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Toxins, Volume 12, Issue 7 (July 2020) – 21 articles

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Open AccessArticle
Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A Against Clinical Isolates of Antibiotic-Resistant Bacteria
Toxins 2020, 12(7), 444; https://doi.org/10.3390/toxins12070444 (registering DOI) - 08 Jul 2020
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Abstract
Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution [...] Read more.
Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties. Full article
(This article belongs to the Special Issue Microbial and Plant Phytotoxins)
Open AccessArticle
Detection of Chaetomium globosum, Ch. cochliodes and Ch. rectangulare during the Diversity Tracking of Mycotoxin-Producing Chaetomium-Like Isolates Obtained in Buildings in Finland
Toxins 2020, 12(7), 443; https://doi.org/10.3390/toxins12070443 (registering DOI) - 08 Jul 2020
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Abstract
The diversity of Chaetomium-like isolates in buildings in Finland is poorly documented. This paper describes a set of methods for rapid diversity tracking of 42 indoor Chaetomium-like isolates. These isolates were categorized based on their fluorescence emission, ascomatal hair morphology, responses [...] Read more.
The diversity of Chaetomium-like isolates in buildings in Finland is poorly documented. This paper describes a set of methods for rapid diversity tracking of 42 indoor Chaetomium-like isolates. These isolates were categorized based on their fluorescence emission, ascomatal hair morphology, responses in three bioassays and resistance/sensitivity to the wetting agent Genapol X-080. Thirty-nine toxigenic isolates were identified [Ch. globosum (n = 35), Ch. cochliodes (n = 2) and Ch. rectangulare (n = 2)]. These isolates were identified down to the species level by tef1α gene sequencing. The major toxic substances in the ethanol extracts of the Ch. globosum and Ch. cochliodes strains were chaetoglobosin, chaetoviridin A and C, chaetomugilin D and chaetomin, identified based on HPLC-UV and mass spectrometry data (MS and MS/MS). Ethanol extracts from pure Ch. globosum cultures exhibited a toxicological profile in the boar sperm motility inhibition assay (BSMI), sperm membrane integrity damage assay (SMID) and inhibition of cell proliferation (ICP) assay, similar to that exhibited by pure chaetoglobosin A. Overall, differences in fluorescence, morphology, toxicity profile, mycotoxin production and sensitivity to chemicals were consistent with those in tef1α sequencing results for species identification. The results indicate the presence of Ch. cochliodes and Ch. rectangulare in Finnish buildings, representing a new finding. Full article
(This article belongs to the Section Mycotoxins)
Open AccessArticle
Change in Paralytic Shellfish Toxins in the Mussel Mytilus galloprovincialis Depending on Dynamics of Harmful Alexandrium catenella (Group I) in the Geoje Coast (South Korea) during Bloom Season
Toxins 2020, 12(7), 442; https://doi.org/10.3390/toxins12070442 - 07 Jul 2020
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Abstract
Paralytic shellfish toxins (PSTs) produced by Alexandrium catenella (formerly A. tamarense) in Korean coastal waters caused the deaths of four people (in 1986 and 1996) who consumed contaminated mussels (Mytilus edulis). This led to more detailed consideration of the risks [...] Read more.
Paralytic shellfish toxins (PSTs) produced by Alexandrium catenella (formerly A. tamarense) in Korean coastal waters caused the deaths of four people (in 1986 and 1996) who consumed contaminated mussels (Mytilus edulis). This led to more detailed consideration of the risks of PST outbreaks and incidents in Korea, including the introduction of shellfish collection bans. In this study, we investigated the relationships between A. catenella population dynamics and PST accumulation in the mussel M. galloprovincialis. Discharges from the Nakdong River affect the environmental conditions along the Geoje coast, resulting in low salinity and high nutrient levels that trigger blooms of A. catenella. At the toxin peak on 24 April 2017, the toxins detected in A. catenella cells were C1, gonyautoxin (GTX)1 and GTX2, whereas the concentrations of PSTs in M. galloprovincialis were high and in the order of GTX4 > GTX1 > GTX3 > saxitoxin (STX) > GTX2 > neoSTX > decarbamoylgonyautoxin (dcGTX)2 > dc GTX3. The PST level in mussels was also high. At 15 °C, the PSTs are constantly found to be higher (10-fold higher in 2017 and 30-fold higher in 2018) than safe levels for human consumption (80 μg STX diHCl equivalents 100 g−1). Full article
(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)
Open AccessArticle
Spread of Jacobaea vulgaris and Occurrence of Pyrrolizidine Alkaloids in Regionally Produced Honeys from Northern Germany: Inter- and Intra-Site Variations and Risk Assessment for Special Consumer Groups
Toxins 2020, 12(7), 441; https://doi.org/10.3390/toxins12070441 - 07 Jul 2020
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Abstract
Pyrrolizidine alkaloids (PA) and PA N-oxides (PANO) are secondary plant metabolites exhibiting genotoxic and carcinogenic properties. Apart from the roots and leaves, PA/PANO are particularly present in pollen and nectar. Therefore, the spread of Jacobaea vulgaris in certain regions of northern Germany [...] Read more.
Pyrrolizidine alkaloids (PA) and PA N-oxides (PANO) are secondary plant metabolites exhibiting genotoxic and carcinogenic properties. Apart from the roots and leaves, PA/PANO are particularly present in pollen and nectar. Therefore, the spread of Jacobaea vulgaris in certain regions of northern Germany has an impact on the safety of honey produced in that region. In this study, raw honey samples (n = 437) were collected from usually three individual beehives per site (n = 73) in the district of Ostholstein and analyzed for 25 PA/PANO. The results reveal mean levels of 8.4, 1.5, and 72.6 µg/kg and maximum levels of 111, 59.4, and 3313 µg/kg, depending on the season (summer 2015 and spring/summer 2016, respectively). As far as individual data are concerned, sites near areas with J. vulgaris growth did not necessarily result in high PA/PANO values. Furthermore, intra-site investigations revealed remarkable differences in PA/PANO levels of raw honey collected by different bee colonies at the same site. Consumption of these regionally produced honeys entails an increased exposure to PA/PANO, especially in children and high consumers. Margin of exposure values of <10,000 and an exceedance of the health-based guidance value highlight that regionally produced and marketed honey must be considered with care for a proper risk assessment and risk management. Full article
(This article belongs to the Section Plant Toxins)
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Open AccessReview
Over 25 Years of Pediatric Botulinum Toxin Treatments: What Have We Learned from Injection Techniques, Doses, Dilutions, and Recovery of Repeated Injections?
Toxins 2020, 12(7), 440; https://doi.org/10.3390/toxins12070440 - 06 Jul 2020
Viewed by 148
Abstract
Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction [...] Read more.
Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction of spastic equinus gait in children with cerebral palsy. The upper limb injection goals include improvements in function, better positioning of the arm, and facilitating the ease of care. Neurotoxin type A is the most widely used serotype in the pediatric population. After being injected into muscle, the release of acetylcholine at cholinergic nerve endings is blocked, and a temporary denervation and atrophy ensues. Targeting the correct muscle close to the neuromuscular junctions is considered essential and localization techniques have developed over time. However, each technique has its own limitations. The role of BTXA is flexible, but limited by the temporary mode of action as a focal spasticity treatment and the restrictions on the total dose deliverable per visit. As a mode of treatment, repeated BTXA injections are needed. This literature reviewed BTXA injection techniques, doses and dilutions, the recovery of muscles and the impact of repeated injections, with a focus on the pediatric population. Suggestions for future studies are also discussed. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
Open AccessReview
Immune Dysfunction in Uremia 2020
Toxins 2020, 12(7), 439; https://doi.org/10.3390/toxins12070439 - 05 Jul 2020
Viewed by 224
Abstract
Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. [...] Read more.
Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties. Full article
(This article belongs to the Special Issue Immune Dysfunction in Uremia)
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Open AccessArticle
Structural and Functional Insights into the C-terminal Fragment of Insecticidal Vip3A Toxin of Bacillus thuringiensis
Toxins 2020, 12(7), 438; https://doi.org/10.3390/toxins12070438 - 05 Jul 2020
Viewed by 202
Abstract
The vegetative insecticidal proteins (Vips) secreted by Bacillus thuringiensis are regarded as the new generation of insecticidal toxins because they have different insecticidal properties compared with commonly applied insecticidal crystal proteins (Cry toxins). Vip3A toxin, representing the vast majority of Vips, has been [...] Read more.
The vegetative insecticidal proteins (Vips) secreted by Bacillus thuringiensis are regarded as the new generation of insecticidal toxins because they have different insecticidal properties compared with commonly applied insecticidal crystal proteins (Cry toxins). Vip3A toxin, representing the vast majority of Vips, has been used commercially in transgenic crops and bio-insecticides. However, the lack of both structural information on Vip3A and a clear understanding of its insecticidal mechanism at the molecular level limits its further development and broader application. Here we present the first crystal structure of the C-terminal fragment of Vip3A toxin (Vip3Aa11200–789). Since all members of this insecticidal protein family are highly conserved, the structure of Vip3A provides unique insight into the general domain architecture and protein fold of the Vip3A family of insecticidal toxins. Our structural analysis reveals a four-domain organization, featuring a potential membrane insertion region, a receptor binding domain, and two potential glycan binding domains of Vip3A. In addition, cytotoxicity assays and insect bioassays show that the purified C-terminal fragment of Vip3Aa toxin alone have no insecticidal activity. Taken together, these findings provide insights into the mode of action of the Vip3A family of insecticidal toxins and will boost the development of Vip3A into more efficient bio-insecticides. Full article
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Open AccessArticle
Quantitative Measurement of Melittin in Asian Honeybee Venom Using a New Method Including UPLC-QqTOF-MS
Toxins 2020, 12(7), 437; https://doi.org/10.3390/toxins12070437 - 04 Jul 2020
Viewed by 183
Abstract
Asian honeybee venom is widely used in traditional oriental medicine. Melittin is the main component of Asian honeybee venom. In the present study, an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) method was used for accurate qualitative and quantitative analyses of melittin in [...] Read more.
Asian honeybee venom is widely used in traditional oriental medicine. Melittin is the main component of Asian honeybee venom. In the present study, an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) method was used for accurate qualitative and quantitative analyses of melittin in Asian honeybee venom. The results showed that the dynamic linear range of melittin was from 0.094 to 20 μg/mL, and the limit of quantification was 0.3125 μg/mL. The spiking recovery of melittin in honeybee venom ranged from 84.88% to 93.05%. Eighteen Asian honeybee venom samples in eighteen batches were collected from two different zones of China, and their melittin contents were measured. The contents of melittin in Asian honeybee venom samples was 33.9–46.23% of dry weight. This method proved a useful tool for the rapid evaluation of the authenticity and quality of Asian honeybee venom in terms of the melittin contents, and will contribute to a broader understanding of Asian honeybee venom. Full article
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Open AccessArticle
Co-Occurrence of Tetrodotoxin and Saxitoxins and Their Intra-Body Distribution in the Pufferfish Canthigaster valentini
Toxins 2020, 12(7), 436; https://doi.org/10.3390/toxins12070436 - 03 Jul 2020
Viewed by 238
Abstract
Pufferfish of the family Tetraodontidae possess tetrodotoxin (TTX) and/or saxitoxins (STXs), but the toxin ratio differs, depending on the genus or species. In the present study, to clarify the distribution profile of TTX and STXs in Tetraodontidae, we investigated the composition and intra-body [...] Read more.
Pufferfish of the family Tetraodontidae possess tetrodotoxin (TTX) and/or saxitoxins (STXs), but the toxin ratio differs, depending on the genus or species. In the present study, to clarify the distribution profile of TTX and STXs in Tetraodontidae, we investigated the composition and intra-body distribution of the toxins in Canthigaster valentini. C. valentini specimens (four male and six female) were collected from Amami-Oshima Island, Kagoshima Prefecture, Japan, and the toxins were extracted from the muscle, liver, intestine, gallbladder, gonads, and skin. Analysis of the extracts for TTX by liquid chromatography tandem mass spectrometry and of STXs by high-performance liquid chromatography with post-column fluorescence derivatization revealed TTX, as well as a large amount of STXs, with neoSTX as the main component and dicarbamoylSTX and STX itself as minor components, in the skin and ovary. The toxins were also detected in the other tissues, but in much lower amounts than in the skin and ovary. The TTX/STX ratio varied greatly, depending on the tissue, but TTX was the major toxin component in the whole body, and STXs accounted for 25% and 13% of the total toxin amount in males and females, respectively. Like the marine pufferfish of the genus Arothron, C. valentini should be considered a pufferfish with considerable amounts of both TTX and STXs present simultaneously. Full article
(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)
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Open AccessArticle
Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium
Toxins 2020, 12(7), 435; https://doi.org/10.3390/toxins12070435 - 03 Jul 2020
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Abstract
Hemolytic uremic syndrome (HUS) is a severe renal disease that is often preceded by infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). The exact mechanism of Stx-mediated inflammation on human glomerular microvascular endothelial cells (HGMVECs) during HUS is still not well understood. In [...] Read more.
Hemolytic uremic syndrome (HUS) is a severe renal disease that is often preceded by infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). The exact mechanism of Stx-mediated inflammation on human glomerular microvascular endothelial cells (HGMVECs) during HUS is still not well understood. In this study, we investigated the effect of Stx1 on the gene expression of proteins involved in leucocyte-mediated and complement-mediated inflammation. Our results showed that Stx1 enhances the mRNA and protein expression of heparan sulfate proteoglycan (HSPG) syndecan-4 in HGMVECs pre-stimulated with tumor necrosis factor α (TNFα). CD44 was upregulated on mRNA but not on protein level; no effect on the mRNA expression of other tested HSPGs glypican-1 and betaglycan was observed. Furthermore, Stx1 upregulated the mRNA, cell surface expression, and supernatant levels of the intercellular adhesion molecule-1 (ICAM-1) in HGMVECs. Interestingly, no effect on the protein levels of alternative pathway (AP) components was observed, although C3 mRNA was upregulated. All observed effects were much stronger in HGMVECs than in human umbilical endothelial cells (HUVECs), a common model cell type used in endothelial studies. Our results provide new insights into the role of Stx1 in the pathogenesis of HUS. Possibilities to target the overexpression of syndecan-4 and ICAM-1 for STEC-HUS therapy should be investigated in future studies. Full article
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Open AccessReview
Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System
Toxins 2020, 12(7), 434; https://doi.org/10.3390/toxins12070434 - 02 Jul 2020
Viewed by 185
Abstract
Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridium botulinum, the causing agent for botulism, in different serotypes, seven of which (A–G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking [...] Read more.
Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridium botulinum, the causing agent for botulism, in different serotypes, seven of which (A–G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking SNARE (soluble N-ethylmale-imide-sensitive factor-attachment protein receptors) complex formation and vesicle release from the neuronal terminal through the specific cleavage of SNARE proteins. The action of BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field has set the foundation for the use of these toxins in a variety of human pathologies characterized by excessive muscle contractions. In parallel, BoNTs became a cosmetic drug due to its power to ward off facial wrinkles following the activity of the mimic muscles. Successively, BoNTs became therapeutic agents that have proven to be successful in the treatment of different neurological disorders, with new indications emerging or being approved each year. In particular, BoNT/A became the treatment of excellence not only for muscle hyperactivity conditions, such as dystonia and spasticity, but also to reduce pain in a series of painful states, such as neuropathic pain, lumbar and myofascial pain, and to treat various dysfunctions of the urinary bladder. This review summarizes recent experimental findings on the potential efficacy of BoNTs in favoring nerve regeneration after traumatic injury in the peripheral nervous system, such as the injury of peripheral nerves, like sciatic nerve, and in the central nervous system, such as spinal cord injury. Full article
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Open AccessArticle
Low Doses of Mycotoxin Mixtures below EU Regulatory Limits Can Negatively Affect the Performance of Broiler Chickens: A Longitudinal Study
Toxins 2020, 12(7), 433; https://doi.org/10.3390/toxins12070433 - 01 Jul 2020
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Abstract
Several studies have reported a wide range of severe health effects as well as clinical signs, when livestock animals are exposed to high concentration of mycotoxins. However, little is known regarding health effects of mycotoxins at low levels. Thus, a long-term feeding trial [...] Read more.
Several studies have reported a wide range of severe health effects as well as clinical signs, when livestock animals are exposed to high concentration of mycotoxins. However, little is known regarding health effects of mycotoxins at low levels. Thus, a long-term feeding trial (between May 2017 and December 2019) was used to evaluate the effect of low doses of mycotoxin mixtures on performance of broiler chickens fed a naturally contaminated diet. In total, 18 successive broiler performance trials were carried out during the study period, with approximately 2200 one-day-old Ross-308 chicks used for each trial. Feed samples given to birds were collected at the beginning of each trial and analysed for multi-mycotoxins using a validated LC-MS/MS method. Furthermore, parameters including feed intake, body weight and feed efficiency were recorded on a weekly basis. In total, 24 mycotoxins were detected in samples analysed with deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FBs), apicidin, enniatins (ENNs), emodin and beauvericin (BEV), the most prevalent mycotoxins. Furthermore, significantly higher levels (however below EU guidance values) of DON, ZEN, FBs, BEV, ENNs and diacetoxyscirpenol (DAS) were detected in 6 of the 18 performance trials. A strong positive relationship was observed between broilers feed efficiency and DON (R2 = 0.85), FBs (R2 = 0.53), DAS (R2 = 0.86), ZEN (R2 = 0.92), ENNs (R2 = 0.60) and BEV (R2 = 0.73). Moreover, a three-way interaction regression model revealed that mixtures of ZEN, DON and FBs (p = 0.01, R2 = 0.84) and ZEN, DON and DAS (p = 0.001, R2 = 0.91) had a statistically significant interaction effect on the birds’ feed efficiency. As farm animals are often exposed to low doses of mycotoxin mixtures (especially fusarium mycotoxins), a cumulative risk assessment in terms of measuring and mitigating against the economic, welfare and health impacts is needed for this group of compounds. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessArticle
Potential of Bacteriocins from Lactobacillus taiwanensis for Producing Bacterial Ghosts as a Next Generation Vaccine
Toxins 2020, 12(7), 432; https://doi.org/10.3390/toxins12070432 - 01 Jul 2020
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Abstract
Bacteriocins are functionally diverse toxins produced by most microbes and are potent antimicrobial peptides (AMPs) for bacterial ghosts as next generation vaccines. Here, we first report that the AMPs secreted from Lactobacillus taiwanensis effectively form ghosts of pathogenic bacteria and are identified as [...] Read more.
Bacteriocins are functionally diverse toxins produced by most microbes and are potent antimicrobial peptides (AMPs) for bacterial ghosts as next generation vaccines. Here, we first report that the AMPs secreted from Lactobacillus taiwanensis effectively form ghosts of pathogenic bacteria and are identified as diverse bacteriocins, including novel ones. In detail, a cell-free supernatant from L. taiwanensis exhibited antimicrobial activities against pathogenic bacteria and was observed to effectively cause cellular lysis through pore formation in the bacterial membrane using scanning electron microscopy (SEM). The treatment of the cell-free supernatant with proteinase K or EDTA proved that the antimicrobial activity is mediated by AMPs, and the purification of AMPs using Sep-Pak columns indicated that the cell-free supernatant includes various amphipathic peptides responsible for the antimicrobial activity. Furthermore, the whole-genome sequencing of L. taiwanensis revealed that the strain has diverse bacteriocins, confirmed experimentally to function as AMPs, and among them are three novel bacteriocins, designated as Tan 1, Tan 2, and Tan 3. We also confirmed, using SEM, that Tan 2 effectively produces bacterial ghosts. Therefore, our data suggest that the bacteriocins from L. taiwanensis are potentially useful as a critical component for the preparation of bacterial ghosts. Full article
(This article belongs to the Special Issue Drug Development Using Natural Toxins)
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Open AccessReview
Genomics of Maize Resistance to Fusarium Ear Rot and Fumonisin Contamination
Toxins 2020, 12(7), 431; https://doi.org/10.3390/toxins12070431 - 30 Jun 2020
Viewed by 222
Abstract
Food contamination with mycotoxins is a worldwide concern, because these toxins produced by several fungal species have detrimental effects on animal and/or human health. In maize, fumonisins are among the toxins with the highest threatening potential because they are mainly produced by Fusarium [...] Read more.
Food contamination with mycotoxins is a worldwide concern, because these toxins produced by several fungal species have detrimental effects on animal and/or human health. In maize, fumonisins are among the toxins with the highest threatening potential because they are mainly produced by Fusarium verticillioides, which is distributed worldwide. Plant breeding has emerged as an effective and environmentally safe method to reduce fumonisin levels in maize kernels, but although phenotypic selection has proved effective for improving resistance to fumonisin contamination, further resources should be mobilized to meet farmers’ needs. Selection based on molecular markers linked to quantitative trait loci (QTL) for resistance to fumonisin contamination or/and genotype values obtained using prediction models with markers distributed across the whole genome could speed up breeding progress. Therefore, in the current paper, previously identified genomic regions, genes, and/or pathways implicated in resistance to fumonisin accumulation will be reviewed. Studies done until now have provide many markers to be used by breeders, but to get further insight on plant mechanisms to defend against fungal infection and to limit fumonisin contamination, the genes behind those QTLs should be identified. Full article
(This article belongs to the Special Issue Foodborne Toxin Detection and Prevention Research)
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Open AccessReview
Insecticidal Activity of Bacillus thuringiensis Proteins Against Coleopteran Pests
Toxins 2020, 12(7), 430; https://doi.org/10.3390/toxins12070430 - 29 Jun 2020
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Abstract
Bacillus thuringiensis is the most successful microbial insecticide agent and its proteins have been studied for many years due to its toxicity against insects mainly belonging to the orders Lepidoptera, Diptera and Coleoptera, which are pests of agro-forestry and medical-veterinary interest. However, studies [...] Read more.
Bacillus thuringiensis is the most successful microbial insecticide agent and its proteins have been studied for many years due to its toxicity against insects mainly belonging to the orders Lepidoptera, Diptera and Coleoptera, which are pests of agro-forestry and medical-veterinary interest. However, studies on the interactions between this bacterium and the insect species classified in the order Coleoptera are more limited when compared to other insect orders. To date, 45 Cry proteins, 2 Cyt proteins, 11 Vip proteins, and 2 Sip proteins have been reported with activity against coleopteran species. A number of these proteins have been successfully used in some insecticidal formulations and in the construction of transgenic crops to provide protection against main beetle pests. In this review, we provide an update on the activity of Bt toxins against coleopteran insects, as well as specific information about the structure and mode of action of coleopteran Bt proteins. Full article
Open AccessArticle
Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach
Toxins 2020, 12(7), 429; https://doi.org/10.3390/toxins12070429 - 29 Jun 2020
Viewed by 271
Abstract
Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, [...] Read more.
Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species. Full article
(This article belongs to the Special Issue Mycotoxins and Its Gene Regulation)
Open AccessArticle
The Efficacy of Hydrogen Peroxide in Mitigating Cyanobacterial Blooms and Altering Microbial Communities across Four Lakes in NY, USA
Toxins 2020, 12(7), 428; https://doi.org/10.3390/toxins12070428 - 29 Jun 2020
Viewed by 246
Abstract
Hydrogen peroxide (H2O2) has been proposed as an agent to mitigate toxic cyanobacterial blooms due to the heightened sensitivity of cyanobacteria to reactive oxygen species relative to eukaryotic organisms. Here, experiments were conducted using water from four diverse, eutrophic [...] Read more.
Hydrogen peroxide (H2O2) has been proposed as an agent to mitigate toxic cyanobacterial blooms due to the heightened sensitivity of cyanobacteria to reactive oxygen species relative to eukaryotic organisms. Here, experiments were conducted using water from four diverse, eutrophic lake ecosystems to study the effects of H2O2 on cyanobacteria and non-target members of the microbial community. H2O2 was administered at 4 µg L−1 and a combination of fluorometry, microscopy, flow cytometry, and high throughput DNA sequencing were used to quantify the effects on eukaryotic and prokaryotic plankton communities. The addition of H2O2 resulted in a significant reduction in cyanobacteria levels in nearly all experiments (10 of 11), reducing their relative abundance from, on average, 85% to 29% of the total phytoplankton community with Planktothrix being highly sensitive, Microcystis being moderately sensitive, and Cylindrospermopsis being most resistant. Concurrently, eukaryotic algal levels increased in 75% of experiments. The bacterial phyla Actinobacteria, cyanobacteria, Planctomycetes, and Verrucomicrobia were most negatively impacted by H2O2, with Actinobacteria being the most sensitive. The ability of H2O2 to reduce, but not fully eliminate, cyanobacteria from the eutrophic water bodies studied here suggests it may not be an ideal mitigation approach in high biomass ecosystems. Full article
(This article belongs to the Special Issue Removal of Cyanobacteria and Cyanotoxins in Waters)
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Open AccessArticle
Novel Ergot Alkaloids Production from Penicillium citrinum Employing Response Surface Methodology Technique
Toxins 2020, 12(7), 427; https://doi.org/10.3390/toxins12070427 - 29 Jun 2020
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Abstract
Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species Penicillium citrinum. To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of [...] Read more.
Ergot alkaloids are novel pharmaceutical and therapeutic agents synthesized in this study using fungal species Penicillium citrinum. To get the maximum yield of ergot alkaloids a statistical process of response surface methodology was employed using surface culture fermentation technique. Initially, the strain of Penicillium was improved using physical (ultraviolet (UV) and chemical (ethyl methane sulfonate (EMS) treatments to get the maximum yield of ergot alkaloids through surface culture fermentation technique. After improving the strain, survival rate of colonies of Penicillium citrinum treated with UV and EMS was observed. Only 2.04% living colonies were observed after 150 min of exposure of Penicillium citrinum in UV light and 3.2% living colonies were observed after 20 min of the exposure in EMS. The mutated strains of Penicillium citrinum were screened for their production of ergot alkaloids and after fermentation experiments, maximum yield was obtained from PCUV-4 and PCEMS-1 strains. After strain improvement, Plackett–Burman design (PBD) and Box–Behnken design (BBD) of RSM were employed and 10-fold yield enhancement (35.60 mg/100 mL) of ergot alkaloids was achieved. This enhancement in yield of ergot alkaloids proved the positive impacts of RSM and UV on the yield of ergot alkaloids. The study provides a cost effective, economical and sustainable process to produce medically important ergot alkaloids which can be used in various pharmaceutical formulations to treat human diseases. Full article
(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)
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Open AccessArticle
Improved Antithrombotic Activity and Diminished Bleeding Side Effect of a PEGylated αIIbβ3 Antagonist, Disintegrin
Toxins 2020, 12(7), 426; https://doi.org/10.3390/toxins12070426 - 28 Jun 2020
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Abstract
Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decrease degradation and reduces renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety and pharmacokinetic profiles [...] Read more.
Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decrease degradation and reduces renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety and pharmacokinetic profiles and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, there was no effect of PEG-RR in human whole blood coagulation even given at a higher concentration (30 μg/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in FcγRIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases. Full article
(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)
Open AccessArticle
Molecular Mechanism by Which Cobra Venom Cardiotoxins Interact with the Outer Mitochondrial Membrane
Toxins 2020, 12(7), 425; https://doi.org/10.3390/toxins12070425 (registering DOI) - 27 Jun 2020
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Abstract
Cardiotoxin CTII from Naja oxiana cobra venom translocates to the intermembrane space (IMS) of mitochondria to disrupt the structure and function of the inner mitochondrial membrane. At low concentrations, CTII facilitates ATP-synthase activity, presumably via the formation of non-bilayer, immobilized phospholipids that are [...] Read more.
Cardiotoxin CTII from Naja oxiana cobra venom translocates to the intermembrane space (IMS) of mitochondria to disrupt the structure and function of the inner mitochondrial membrane. At low concentrations, CTII facilitates ATP-synthase activity, presumably via the formation of non-bilayer, immobilized phospholipids that are critical in modulating ATP-synthase activity. In this study, we investigated the effects of another cardiotoxin CTI from Naja oxiana cobra venom on the structure of mitochondrial membranes and on mitochondrial-derived ATP synthesis. By employing robust biophysical methods including 31P-NMR and 1H-NMR spectroscopy, we analyzed the effects of CTI and CTII on phospholipid packing and dynamics in model phosphatidylcholine (PC) membranes enriched with 2.5 and 5.0 mol% of cardiolipin (CL), a phospholipid composition that mimics that in the outer mitochondrial membrane (OMM). These experiments revealed that CTII converted a higher percentage of bilayer phospholipids to a non-bilayer and immobilized state and both cardiotoxins utilized CL and PC molecules to form non-bilayer structures. Furthermore, in order to gain further understanding on how cardiotoxins bind to mitochondrial membranes, we employed molecular dynamics (MD) and molecular docking simulations to investigate the molecular mechanisms by which CTII and CTI interactively bind with an in silico phospholipid membrane that models the composition similar to the OMM. In brief, MD studies suggest that CTII utilized the N-terminal region to embed the phospholipid bilayer more avidly in a horizontal orientation with respect to the lipid bilayer and thereby penetrate at a faster rate compared with CTI. Molecular dynamics along with the Autodock studies identified critical amino acid residues on the molecular surfaces of CTII and CTI that facilitated the long-range and short-range interactions of cardiotoxins with CL and PC. Based on our compiled data and our published findings, we provide a conceptual model that explains a molecular mechanism by which snake venom cardiotoxins, including CTI and CTII, interact with mitochondrial membranes to alter the mitochondrial membrane structure to either upregulate ATP-synthase activity or disrupt mitochondrial function. Full article
(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)
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Open AccessArticle
Reducing Ochratoxin A Content in Grape Pomace by Different Methods
Toxins 2020, 12(7), 424; https://doi.org/10.3390/toxins12070424 - 27 Jun 2020
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Abstract
Grape pomace (GP) is the residue of grapes after wine making and is a valuable source of dietary polyphenol and fiber for health promotion. However, studies found the presence of ochratoxin A (OTA) in GP at very high concentrations, which raises a safety [...] Read more.
Grape pomace (GP) is the residue of grapes after wine making and is a valuable source of dietary polyphenol and fiber for health promotion. However, studies found the presence of ochratoxin A (OTA) in GP at very high concentrations, which raises a safety issue in the value-added utilization of GP. This study evaluated the effects of thermal pressure, baking, acid and enzymatic treatments on OTA content in GP. Thermal pressure treatment was conducted with wet GP at 121 °C for 10–30 min in an autoclave; acid treatments were conducted with hydrochloric acid, acetic acid, citric acid, and lactic acid, respectively, at 50 °C for 24 h. Baking was conducted using a cookie model. For enzymatic treatment, purified OTA solution was treated with carboxypeptidase A, alcalase, flavourzyme, pepsin, and lipase, respectively, and the effective enzymes were selected to treat GP. Results show that autoclaving for 10–30 min reduced 19–80% of OTA, varying with treatment time and GP variety. The effectiveness of acid treatment was similar to that of autoclaving and varied with acid type and GP variety. Baking increased the detectable OTA. Among all tested enzymes, carboxypeptidase A was the most effective in reducing OTA, followed by lipase and flavourzyme, but their effects were significantly lower in GP samples. Full article
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