal Botulism)

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19 pages, 2856 KiB

Open AccessEditor’s ChoiceArticle

Evolution of the Ergot Alkaloid Biosynthetic Gene Cluster Results in Divergent Mycotoxin Profiles in Claviceps purpurea Sclerotia

by Carmen Hicks, Thomas E. Witte, Amanda Sproule, Tiah Lee, Parivash Shoukouhi, Zlatko Popovic, Jim G. Menzies, Christopher N. Boddy, Miao Liu and David P. Overy

Toxins 2021, 13(12), 861; https://doi.org/10.3390/toxins13120861 - 2 Dec 2021

Cited by 13 | Viewed by 4957

Abstract

Research into ergot alkaloid production in major cereal cash crops is crucial for furthering our understanding of the potential toxicological impacts of Claviceps purpurea upon Canadian agriculture and to ensure consumer safety. An untargeted metabolomics approach profiling extracts of C. purpurea sclerotia from [...] Read more.

Research into ergot alkaloid production in major cereal cash crops is crucial for furthering our understanding of the potential toxicological impacts of Claviceps purpurea upon Canadian agriculture and to ensure consumer safety. An untargeted metabolomics approach profiling extracts of C. purpurea sclerotia from four different grain crops separated the C. purpurea strains into two distinct metabolomic classes based on ergot alkaloid content. Variances in C. purpurea alkaloid profiles were correlated to genetic differences within the lpsA gene of the ergot alkaloid biosynthetic gene cluster from previously published genomes and from newly sequenced, long-read genome assemblies of Canadian strains. Based on gene cluster composition and unique polymorphisms, we hypothesize that the alkaloid content of C. purpurea sclerotia is currently undergoing adaptation. The patterns of lpsA gene diversity described in this small subset of Canadian strains provides a remarkable framework for understanding accelerated evolution of ergot alkaloid production in Claviceps purpurea. Full article

(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)

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33 pages, 9423 KiB

Open AccessEditor’s ChoiceReview

Isoflavones in Animals: Metabolism and Effects in Livestock and Occurrence in Feed

by Dino Grgic, Elisabeth Varga, Barbara Novak, Anneliese Müller and Doris Marko

Toxins 2021, 13(12), 836; https://doi.org/10.3390/toxins13120836 - 24 Nov 2021

Cited by 29 | Viewed by 5916

Abstract

Soybeans are a common ingredient of animal feed. They contain isoflavones, which are known to act as phytoestrogens in animals. Isoflavones were described to have beneficial effects on farm animals. However, there are also reports of negative outcomes after the consumption of isoflavones. [...] Read more.

Soybeans are a common ingredient of animal feed. They contain isoflavones, which are known to act as phytoestrogens in animals. Isoflavones were described to have beneficial effects on farm animals. However, there are also reports of negative outcomes after the consumption of isoflavones. This review summarizes the current knowledge of metabolization of isoflavones (including the influence of the microbiome, phase I and phase II metabolism), as well as the distribution of isoflavones and their metabolites in tissues. Furthermore, published studies on effects of isoflavones in livestock species (pigs, poultry, ruminants, fish) are reviewed. Moreover, published studies on occurrence of isoflavones in feed materials and co-occurrence with zearalenone are presented and are supplemented with our own survey data. Full article

(This article belongs to the Section Plant Toxins)

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18 pages, 1307 KiB

Open AccessEditor’s ChoiceReview

Lonomia obliqua Envenoming and Innovative Research

by Miryam Paola Alvarez-Flores, Renata Nascimento Gomes, Dilza Trevisan-Silva, Douglas Souza Oliveira, Isabel de Fátima Correia Batista, Marcus Vinicius Buri, Angela Maria Alvarez, Carlos DeOcesano-Pereira, Marcelo Medina de Souza and Ana Marisa Chudzinski-Tavassi

Toxins 2021, 13(12), 832; https://doi.org/10.3390/toxins13120832 - 23 Nov 2021

Cited by 9 | Viewed by 9348

Abstract

As a tribute to Butantan Institute in its 120th anniversary, this review describes some of the scientific research efforts carried out in the study of Lonomia envenoming in Brazil, a country where accidents with caterpillars reach over 42,000 individuals per year (especially in [...] Read more.

As a tribute to Butantan Institute in its 120th anniversary, this review describes some of the scientific research efforts carried out in the study of Lonomia envenoming in Brazil, a country where accidents with caterpillars reach over 42,000 individuals per year (especially in South and Southeast Brazil). Thus, the promising data regarding the studies with Lonomia’s toxins contributed to the creation of new research centers specialized in toxinology based at Butantan Institute, as well as to the production of the antilonomic serum (ALS), actions which are in line with the Butantan Institute mission “to research, develop, manufacture, and provide products and services for the health of the population”. In addition, the study of the components of the Lonomia obliqua bristle extract led to the discovery of new molecules with peculiar properties, opening a field of knowledge that could lead to the development and innovation of new drugs aimed at cell regeneration and inflammatory diseases. Full article

(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)

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13 pages, 2012 KiB

Open AccessEditor’s ChoiceArticle

Crotoxin Modulates Events Involved in Epithelial–Mesenchymal Transition in 3D Spheroid Model

by Ellen Emi Kato and Sandra Coccuzzo Sampaio

Toxins 2021, 13(11), 830; https://doi.org/10.3390/toxins13110830 - 22 Nov 2021

Cited by 6 | Viewed by 4296

Abstract

Epithelial–mesenchymal transition (EMT) occurs in the early stages of embryonic development and plays a significant role in the migration and the differentiation of cells into various types of tissues of an organism. However, tumor cells, with altered form and function, use the EMT [...] Read more.

Epithelial–mesenchymal transition (EMT) occurs in the early stages of embryonic development and plays a significant role in the migration and the differentiation of cells into various types of tissues of an organism. However, tumor cells, with altered form and function, use the EMT process to migrate and invade other tissues in the body. Several experimental (in vivo and in vitro) and clinical trial studies have shown the antitumor activity of crotoxin (CTX), a heterodimeric phospholipase A2 present in the Crotalus durissus terrificus venom. In this study, we show that CTX modulates the microenvironment of tumor cells. We have also evaluated the effect of CTX on the EMT process in the spheroid model. The invasion of type I collagen gels by heterospheroids (mix of MRC-5 and A549 cells constitutively prepared with 12.5 nM CTX), expression of EMT markers, and secretion of MMPs were analyzed. Western blotting analysis shows that CTX inhibits the expression of the mesenchymal markers, N-cadherin, α-SMA, and αv. This study provides evidence of CTX as a key modulator of the EMT process, and its antitumor action can be explored further for novel drug designing against metastatic cancer. Full article

(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)

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23 pages, 1901 KiB

Open AccessEditor’s ChoiceArticle

Lipid-Binding Aegerolysin from Biocontrol Fungus Beauveria bassiana

by Nada Kraševec, Anastasija Panevska, Špela Lemež, Jaka Razinger, Kristina Sepčić, Gregor Anderluh and Marjetka Podobnik

Toxins 2021, 13(11), 820; https://doi.org/10.3390/toxins13110820 - 20 Nov 2021

Cited by 7 | Viewed by 4181

Abstract

Fungi are the most common pathogens of insects and thus important regulators of their populations. Lipid-binding aegerolysin proteins, which are commonly found in the fungal kingdom, may be involved in several biologically relevant processes including attack and defense against other organisms. Aegerolysins act [...] Read more.

Fungi are the most common pathogens of insects and thus important regulators of their populations. Lipid-binding aegerolysin proteins, which are commonly found in the fungal kingdom, may be involved in several biologically relevant processes including attack and defense against other organisms. Aegerolysins act alone or together with membrane-attack-complex/perforin (MACPF)-like proteins to form transmembrane pores that lead to cell lysis. We performed an in-depth bioinformatics analysis of aegerolysins in entomopathogenic fungi and selected a candidate aegerolysin, beauveriolysin A (BlyA) from Beauveria bassiana. BlyA was expressed as a recombinant protein in Escherichia coli, and purified to further determine its functional and structural properties, including lipid-binding ability. Aegerolysins were found to be encoded in genomes of entomopathogenic fungi, such as Beauveria, Cordyceps, Metarhizium and Ophiocordyceps. Detailed bioinformatics analysis revealed that they are linked to MACPF-like genes in most genomes. We also show that BlyA interacts with an insect-specific membrane lipid. These results were placed in the context of other fungal and bacterial aegerolysins and their partner proteins. We believe that aegerolysins play a role in promoting the entomopathogenic and antagonistic activity of B. bassiana, which is an active ingredient of bioinsecticides. Full article

(This article belongs to the Special Issue Pore Forming Proteins: Structure, Function and Applications)

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19 pages, 2367 KiB

Open AccessEditor’s ChoiceReview

Microbiological Decontamination of Mycotoxins: Opportunities and Limitations

by Małgorzata Piotrowska

Toxins 2021, 13(11), 819; https://doi.org/10.3390/toxins13110819 - 19 Nov 2021

Cited by 51 | Viewed by 6360

Abstract

The contamination of food and feeds with mycotoxins poses a global health risk to humans and animals, with major economic consequences. Good agricultural and manufacturing practices can help control mycotoxin contamination. Since these actions are not always effective, several methods of decontamination have [...] Read more.

The contamination of food and feeds with mycotoxins poses a global health risk to humans and animals, with major economic consequences. Good agricultural and manufacturing practices can help control mycotoxin contamination. Since these actions are not always effective, several methods of decontamination have also been developed, including physical, chemical, and biological methods. Biological decontamination using microorganisms has revealed new opportunities. However, these biological methods require legal regulations and more research before they can be used in food production. Currently, only selected biological methods are acceptable for the decontamination of feed. This review discusses the literature on the use of microorganisms to remove mycotoxins and presents their possible mechanisms of action. Special attention is given to Saccharomyces cerevisiae yeast and lactic acid bacteria, and the use of yeast cell wall derivatives. Full article

(This article belongs to the Special Issue Mycotoxins: Toxicity and Biological Detoxification)

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11 pages, 1680 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

by Mieke Steenbeke, Sophie Valkenburg, Tessa Gryp, Wim Van Biesen, Joris R. Delanghe, Marijn M. Speeckaert and Griet Glorieux

Toxins 2021, 13(11), 809; https://doi.org/10.3390/toxins13110809 - 17 Nov 2021

Cited by 19 | Viewed by 5221

Abstract

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship [...] Read more.

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (r_s = 0.212; p = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p-cresol correlate with its derived plasma UTs (p-cresyl sulfate: r_s = 0.342, p < 0.001; p-cresyl glucuronide: r_s = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (r_s = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (r_s = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed. Full article

(This article belongs to the Special Issue Kidney Disease-Gut Dysbiosis: What Is the Role of Uremic Toxins?)

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14 pages, 2054 KiB

Open AccessEditor’s ChoiceArticle

Modulation of Adhesion Molecules Expression by Different Metalloproteases Isolated from Bothrops Snakes

by Bianca C. Zychar, Patrícia B. Clissa, Eneas Carvalho, Adilson S. Alves, Cristiani Baldo, Eliana L. Faquim-Mauro and Luís Roberto C. Gonçalves

Toxins 2021, 13(11), 803; https://doi.org/10.3390/toxins13110803 - 15 Nov 2021

Cited by 11 | Viewed by 3397

Abstract

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of [...] Read more.

Snake venom metalloproteinases (SVMP) are involved in local inflammatory reactions observed after snakebites. Based on domain composition, they are classified as PI (pro-domain + proteolytic domain), PII (PI + disintegrin-like domains), or PIII (PII + cysteine-rich domains). Here, we studied the role of different SVMPs domains in inducing the expression of adhesion molecules at the microcirculation of the cremaster muscle of mice. We used Jararhagin (Jar)—a PIII SVMP with intense hemorrhagic activity, and Jar-C—a Jar devoid of the catalytic domain, with no hemorrhagic activity, both isolated from B. jararaca venom and BnP-1—a weakly hemorrhagic P1 SVMP from B. neuwiedi venom. Toxins (0.5 µg) or PBS (100 µL) were injected into the scrotum of mice, and 2, 4, or 24 h later, the protein and gene expression of CD54 and CD31 in the endothelium, and integrins (CD11a and CD11b), expressed in leukocytes were evaluated. Toxins induced significant increases in CD54, CD11a, and CD11b at the initial time and a time-related increase in CD31 expression. In conclusion, our results suggest that, despite differences in hemorrhagic activities and domain composition of the SVMPs used in this study, they behave similarly to the induction of expression of adhesion molecules that promote leukocyte recruitment. Full article

(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)

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24 pages, 8524 KiB

Open AccessEditor’s ChoiceArticle

Mining Indole Alkaloid Synthesis Gene Clusters from Genomes of 53 Claviceps Strains Revealed Redundant Gene Copies and an Approximate Evolutionary Hourglass Model

by Miao Liu, Wendy Findlay, Jeremy Dettman, Stephen A. Wyka, Kirk Broders, Parivash Shoukouhi, Kasia Dadej, Miroslav Kolařík, Arpeace Basnyat and Jim G. Menzies

Toxins 2021, 13(11), 799; https://doi.org/10.3390/toxins13110799 - 13 Nov 2021

Cited by 7 | Viewed by 3192

Abstract

Ergot fungi (Claviceps spp.) are infamous for producing sclerotia containing a wide spectrum of ergot alkaloids (EA) toxic to humans and animals, making them nefarious villains in the agricultural and food industries, but also treasures for pharmaceuticals. In addition to three classes [...] Read more.

Ergot fungi (Claviceps spp.) are infamous for producing sclerotia containing a wide spectrum of ergot alkaloids (EA) toxic to humans and animals, making them nefarious villains in the agricultural and food industries, but also treasures for pharmaceuticals. In addition to three classes of EAs, several species also produce paspaline-derived indole diterpenes (IDT) that cause ataxia and staggers in livestock. Furthermore, two other types of alkaloids, i.e., loline (LOL) and peramine (PER), found in Epichloë spp., close relatives of Claviceps, have shown beneficial effects on host plants without evidence of toxicity to mammals. The gene clusters associated with the production of these alkaloids are known. We examined genomes of 53 strains of 19 Claviceps spp. to screen for these genes, aiming to understand the evolutionary patterns of these genes across the genus through phylogenetic and DNA polymorphism analyses. Our results showed (1) varied numbers of eas genes in C. sect. Claviceps and sect. Pusillae, none in sect. Citrinae, six idt/ltm genes in sect. Claviceps (except four in C. cyperi), zero to one partial (idtG) in sect. Pusillae, and four in sect. Citrinae, (2) two to three copies of dmaW, easE, easF, idt/ltmB, itd/ltmQ in sect. Claviceps, (3) frequent gene gains and losses, and (4) an evolutionary hourglass pattern in the intra-specific eas gene diversity and divergence in C. purpurea. Full article

(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)

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21 pages, 1132 KiB

Open AccessEditor’s ChoiceArticle

Genetic Responses and Aflatoxin Inhibition during Co-Culture of Aflatoxigenic and Non-Aflatoxigenic Aspergillus flavus

by Rebecca R. Sweany, Brian M. Mack, Geromy G. Moore, Matthew K. Gilbert, Jeffrey W. Cary, Matthew D. Lebar, Kanniah Rajasekaran and Kenneth E. Damann, Jr.

Toxins 2021, 13(11), 794; https://doi.org/10.3390/toxins13110794 - 11 Nov 2021

Cited by 15 | Viewed by 3871

Abstract

Aflatoxin is a carcinogenic mycotoxin produced by Aspergillus flavus. Non-aflatoxigenic (Non-tox) A. flavus isolates are deployed in corn fields as biocontrol because they substantially reduce aflatoxin contamination via direct replacement and additionally via direct contact or touch with toxigenic (Tox) isolates and [...] Read more.

Aflatoxin is a carcinogenic mycotoxin produced by Aspergillus flavus. Non-aflatoxigenic (Non-tox) A. flavus isolates are deployed in corn fields as biocontrol because they substantially reduce aflatoxin contamination via direct replacement and additionally via direct contact or touch with toxigenic (Tox) isolates and secretion of inhibitory/degradative chemicals. To understand touch inhibition, HPLC analysis and RNA sequencing examined aflatoxin production and gene expression of Non-tox isolate 17 and Tox isolate 53 mono-cultures and during their interaction in co-culture. Aflatoxin production was reduced by 99.7% in 72 h co-cultures. Fewer than expected unique reads were assigned to Tox 53 during co-culture, indicating its growth and/or gene expression was inhibited in response to Non-tox 17. Predicted secreted proteins and genes involved in oxidation/reduction were enriched in Non-tox 17 and co-cultures compared to Tox 53. Five secondary metabolite (SM) gene clusters and kojic acid synthesis genes were upregulated in Non-tox 17 compared to Tox 53 and a few were further upregulated in co-cultures in response to touch. These results suggest Non-tox strains can inhibit growth and aflatoxin gene cluster expression in Tox strains through touch. Additionally, upregulation of other SM genes and redox genes during the biocontrol interaction demonstrates a potential role of inhibitory SMs and antioxidants as additional biocontrol mechanisms and deserves further exploration to improve biocontrol formulations. Full article

(This article belongs to the Special Issue Current Status and Challenges of Aflatoxin Biocontrol Strategies)

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17 pages, 25855 KiB

Open AccessEditor’s ChoiceArticle

Varying Intensities of Introgression Obscure Incipient Venom-Associated Speciation in the Timber Rattlesnake (Crotalus horridus)

by Mark J. Margres, Kenneth P. Wray, Dragana Sanader, Preston J. McDonald, Lauren M. Trumbull, Austin H. Patton and Darin R. Rokyta

Toxins 2021, 13(11), 782; https://doi.org/10.3390/toxins13110782 - 5 Nov 2021

Cited by 9 | Viewed by 4195

Abstract

Ecologically divergent selection can lead to the evolution of reproductive isolation through the process of ecological speciation, but the balance of responsible evolutionary forces is often obscured by an inadequate assessment of demographic history and the genetics of traits under selection. Snake venoms [...] Read more.

Ecologically divergent selection can lead to the evolution of reproductive isolation through the process of ecological speciation, but the balance of responsible evolutionary forces is often obscured by an inadequate assessment of demographic history and the genetics of traits under selection. Snake venoms have emerged as a system for studying the genetic basis of adaptation because of their genetic tractability and contributions to fitness, and speciation in venomous snakes can be associated with ecological diversification such as dietary shifts and corresponding venom changes. Here, we explored the neurotoxic (type A)–hemotoxic (type B) venom dichotomy and the potential for ecological speciation among Timber Rattlesnake (Crotalus horridus) populations. Previous work identified the genetic basis of this phenotypic difference, enabling us to characterize the roles geography, history, ecology, selection, and chance play in determining when and why new species emerge or are absorbed. We identified significant genetic, proteomic, morphological, and ecological/environmental differences at smaller spatial scales, suggestive of incipient ecological speciation between type A and type B C. horridus. Range-wide analyses, however, rejected the reciprocal monophyly of venom type, indicative of varying intensities of introgression and a lack of reproductive isolation across the range. Given that we have now established the phenotypic distributions and ecological niche models of type A and B populations, genome-wide data are needed and capable of determining whether type A and type B C. horridus represent distinct, reproductively isolated lineages due to incipient ecological speciation or differentiated populations within a single species. Full article

(This article belongs to the Special Issue Using Genomics to Understand Venom Evolution)

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16 pages, 884 KiB

Open AccessEditor’s ChoiceArticle

Role of Sesamia nonagrioides and Ostrinia nubilalis as Vectors of Fusarium spp. and Contribution of Corn Borer-Resistant Bt Maize to Mycotoxin Reduction

by María Arias-Martín, Miriam Haidukowski, Gema P. Farinós and Belén Patiño

Toxins 2021, 13(11), 780; https://doi.org/10.3390/toxins13110780 - 4 Nov 2021

Cited by 11 | Viewed by 3885

Abstract

Maize expressing Cry1Ab insecticidal toxin (Bt maize) is an effective method to control Sesamia nonagrioides and Ostrinia nubilalis, the most damaging corn borers of southern Europe. In this area, maize is prone to Fusarium infections, which can produce mycotoxins that pose a [...] Read more.

Maize expressing Cry1Ab insecticidal toxin (Bt maize) is an effective method to control Sesamia nonagrioides and Ostrinia nubilalis, the most damaging corn borers of southern Europe. In this area, maize is prone to Fusarium infections, which can produce mycotoxins that pose a serious risk to human and animal health, causing significant economic losses in the agrifood industry. To investigate the influence of corn borer damage on the presence of Fusarium species and their mycotoxins, Bt maize ears and insect-damaged ears of non-Bt maize were collected from commercial fields in three Bt maize growing areas in Spain, and differences in contamination were assessed. Additionally, larvae of both borer species were collected to evaluate their role as vectors of these molds. Non-Bt maize ears showed significantly higher presence of F. verticillioides, F. proliferatum, and F. subglutinans than Bt maize ears. For the first time, Fusarium species have been isolated from larvae of the two species. The most frequently found mycotoxins in ears were fumonisins, with non-Bt ears being significantly more contaminated than those of Bt maize. High levels of fumonisins were shown to correlate with the occurrence of corn borers in the ear and the presence of F. verticillioides and F. proliferatum. Full article

(This article belongs to the Special Issue Occurrence and Integrated Management of Mycotoxins)

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27 pages, 3293 KiB

Open AccessEditor’s ChoiceArticle

Depuration Kinetics and Growth Dilution of Caribbean Ciguatoxin in the Omnivore Lagodon rhomboides: Implications for Trophic Transfer and Ciguatera Risk

by Clayton T. Bennett and Alison Robertson

Toxins 2021, 13(11), 774; https://doi.org/10.3390/toxins13110774 - 1 Nov 2021

Cited by 15 | Viewed by 4317

Abstract

Modeling ciguatoxin (CTX) trophic transfer in marine food webs has significant implications for the management of ciguatera poisoning, a circumtropical disease caused by human consumption of CTX-contaminated seafood. Current models associated with CP risk rely on modeling abundance/presence of CTX-producing epi-benthic dinoflagellates, e.g., [...] Read more.

Modeling ciguatoxin (CTX) trophic transfer in marine food webs has significant implications for the management of ciguatera poisoning, a circumtropical disease caused by human consumption of CTX-contaminated seafood. Current models associated with CP risk rely on modeling abundance/presence of CTX-producing epi-benthic dinoflagellates, e.g., Gambierdiscus spp., and are based on studies showing that toxin production is site specific and occurs in pulses driven by environmental factors. However, food web models are not yet developed and require parameterizing the CTX exposure cascade in fish which has been traditionally approached through top-down assessment of CTX loads in wild-caught fish. The primary goal of this study was to provide critical knowledge on the kinetics of C-CTX-1 bioaccumulation and depuration in the marine omnivore Lagodon rhomboides. We performed a two-phase, 17 week CTX feeding trial in L. rhomboides where fish were given either a formulated C-CTX-1 (n = 40) or control feed (n = 37) for 20 days, and then switched to a non-toxic diet for up to 14 weeks. Fish were randomly sampled through time with whole muscle, liver, and other pooled viscera dissected for toxin analysis by a sodium channel-dependent MTT-based mouse neuroblastoma (N2a) assay. The CTX levels measured in all tissues increased with time during the exposure period (days 1 to 20), but a decrease in CTX-specific toxicity with depuration time only occurred in viscera extracts. By the end of the depuration, muscle, liver, and viscera samples had mean toxin concentrations of 189%, 128%, and 42%, respectively, compared to fish sampled at the start of the depuration phase. However, a one-compartment model analysis of combined tissues showed total concentration declined to 56%, resulting in an approximate half-life of 97 d (R² = 0.43). Further, applying growth dilution correction models to the overall concentration found that growth was a major factor reducing C-CTX concentrations, and that the body burden was largely unchanged, causing pseudo-elimination and a half-life of 143–148 days (R² = 0.36). These data have important implications for food web CTX models and management of ciguatera poisoning in endemic regions where the frequency of environmental algal toxin pulses may be greater than the growth-corrected half-life of C-CTX in intermediate-trophic-level fish with high site fidelity. Full article

(This article belongs to the Special Issue Ciguatoxins)

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14 pages, 2603 KiB

Open AccessEditor’s ChoiceArticle

Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials

by Ping-Hsun Lu, Hui-En Chuo, Ko-Lin Kuo, Jian-Fu Liao and Po-Hsuan Lu

Toxins 2021, 13(11), 769; https://doi.org/10.3390/toxins13110769 - 30 Oct 2021

Cited by 8 | Viewed by 4190

Abstract

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the [...] Read more.

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = −3.52, 95% confidence interval = −5.63 to −1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease. Full article

(This article belongs to the Special Issue Pathogenesis and Therapy of Chronic Kidney Disease-Associated Itch (Uremic Pruritus))

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16 pages, 1101 KiB

Open AccessEditor’s ChoiceArticle

Strong Alterations in the Sphingolipid Profile of Chickens Fed a Dose of Fumonisins Considered Safe

by Didier Tardieu, Maria Matard-Mann, Pi Nyvall Collén and Philippe Guerre

Toxins 2021, 13(11), 770; https://doi.org/10.3390/toxins13110770 - 30 Oct 2021

Cited by 16 | Viewed by 2983

Abstract

Fumonisins (FB) are mycotoxins known to exert most of their toxicity by blocking ceramide synthase, resulting in disruption of sphingolipid metabolism. Although the effects of FB on sphinganine (Sa) and sphingosine (So) are well documented in poultry, little information is available on their [...] Read more.

Fumonisins (FB) are mycotoxins known to exert most of their toxicity by blocking ceramide synthase, resulting in disruption of sphingolipid metabolism. Although the effects of FB on sphinganine (Sa) and sphingosine (So) are well documented in poultry, little information is available on their other effects on sphingolipids. The objective of this study was to analyze the effects of FB on the hepatic and plasma sphingolipidome in chickens. The first concern of this analysis was to clarify the effects of FB on hepatic sphingolipid levels, whose variations can lead to numerous toxic manifestations. The second was to specify the possible use of an alteration of the sphingolipidome as a biomarker of exposure to FB, in addition to the measurement of the Sa:So ratio already widely used. For this purpose, we developed an UHPLC MS/MS method that enabled the determination of 82 SL, including 10 internal standards, in chicken liver and plasma. The validated method was used to measure the effects of FB administered to chickens at a dose close to 20 mg FB1 + FB2/kg feed for 9 days. Significant alterations of sphingoid bases, ceramides, dihydroceramides, glycosylceramides, sphingomyelins and dihydrosphingomyelins were observed in the liver. In addition, significant increases in plasma sphinganine 1-phosphate, sphingosine 1-phosphate and sphingomyelins were observed in plasma. Interestingly, partial least-squares discriminant analysis of 11 SL in plasma made it possible to discriminate exposed chickens from control chickens, whereas analysis of Sa and So alone revealed no difference. In conclusion, our results show that the effects of FB in chickens are complex, and that SL profiling enables the detection of exposure to FB when Sa and So fail. Full article

(This article belongs to the Special Issue Effects of Mycotoxins on Health and Performance in Animals)

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33 pages, 1184 KiB

Open AccessEditor’s ChoiceReview

Updated Review of the Toxicity of Selected Fusarium Toxins and Their Modified Forms

by Adam Pierzgalski, Marcin Bryła, Joanna Kanabus, Marta Modrzewska and Grażyna Podolska

Toxins 2021, 13(11), 768; https://doi.org/10.3390/toxins13110768 - 29 Oct 2021

Cited by 36 | Viewed by 5191

Abstract

Mycotoxins are one of the most dangerous food and feed contaminants, hence they have significant influence on human and animal health. This study reviews the information reported over the last few years on the toxic effects of the most relevant and studied Fusarium [...] Read more.

Mycotoxins are one of the most dangerous food and feed contaminants, hence they have significant influence on human and animal health. This study reviews the information reported over the last few years on the toxic effects of the most relevant and studied Fusarium toxins and their modified forms. Deoxynivalenol (DON) and its metabolites can induce intracellular oxidative stress, resulting in DNA damage. Recent studies have also revealed the capability of DON and its metabolites to disturb the cell cycle and alter amino acid expression. Several studies have attempted to explore the mechanism of action of T-2 and HT-2 toxins in anorexia induction. Among other findings, two neurotransmitters associated with this process have been identified, namely substance P and serotonin (5-hydroxytryptamine). For zearalenone (ZEN) and its metabolites, the literature points out that, in addition to their generally acknowledged estrogenic and oxidative potentials, they can also modify DNA by altering methylation patterns and histone acetylation. The ability of the compounds to induce alterations in the expression of major metabolic genes suggests that these compounds can contribute to the development of numerous metabolic diseases, including type 2 diabetes. Full article

(This article belongs to the Section Mycotoxins)

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23 pages, 6833 KiB

Open AccessEditor’s ChoiceArticle

Twenty-Five Years of Domoic Acid Monitoring in Galicia (NW Spain): Spatial, Temporal and Interspecific Variations

by Juan Blanco, Ángeles Moroño, Fabiola Arévalo, Jorge Correa, Covadonga Salgado, Araceli E. Rossignoli and J. Pablo Lamas

Toxins 2021, 13(11), 756; https://doi.org/10.3390/toxins13110756 - 25 Oct 2021

Cited by 13 | Viewed by 3009

Abstract

Prevalence, impact on shellfish resources and interspecific, spatial, and temporal variabilities of domoic acid (DA) in bivalves from Galicia (NW Spain) have been studied based on more than 25 years of monitoring data. The maximum prevalence (samples in which DA was detected) (100%) [...] Read more.

Prevalence, impact on shellfish resources and interspecific, spatial, and temporal variabilities of domoic acid (DA) in bivalves from Galicia (NW Spain) have been studied based on more than 25 years of monitoring data. The maximum prevalence (samples in which DA was detected) (100%) and incidence (samples with DA levels above the regulatory limit) (97.4%) were recorded in Pecten maximus, and the minimum ones in Mytilus galloprovincialis (12.6 and 1.1%, respectively). The maximum DA concentrations were 663.9 mg kg⁻¹ in P. maximus and 316 mg kg⁻¹ in Venerupis corrugata. After excluding scallop P. maximus data, DA was found (prevalence) in 13.3% of bivalve samples, with 1.3% being over the regulatory limit. In general, the prevalence of this toxin decreased towards the North but not the magnitude of its episodes. The seasonal distribution was characterized by two maxima, in spring and autumn, with the later decreasing in intensity towards the north. DA levels decreased slightly over the studied period, although this decreasing trend was not linear. A cyclic pattern was observed in the interannual variability, with cycles of 4 and 11 years. Intoxication and detoxification rates were slower than those expected from laboratory experiments, suggesting the supply of DA during these phases plays an important role. Full article

(This article belongs to the Special Issue Monitoring of Marine Biotoxins)

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17 pages, 890 KiB

Open AccessEditor’s ChoiceReview

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

by Siro Luvisetto

Toxins 2021, 13(11), 751; https://doi.org/10.3390/toxins13110751 - 22 Oct 2021

Cited by 39 | Viewed by 11667

Abstract

Botulinum neurotoxins (BoNTs) are potent inhibitors of synaptic vesicle fusion and transmitter release. The natural target of BoNTs is the peripheral neuromuscular junction (NMJ) where, by blocking the release of acetylcholine (ACh), they functionally denervate muscles and alter muscle tone. This leads them [...] Read more.

Botulinum neurotoxins (BoNTs) are potent inhibitors of synaptic vesicle fusion and transmitter release. The natural target of BoNTs is the peripheral neuromuscular junction (NMJ) where, by blocking the release of acetylcholine (ACh), they functionally denervate muscles and alter muscle tone. This leads them to be an excellent drug for the therapy of muscle hyperactivity disorders, such as dystonia, spasticity, and many other movement disorders. BoNTs are also effective in inhibiting both the release of ACh at sites other than NMJ and the release of neurotransmitters other than ACh. Furthermore, much evidence shows that BoNTs can act not only on the peripheral nervous system (PNS), but also on the central nervous system (CNS). Under this view, central changes may result either from sensory input from the PNS, from retrograde transport of BoNTs, or from direct injection of BoNTs into the CNS. The aim of this review is to give an update on available data, both from animal models or human studies, which suggest or confirm central alterations induced by peripheral or central BoNTs treatment. The data will be discussed with particular attention to the possible therapeutic applications to pathological conditions and degenerative diseases of the CNS. Full article

(This article belongs to the Special Issue The Role of Botulinum and Other Clostridial Neurotoxins in Central Nervous System)

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18 pages, 13768 KiB

Open AccessEditor’s ChoiceArticle

Tetrodotoxins in French Bivalve Mollusks—Analytical Methodology, Environmental Dynamics and Screening of Bacterial Strain Collections

by Damien Réveillon, Véronique Savar, Estelle Schaefer, Julien Chevé, Marie-Pierre Halm-Lemeille, Dominique Hervio-Heath, Marie-Agnès Travers, Eric Abadie, Jean-Luc Rolland and Philipp Hess

Toxins 2021, 13(11), 740; https://doi.org/10.3390/toxins13110740 - 20 Oct 2021

Cited by 17 | Viewed by 4164

Abstract

Tetrodotoxins (TTXs) are potentially lethal paralytic toxins that have been identified in European shellfish over recent years. Risk assessment has suggested comparatively low levels (44 µg TTX-equivalent/kg) but stresses the lack of data on occurrence. Both bacteria and dinoflagellates were suggested as possible [...] Read more.

Tetrodotoxins (TTXs) are potentially lethal paralytic toxins that have been identified in European shellfish over recent years. Risk assessment has suggested comparatively low levels (44 µg TTX-equivalent/kg) but stresses the lack of data on occurrence. Both bacteria and dinoflagellates were suggested as possible biogenic sources, either from an endogenous or exogenous origin. We thus investigated TTXs in (i) 98 shellfish samples and (ii) 122 bacterial strains, isolated from French environments. We optimized a method based on mass spectrometry, using a single extraction step followed by ultrafiltration without Solid Phase Extraction and matrix-matched calibration for both shellfish and bacterial matrix. Limits of detection and quantification were 6.3 and 12.5 µg/kg for shellfish and 5.0 and 10 µg/kg for bacterial matrix, respectively. Even though bacterial matrix resulted in signal enhancement, no TTX analog was detected in any strain. Bivalves (either Crassostrea gigas or Ruditapes philippinarum) were surveyed in six French production areas over 2.5–3 month periods (2018–2019). Concentrations of TTX ranged from ‘not detected’ to a maximum of 32 µg/kg (Bay of Brest, 17 June 2019), with events lasting 2 weeks at maximum. While these results are in line with previous studies, they provide new data of TTX occurrence and confirm that the link between bacteria, bivalves and TTX is complex. Full article

(This article belongs to the Special Issue Marine Toxins and Food Safety)

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25 pages, 9469 KiB

Open AccessEditor’s ChoiceArticle

Modelling the Effects of Weather Conditions on Cereal Grain Contamination with Deoxynivalenol in the Baltic Sea Region

by Katarzyna Marzec-Schmidt, Thomas Börjesson, Skaidre Suproniene, Małgorzata Jędryczka, Sigita Janavičienė, Tomasz Góral, Ida Karlsson, Yuliia Kochiieru, Piotr Ochodzki, Audronė Mankevičienė and Kristin Piikki

Toxins 2021, 13(11), 737; https://doi.org/10.3390/toxins13110737 - 20 Oct 2021

Cited by 12 | Viewed by 3538

Abstract

Fusarium head blight (FHB) is one of the most serious diseases of small-grain cereals worldwide, resulting in yield reduction and an accumulation of the mycotoxin deoxynivalenol (DON) in grain. Weather conditions are known to have a significant effect on the ability of fusaria [...] Read more.

Fusarium head blight (FHB) is one of the most serious diseases of small-grain cereals worldwide, resulting in yield reduction and an accumulation of the mycotoxin deoxynivalenol (DON) in grain. Weather conditions are known to have a significant effect on the ability of fusaria to infect cereals and produce toxins. In the past 10 years, severe outbreaks of FHB, and grain DON contamination exceeding the EU health safety limits, have occurred in countries in the Baltic Sea region. In this study, extensive data from field trials in Sweden, Poland and Lithuania were analysed to identify the most crucial weather variables for the ability of Fusarium to produce DON. Models were developed for the prediction of DON contamination levels in harvested grain exceeding 200 µg kg⁻¹ for oats, spring barley and spring wheat in Sweden and winter wheat in Poland, and 1250 µg kg⁻¹ for spring wheat in Lithuania. These models were able to predict high DON levels with an accuracy of 70–81%. Relative humidity (RH) and precipitation (PREC) were identified as the weather factors with the greatest influence on DON accumulation in grain, with high RH and PREC around flowering and later in grain development and ripening correlated with high DON levels. High temperatures during grain development and senescence reduced the risk of DON accumulation. The performance of the models, based only on weather variables, was relatively accurate. In future studies, it might be of interest to determine whether inclusion of variables such as pre-crop, agronomic factors and crop resistance to FHB could further improve the performance of the models. Full article

(This article belongs to the Special Issue Fusarium Toxins: Occurrence, Risk and Reduction)

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16 pages, 992 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Performance of Lateral Flow Devices for Total Aflatoxins with Special Emphasis on Their Robustness under Sub-Saharan Conditions

by Barbara Cvak, Benedikt Warth, Joseph Atehnkeng, Alexandra Parich, Alexandra Moritz, Michael Sulyok and Rudolf Krska

Toxins 2021, 13(11), 742; https://doi.org/10.3390/toxins13110742 - 20 Oct 2021

Cited by 7 | Viewed by 4594

Abstract

As aflatoxins are a global risk for humans and animals, testing methods for rapid on-site screening are increasingly needed alongside the standard analytical laboratory tools. In the presented study, lateral flow devices (LFDs) for rapid total aflatoxin screening were thoroughly investigated with respect [...] Read more.

As aflatoxins are a global risk for humans and animals, testing methods for rapid on-site screening are increasingly needed alongside the standard analytical laboratory tools. In the presented study, lateral flow devices (LFDs) for rapid total aflatoxin screening were thoroughly investigated with respect to their matrix effects, cross-reactivity, their performance under harsh conditions in Sub-Saharan Africa (SSA), and their stability, as well as when compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS). To analyze the matrix effects, qualitative test kits offering a certain cutoff level were used to screen different nut samples. In addition, these tests were challenged on their cross-reactivity with 230 fungal toxins and metabolites. Furthermore, the resulting measurements performed under harsh tropical conditions (up to 38.4 °C and 91% relative humidity) in SSA, specifically Burkina Faso and Mozambique, were compared with the results from a well-established and validated LC-MS/MS-based reference method. The comparison of the on-site LFD results with the reference method showed a good agreement: 86.4% agreement, 11.8% non-agreement, and 1.8% invalid test results. To test the robustness of the cutoff tests, short- and long-term stability testing was carried out in Mozambique and Nigeria. For both experiments, no loss of test performance could be determined. Finally, a subset of African corn samples was shipped to Austria and analyzed under laboratory conditions using semiquantitative aflatoxin tests. A good correlation was found between the rapid strip tests and the LC-MS/MS reference method. Overall, the evaluated LFDs showed satisfying results regarding their cross-reactivity, matrix effects, stability, and robustness. Full article

(This article belongs to the Special Issue Reduction and Control of Mycotoxins along Entire Food and Feed Chain)

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13 pages, 1641 KiB

Open AccessEditor’s ChoiceArticle

Salinity Affects Saxitoxins (STXs) Toxicity in the Dinoflagellate Alexandrium pacificum, with Low Transcription of SXT-Biosynthesis Genes sxtA4 and sxtG

by Quynh Thi Nhu Bui, Hansol Kim, Hyunjun Park and Jang-Seu Ki

Toxins 2021, 13(10), 733; https://doi.org/10.3390/toxins13100733 - 18 Oct 2021

Cited by 24 | Viewed by 3924

Abstract

Salinity is an important factor for regulating metabolic processes in aquatic organisms; however, its effects on toxicity and STX biosynthesis gene responses in dinoflagellates require further elucidation. Herein, we evaluated the physiological responses, toxin production, and expression levels of two STX synthesis core [...] Read more.

Salinity is an important factor for regulating metabolic processes in aquatic organisms; however, its effects on toxicity and STX biosynthesis gene responses in dinoflagellates require further elucidation. Herein, we evaluated the physiological responses, toxin production, and expression levels of two STX synthesis core genes, sxtA4 and sxtG, in the dinoflagellate Alexandrium pacificum Alex05 under different salinities (20, 25, 30, 35, and 40 psu). Optimal growth was observed at 30 psu (0.12 cell division/d), but cell growth significantly decreased at 20 psu and was irregular at 25 and 40 psu. The cell size increased at lower salinities, with the highest size of 31.5 µm at 20 psu. STXs eq was highest (35.8 fmol/cell) in the exponential phase at 30 psu. GTX4 and C2 were predominant at that time but were replaced by GTX1 and NeoSTX in the stationary phase. However, sxtA4 and sxtG mRNAs were induced, and their patterns were similar in all tested conditions. PCA showed that gene transcriptional levels were not correlated with toxin contents and salinity. These results suggest that A. pacificum may produce the highest amount of toxins at optimal salinity, but sxtA4 and sxtG may be only minimally affected by salinity, even under high salinity stress. Full article

(This article belongs to the Special Issue Marine Phytoplankton Toxins: Genomics, Distribution and Risk Assessment)

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11 pages, 1463 KiB

Open AccessEditor’s ChoiceArticle

Tetrodotoxin/Saxitoxins Selectivity of the Euryhaline Freshwater Pufferfish Dichotomyctere fluviatilis

by Hongchen Zhu, Towa Sakai, Yuji Nagashima, Hiroyuki Doi, Tomohiro Takatani and Osamu Arakawa

Toxins 2021, 13(10), 731; https://doi.org/10.3390/toxins13100731 - 16 Oct 2021

Cited by 5 | Viewed by 4030

Abstract

The present study evaluated differences in the tetrodotoxin (TTX)/saxitoxins (STXs) selectivity between marine and freshwater pufferfish by performing in vivo and in vitro experiments. In the in vivo experiment, artificially reared nontoxic euryhaline freshwater pufferfish Dichotomyctere fluviatilis were intrarectally administered a mixture of [...] Read more.

The present study evaluated differences in the tetrodotoxin (TTX)/saxitoxins (STXs) selectivity between marine and freshwater pufferfish by performing in vivo and in vitro experiments. In the in vivo experiment, artificially reared nontoxic euryhaline freshwater pufferfish Dichotomyctere fluviatilis were intrarectally administered a mixture of TTX (24 nmol/fish) and STX (20 nmol/fish). The amount of toxin in the intestine, liver, muscle, gonads, and skin was quantified at 24, 48, and 72 h. STX was detected in the intestine over a long period of time, with some (2.7–6.1% of the given dose) being absorbed into the body and temporarily located in the liver. Very little TTX was retained in the body. In the in vitro experiments, slices of intestine, liver, and skin tissue prepared from artificially reared nontoxic D. fluviatilis and the marine pufferfish Takifugu rubripes were incubated in buffer containing TTX and STXs (20 nmol/mL each) for up to 24 or 72 h, and the amount of toxin taken up in the tissue was quantified over time. In contrast to T. rubripes, the intestine, liver, and skin tissues of D. fluviatilis selectively took up only STXs. These findings indicate that the TTX/STXs selectivity differs between freshwater and marine pufferfish. Full article

(This article belongs to the Special Issue Monitoring of Marine Biotoxins)

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14 pages, 2008 KiB

Open AccessEditor’s ChoiceArticle

Effects of Deoxynivalenol and Fumonisins Fed in Combination to Beef Cattle: Immunotoxicity and Gene Expression

by Heaven L. Roberts, Massimo Bionaz, Duo Jiang, Barbara Doupovec, Johannes Faas, Charles T. Estill, Dian Schatzmayr and Jennifer M. Duringer

Toxins 2021, 13(10), 714; https://doi.org/10.3390/toxins13100714 - 10 Oct 2021

Cited by 10 | Viewed by 3079

Abstract

We evaluated the effects of a treatment diet contaminated with 1.7 mg deoxynivalenol and 3.5 mg fumonisins (B1, B2 and B3) per kg ration on immune status and peripheral blood gene expression profiles in finishing-stage Angus steers. The mycotoxin treatment diet was fed [...] Read more.

We evaluated the effects of a treatment diet contaminated with 1.7 mg deoxynivalenol and 3.5 mg fumonisins (B1, B2 and B3) per kg ration on immune status and peripheral blood gene expression profiles in finishing-stage Angus steers. The mycotoxin treatment diet was fed for a period of 21 days followed by a two-week washout period during which time all animals consumed the control diet. Whole-blood leukocyte differentials were performed weekly throughout the experimental and washout period. Comparative profiles of CD4⁺ and CD8⁺ T cells, along with bactericidal capacity of circulating neutrophils and monocytes were evaluated at 0, 7, 14, 21 and 35 days. Peripheral blood gene expression was measured at 0, 7, 21 and 35 days via RNA sequencing. Significant increases in the percentage of CD4⁻CD8⁺ T cells were observed in treatment-fed steers after two weeks of treatment and were associated with decreased CD4:CD8 T-cell ratios at this same timepoint (p ≤ 0.10). No significant differences were observed as an effect of treatment in terms of bactericidal capacity at any timepoint. Dietary treatments induced major changes in transcripts associated with endocrine, metabolic and infectious diseases; protein digestion and absorption; and environmental information processing (inhibition of signaling and processing), as evaluated by dynamic impact analysis. DAVID analysis also suggested treatment effects on oxygen transport, extra-cellular signaling, cell membrane structure and immune system function. These results indicate that finishing-stage beef cattle are susceptible to the immunotoxic and transcript-inhibitory effects of deoxynivalenol and fumonisins at levels which may be realistically encountered in feedlot situations. Full article

(This article belongs to the Special Issue Effects of Mycotoxins on Health and Performance in Animals)

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16 pages, 2273 KiB

Open AccessEditor’s ChoiceReview

Undercover Agents of Infection: The Stealth Strategies of T4SS-Equipped Bacterial Pathogens

by Arthur Bienvenu, Eric Martinez and Matteo Bonazzi

Toxins 2021, 13(10), 713; https://doi.org/10.3390/toxins13100713 - 9 Oct 2021

Cited by 6 | Viewed by 3466

Abstract

Intracellular bacterial pathogens establish their replicative niches within membrane-encompassed compartments, called vacuoles. A subset of these bacteria uses a nanochannel called the type 4 secretion system (T4SS) to inject effector proteins that subvert the host cell machinery and drive the biogenesis of these [...] Read more.

Intracellular bacterial pathogens establish their replicative niches within membrane-encompassed compartments, called vacuoles. A subset of these bacteria uses a nanochannel called the type 4 secretion system (T4SS) to inject effector proteins that subvert the host cell machinery and drive the biogenesis of these compartments. These bacteria have also developed sophisticated ways of altering the innate immune sensing and response of their host cells, which allow them to cause long-lasting infections and chronic diseases. This review covers the mechanisms employed by intravacuolar pathogens to escape innate immune sensing and how Type 4-secreted bacterial effectors manipulate host cell mechanisms to allow the persistence of bacteria. Full article

(This article belongs to the Special Issue Bacterial Secretion Systems, Anti-host Effectors and Toxins: Towards the New Microbiology)

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13 pages, 3908 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Penicillium expansum Impact and Patulin Accumulation on Conventional and Traditional Apple Cultivars

by Ante Lončarić, Bojan Šarkanj, Ana-Marija Gotal, Marija Kovač, Ante Nevistić, Goran Fruk, Martina Skendrović Babojelić, Jurislav Babić, Borislav Miličević and Tihomir Kovač

Toxins 2021, 13(10), 703; https://doi.org/10.3390/toxins13100703 - 4 Oct 2021

Cited by 21 | Viewed by 6811

Abstract

Penicillium expansum is a necrotrophic plant pathogen among the most ubiquitous fungi disseminated worldwide. It causes blue mould rot in apples during storage, transport and sale, threatening human health by secreting patulin, a toxic secondary metabolite that contaminates apples and apple-derived products. Nevertheless, [...] Read more.

Penicillium expansum is a necrotrophic plant pathogen among the most ubiquitous fungi disseminated worldwide. It causes blue mould rot in apples during storage, transport and sale, threatening human health by secreting patulin, a toxic secondary metabolite that contaminates apples and apple-derived products. Nevertheless, there is still a lack of sufficient data regarding the resistance of different apple cultivars to P. expansum, especially ancient ones, which showed to possess certain resistance to plant diseases. In this work, we investigated the polyphenol profile of 12 traditional and 8 conventional apple cultivar and their resistance to P. expansum CBS 325.48. Eight polyphenolic compounds were detected; the most prominent were catechin, epicatechin and gallic acid. The highest content of catechin was detected in ‘Apistar’—91.26 mg/100 g of fresh weight (FW), epicatechin in ‘Bobovac’—67.00 mg/100 g of FW, and gallic acid in ‘Bobovac’ and ‘Kraljevčica’—8.35 and 7.40 mg/100 g of FW, respectively. The highest content of patulin was detected in ‘Kraljevčica’ followed by ‘Apistar’—1687 and 1435 µg/kg, respectively. In apple cultivars ‘Brčko’, ‘Adamčica’ and ‘Idared’, patulin was not detected. Furthermore, the patulin content was positively correlated with gallic acid (r = 0.4226; p = 0.002), catechin (r = 0.3717; p = 0.008) and epicatechin (r = 0.3305; p = 0.019). This fact indicates that higher contents of gallic acid, catechin and epicatechin negatively affected and boost patulin concentration in examined apple cultivars. This can be related to the prooxidant activity of polyphenolic compounds and sensitivity of P. expansum to the disturbance of oxidative status. Full article

(This article belongs to the Special Issue Environmental Stress on the Production of Mycotoxins)

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13 pages, 678 KiB

Open AccessEditor’s ChoiceArticle

Fumonisin B1 Accumulates in Chicken Tissues over Time and This Accumulation Was Reduced by Feeding Algo-Clay

by Julia Laurain, Didier Tardieu, Maria Matard-Mann, Maria Angeles Rodriguez and Philippe Guerre

Toxins 2021, 13(10), 701; https://doi.org/10.3390/toxins13100701 - 2 Oct 2021

Cited by 24 | Viewed by 4028

Abstract

The toxicokinetics of the food and feed contaminant Fumonisin B (FB) are characterized by low oral absorption and rapid plasma elimination. For these reasons, FB is not considered to accumulate in animals. However, recent studies in chicken and turkey showed that, in these [...] Read more.

The toxicokinetics of the food and feed contaminant Fumonisin B (FB) are characterized by low oral absorption and rapid plasma elimination. For these reasons, FB is not considered to accumulate in animals. However, recent studies in chicken and turkey showed that, in these species, the hepatic half-elimination time of fumonisin B1 (FB1) was several days, suggesting that FB1 may accumulate in the body. For the present study, 21-day-old chickens received a non-toxic dose of around 20 mg FB1 + FB2/kg of feed to investigate whether FB can accumulate in the body over time. Measurements taken after four and nine days of exposure revealed increased concentrations of sphinganine (Sa) and sphingosine (So) over time in the liver, but no sign of toxicity and no effect on performances were observed at this level of FB in feed. Measurements of FB in tissues showed that FB1 accumulated in chicken livers from four to nine days, with concentrations of 20.3 and 32.1 ng FB1/g observed, respectively, at these two exposure periods. Fumonisin B2 (FB2) also accumulated in the liver, from 0.79 ng/g at four days to 1.38 ng/g at nine days. Although the concentrations of FB found in the muscles was very low, an accumulation of FB1 over time was observed in this tissue, with concentrations of 0.036 and 0.072 ng FB1/g being measured after four and nine days of exposure, respectively. Feeding algo-clay to the chickens reduced the accumulation of FB1 in the liver and muscle by , approximately 40 and 50% on day nine, respectively. By contrast, only a weak non-significant effect was observed on day four. The decrease in the concentration of FB observed in tissues of chickens fed FB plus algo-clay on day nine was accompanied by a decrease in Sa and So contents in the liver compared to the levels of Sa and So measured in chickens fed FB alone. FB1 in the liver and Sa or So contents were correlated in liver tissue, confirming that both FB1 and Sa are suitable biomarkers of FB exposure in chickens. Further studies are necessary to determine whether FB can accumulate at higher levels in chicken tissues with an increase in the time of exposure and in the age of the animals. Full article

(This article belongs to the Special Issue Effects of Mycotoxins on Health and Performance in Animals)

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19 pages, 2389 KiB

Open AccessEditor’s ChoiceArticle

The Influence of OAT1 Density and Functionality on Indoxyl Sulfate Transport in the Human Proximal Tubule: An Integrated Computational and In Vitro Study

by Jasia King, Silvia M. Mihaila, Sabbir Ahmed, Roman Truckenmüller, Stefan Giselbrecht, Rosalinde Masereeuw and Aurélie Carlier

Toxins 2021, 13(10), 674; https://doi.org/10.3390/toxins13100674 - 22 Sep 2021

Cited by 2 | Viewed by 3707

Abstract

Research has shown that traditional dialysis is an insufficient long-term therapy for patients suffering from end-stage kidney disease due to the high retention of uremic toxins in the blood as a result of the absence of the active transport functionality of the proximal [...] Read more.

Research has shown that traditional dialysis is an insufficient long-term therapy for patients suffering from end-stage kidney disease due to the high retention of uremic toxins in the blood as a result of the absence of the active transport functionality of the proximal tubule (PT). The PT’s function is defined by the epithelial membrane transporters, which have an integral role in toxin clearance. However, the intricate PT transporter–toxin interactions are not fully explored, and it is challenging to decouple their effects in toxin removal in vitro. Computational models are necessary to unravel and quantify the toxin–transporter interactions and develop an alternative therapy to dialysis. This includes the bioartificial kidney, where the hollow dialysis fibers are covered with kidney epithelial cells. In this integrated experimental–computational study, we developed a PT computational model that focuses on indoxyl sulfate (IS) transport by organic anionic transporter 1 (OAT1), capturing the transporter density in detail along the basolateral cell membrane as well as the activity of the transporter and the inward boundary flux. The unknown parameter values of the OAT1 density

(1.15 \times 10^{7} transporters µ m^{- 2})

, IS uptake (

1.75 \times 10^{- 5} µ M^{- 1} s^{- 1})

, and dissociation (

4.18 \times 10^{- 4} s^{- 1})

were fitted and validated with experimental LC-MS/MS time-series data of the IS concentration. The computational model was expanded to incorporate albumin conformational changes present in uremic patients. The results suggest that IS removal in the physiological model was influenced mainly by transporter density and IS dissociation rate from OAT1 and not by the initial albumin concentration. While in uremic conditions considering albumin conformational changes, the rate-limiting factors were the transporter density and IS uptake rate, which were followed closely by the albumin-binding rate and IS dissociation rate. In summary, the results of this study provide an exciting avenue to help understand the toxin–transporter complexities in the PT and make better-informed decisions on bioartificial kidney designs and the underlining transporter-related issues in uremic patients. Full article

(This article belongs to the Section Uremic Toxins)

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22 pages, 2774 KiB

Open AccessEditor’s ChoiceArticle

Modelling the Renal Excretion of the Mycotoxin Deoxynivalenol in Humans in an Everyday Situation

by Annick D. van den Brand, Rudolf Hoogenveen, Marcel J. B. Mengelers, Marco Zeilmaker, Gunnar S. Eriksen, Silvio Uhlig, Anne Lise Brantsæter, Hubert A. A. M. Dirven and Trine Husøy

Toxins 2021, 13(10), 675; https://doi.org/10.3390/toxins13100675 - 22 Sep 2021

Cited by 8 | Viewed by 3765

Abstract

The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from [...] Read more.

The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from the EuroMix biomonitoring study, the intake of DON from each meal was calculated and the excretion of DON and its metabolites was analyzed for each urine void collected separately throughout a 24-h period. The relation between DON and DON15GlcA was analyzed with a statistical model to assess the residence time and the excreted fraction of ingested DON as DON15GlcA (f_{abs_excr}). F_{abs_excr} was treated as a random effect variable to address its heterogeneity in the population. The estimated time in which 97.5% of the ingested DON was excreted as DON15GlcA was 12.1 h, the elimination half-life was 4.0 h. Based on the estimated f_{abs_excr}, the mean reversed dosimetry factor (RDF) of DON15GlcA was 2.28. This RDF can be used to calculate the amount of total DON intake in an everyday situation, based on the excreted amount of DON15GlcA. We show that urine samples collected over 24 h are the optimal design to study DON exposure by HBM. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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13 pages, 1302 KiB

Open AccessEditor’s ChoiceArticle

Impact of Phytochemicals on Viability and Cereulide Toxin Synthesis in Bacillus cereus Revealed by a Novel High-Throughput Method, Coupling an AlamarBlue-Based Assay with UPLC-MS/MS

by Markus Kranzler, Elrike Frenzel, Veronika Walser, Thomas F. Hofmann, Timo D. Stark and Monika Ehling-Schulz

Toxins 2021, 13(9), 672; https://doi.org/10.3390/toxins13090672 - 21 Sep 2021

Cited by 3 | Viewed by 4203

Abstract

Due to its food-poisoning potential, Bacillus cereus has attracted the attention of the food industry. The cereulide-toxin-producing subgroup is of particular concern, as cereulide toxin is implicated in broadscale food-borne outbreaks and occasionally causes fatalities. The health risks associated with long-term cereulide exposure [...] Read more.

Due to its food-poisoning potential, Bacillus cereus has attracted the attention of the food industry. The cereulide-toxin-producing subgroup is of particular concern, as cereulide toxin is implicated in broadscale food-borne outbreaks and occasionally causes fatalities. The health risks associated with long-term cereulide exposure at low doses remain largely unexplored. Natural substances, such as plant-based secondary metabolites, are widely known for their effective antibacterial potential, which makes them promising as ingredients in food and also as a surrogate for antibiotics. In this work, we tested a range of structurally related phytochemicals, including benzene derivatives, monoterpenes, hydroxycinnamic acid derivatives and vitamins, for their inhibitory effects on the growth of B. cereus and the production of cereulide toxin. For this purpose, we developed a high-throughput, small-scale method which allowed us to analyze B. cereus survival and cereulide production simultaneously in one workflow by coupling an AlamarBlue-based viability assay with ultraperformance liquid chromatography–mass spectrometry (UPLC-MS/MS). This combinatory method allowed us to identify not only phytochemicals with high antibacterial potential, but also ones specifically eradicating cereulide biosynthesis already at very low concentrations, such as gingerol and curcumin. Full article

(This article belongs to the Special Issue Foodborne Intoxications and Toxicoinfections—Major Pathogens and Challenges)

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16 pages, 2350 KiB

Open AccessEditor’s ChoiceArticle

Removal of Aflatoxin B₁ by Edible Mushroom-Forming Fungi and Its Mechanism

by Min-Jung Choo, Sung-Yong Hong, Soo-Hyun Chung and Ae-Son Om

Toxins 2021, 13(9), 668; https://doi.org/10.3390/toxins13090668 - 18 Sep 2021

Cited by 10 | Viewed by 4476

Abstract

Aflatoxins (AFs) are biologically active toxic metabolites, which are produced by certain toxigenic Aspergillus sp. on agricultural crops. In this study, five edible mushroom-forming fungi were analyzed using high-performance liquid chromatography fluorescence detector (HPLC-FLD) for their ability to remove aflatoxin B₁ (AFB [...] Read more.

Aflatoxins (AFs) are biologically active toxic metabolites, which are produced by certain toxigenic Aspergillus sp. on agricultural crops. In this study, five edible mushroom-forming fungi were analyzed using high-performance liquid chromatography fluorescence detector (HPLC-FLD) for their ability to remove aflatoxin B₁ (AFB₁), one of the most potent naturally occurring carcinogens known. Bjerkandera adusta and Auricularia auricular-judae showed the most significant AFB₁ removal activities (96.3% and 100%, respectively) among five strains after 14-day incubation. The cell lysate from B. adusta exhibited higher AFB₁ removal activity (35%) than the cell-free supernatant (13%) after 1-day incubation and the highest removal activity (80%) after 5-day incubation at 40 °C. In addition, AFB₁ analyses using whole cells, cell lysates, and cell debris from B. adusta showed that cell debris had the highest AFB₁ removal activity at 5th day (95%). Moreover, exopolysaccharides from B. adusta showed an increasing trend (24–48%) similar to whole cells and cell lysates after 5- day incubation. Our results strongly suggest that AFB₁ removal activity by whole cells was mainly due to AFB₁ binding onto cell debris during early incubation and partly due to binding onto cell lysates along with exopolysaccharides after saturation of AFB₁ binding process onto cell wall components. Full article

(This article belongs to the Special Issue Determination and Detoxification Strategies of Mycotoxins)

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14 pages, 1984 KiB

Open AccessEditor’s ChoiceArticle

Naturally Occurring Fusarium Species and Mycotoxins in Oat Grains from Manitoba, Canada

by M. Nazrul Islam, Mourita Tabassum, Mitali Banik, Fouad Daayf, W. G. Dilantha Fernando, Linda J. Harris, Srinivas Sura and Xiben Wang

Toxins 2021, 13(9), 670; https://doi.org/10.3390/toxins13090670 - 18 Sep 2021

Cited by 19 | Viewed by 5623

Abstract

Fusarium head blight (FHB) can lead to dramatic yield losses and mycotoxin contamination in small grain cereals in Canada. To assess the extent and severity of FHB in oat, samples collected from 168 commercial oat fields in the province of Manitoba, Canada, during [...] Read more.

Fusarium head blight (FHB) can lead to dramatic yield losses and mycotoxin contamination in small grain cereals in Canada. To assess the extent and severity of FHB in oat, samples collected from 168 commercial oat fields in the province of Manitoba, Canada, during 2016–2018 were analyzed for the occurrence of Fusarium head blight and associated mycotoxins. Through morphological and molecular analysis, F. poae was found to be the predominant Fusarium species affecting oat, followed by F. graminearum, F. sporotrichioides, F. avenaceum, and F. culmorum. Deoxynivalenol (DON) and nivalenol (NIV), type B trichothecenes, were the two most abundant Fusarium mycotoxins detected in oat. Beauvericin (BEA) was also frequently detected, though at lower concentrations. Close clustering of F. poae and NIV/BEA, F. graminearum and DON, and F. sporotrichioides and HT2/T2 (type A trichothecenes) was detected in the principal component analysis. Sampling location and crop rotation significantly impacted the concentrations of Fusarium mycotoxins in oat. A phylogenetic analysis of 95 F. poae strains from Manitoba was conducted using the concatenated nucleotide sequences of Tef-1α, Tri1, and Tri8 genes. The results indicated that all F. poae strains belong to a monophyletic lineage. Four subgroups of F. poae strains were identified; however, no correlations were observed between the grouping of F. poae strains and sample locations/crop rotations. Full article

(This article belongs to the Special Issue Selected Papers from the 15th European Fusarium Seminar)

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