Toxins

25 pages, 4591 KiB

Open AccessArticle

The Parotoid Gland Secretion from Peruvian Toad Rhinella horribilis (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells

by Guillermo Schmeda-Hirschmann, Jean Paulo de Andrade, Marilú Roxana Soto-Vasquez, Paul Alan Arkin Alvarado-García, Charlotte Palominos, Sebastián Fuentes-Retamal, Mathias Mellado, Pablo Correa and Félix A. Urra

Toxins 2020, 12(9), 608; https://doi.org/10.3390/toxins12090608 - 22 Sep 2020

Cited by 10 | Viewed by 4960

Abstract

Since Rhinella sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the Rhinella horribilis toad was confused with the invasive toad Rhinella marina, a species documented with [...] Read more.

Since Rhinella sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the Rhinella horribilis toad was confused with the invasive toad Rhinella marina, a species documented with extensive toxinological studies. In contrast, the chemical composition and biological effects of the parotoid gland secretions (PGS) remain still unknown for R. horribilis. In this work, we determine for the first time 55 compounds from the PGS of R. horribilis, which were identified using HPLC-MS/MS. The crude extract inhibited the proliferation of A549 cancer cells with IC₅₀ values of 0.031 ± 0.007 and 0.015 ± 0.001 µg/mL at 24 and 48 h of exposure, respectively. Moreover, it inhibited the clonogenic capacity, increased ROS levels, and prevented the etoposide-induced apoptosis, suggesting that the effect of R. horribilis poison secretion was by cell cycle blocking before of G2/M-phase checkpoint. Fraction B was the most active and strongly inhibited cancer cell migration. Our results indicate that the PGS of R. horribilis are composed of alkaloids, bufadienolides, and argininyl diacids derivatives, inhibiting the proliferation and migration of A549 cells. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)

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37 pages, 1640 KiB

Open AccessReview

The Role of Escherichia coli Shiga Toxins in STEC Colonization of Cattle

by Christian Menge

Toxins 2020, 12(9), 607; https://doi.org/10.3390/toxins12090607 - 21 Sep 2020

Cited by 24 | Viewed by 5724

Abstract

Many cattle are persistently colonized with Shiga toxin-producing Escherichia coli (STEC) and represent a major source of human infections with human-pathogenic STEC strains (syn. enterohemorrhagic E. coli (EHEC)). Intervention strategies most effectively protecting humans best aim at the limitation of bovine STEC [...] Read more.

Many cattle are persistently colonized with Shiga toxin-producing Escherichia coli (STEC) and represent a major source of human infections with human-pathogenic STEC strains (syn. enterohemorrhagic E. coli (EHEC)). Intervention strategies most effectively protecting humans best aim at the limitation of bovine STEC shedding. Mechanisms enabling STEC to persist in cattle are only partialy understood. Cattle were long believed to resist the detrimental effects of Shiga toxins (Stxs), potent cytotoxins acting as principal virulence factors in the pathogenesis of human EHEC-associated diseases. However, work by different groups, summarized in this review, has provided substantial evidence that different types of target cells for Stxs exist in cattle. Peripheral and intestinal lymphocytes express the Stx receptor globotriaosylceramide (Gb₃syn. CD77) in vitro and in vivo in an activation-dependent fashion with Stx-binding isoforms expressed predominantly at early stages of the activation process. Subpopulations of colonic epithelial cells and macrophage-like cells, residing in the bovine mucosa in proximity to STEC colonies, are also targeted by Stxs. STEC-inoculated calves are depressed in mounting appropriate cellular immune responses which can be overcome by vaccination of the animals against Stxs early in life before encountering STEC. Considering Stx target cells and the resulting effects of Stxs in cattle, which significantly differ from effects implicated in human disease, may open promising opportunities to improve existing yet insufficient measures to limit STEC carriage and shedding by the principal reservoir host. Full article

(This article belongs to the Special Issue Molecular Basis and the Pathogenesis of Enterohemorrhagic Escherichia coli Infections)

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15 pages, 1159 KiB

Open AccessArticle

Antibiofilm Activity of Acidic Phospholipase Isoform Isolated from Bothrops erythromelas Snake Venom

by Ellynes Nunes, Breno Frihling, Elizângela Barros, Caio de Oliveira, Newton Verbisck, Taylla Flores, Augusto de Freitas Júnior, Octávio Franco, Maria de Macedo, Ludovico Migliolo and Karla Luna

Toxins 2020, 12(9), 606; https://doi.org/10.3390/toxins12090606 - 20 Sep 2020

Cited by 8 | Viewed by 3718

Abstract

Introduction: Bacterial resistance is a worldwide public health problem, requiring new therapeutic options. An alternative approach to this problem is the use of animal toxins isolated from snake venom, such as phospholipases A₂ (PLA₂), which have important antimicrobial activities. Bothrops [...] Read more.

Introduction: Bacterial resistance is a worldwide public health problem, requiring new therapeutic options. An alternative approach to this problem is the use of animal toxins isolated from snake venom, such as phospholipases A₂ (PLA₂), which have important antimicrobial activities. Bothropserythromelas is one of the snake species in the northeast of Brazil that attracts great medical-scientific interest. Here, we aimed to purify and characterize a PLA₂ from B. erythromelas, searching for heterologous activities against bacterial biofilms. Methods: Venom extraction and quantification were followed by reverse-phase high-performance liquid chromatography (RP-HPLC) in C18 column, matrix-assisted ionization time-of-flight (MALDI-ToF) mass spectrometry, and sequencing by Edman degradation. All experiments were monitored by specific activity using a 4-nitro-3-(octanoyloxy) benzoic acid (4N₃OBA) substrate. In addition, hemolytic tests and antibacterial tests including action against Escherichiacoli, Staphylococcusaureus, and Acinetobacterbaumannii were carried out. Moreover, tests of antibiofilm action against A. baumannii were also performed. Results: PLA₂, after one purification step, presented 31 N-terminal amino acid residues and a molecular weight of 13.6564 Da, with enzymatic activity confirmed in 0.06 µM concentration. Antibacterial activity against S. aureus (IC₅₀ = 30.2 µM) and antibiofilm activity against A. baumannii (IC₅₀ = 1.1 µM) were observed. Conclusions: This is the first time that PLA₂ purified from B. erythromelas venom has appeared as an alternative candidate in studies of new antibacterial medicines. Full article

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

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14 pages, 5237 KiB

Open AccessArticle

Reduction of Aflatoxin B₁ in Corn by Water-Assisted Microwaves Treatment and Its Effects on Corn Quality

by Yaolei Zhang, Mengmeng Li, Yuanxiao Liu, Erqi Guan and Ke Bian

Toxins 2020, 12(9), 605; https://doi.org/10.3390/toxins12090605 - 20 Sep 2020

Cited by 20 | Viewed by 3406

Abstract

Aflatoxin B₁ (AFB₁) is one of the most commonly found mycotoxin in corn, which is highly toxic, carcinogenic, teratogenic, and mutagenic for the health of humans and animals. In order to reduce the AFB₁ in corn, corn kernels were [...] Read more.

Aflatoxin B₁ (AFB₁) is one of the most commonly found mycotoxin in corn, which is highly toxic, carcinogenic, teratogenic, and mutagenic for the health of humans and animals. In order to reduce the AFB₁ in corn, corn kernels were processed with Water-assisted Microwaves Treatment (WMT) and the feasibility of WMT processing on AFB₁ reduction and its effects on corn quality were analyzed. Increasing the treatment time and microwave power could increase the reduction of AFB₁, and the maximum reduction rate could reach 58.6% and 56.8%, respectively. There was no significant correlation between the initial concentration of AFB₁ and the reduction rate of AFB₁. During WMT, the main toxigenic molds were sterilized completely, and the moisture content of corn climbed up and then declined to the initial level. WMT could obviously increase the fatty acid value and pasting temperature of corn and reduce the all paste viscosity of corn. However, it had little effect on the color of corn. The results indicated that WMT could reduce AFB₁ effectively and avoid the vast appearance of heat-damaged kernels simultaneously. Undoubtedly, water played an important role in WMT. This result provides a new idea for the reduction of AFB₁ by microwave. Full article

(This article belongs to the Section Mycotoxins)

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11 pages, 700 KiB

Open AccessArticle

Effects of Fumonisin-Contaminated Corn on Growth Performance of 9 to 28 kg Nursery Pigs

by Zhong-Xing Rao, Mike D. Tokach, Jason C. Woodworth, Joel M. DeRouchey, Robert D. Goodband, Hilda I. Calderón and Steve S. Dritz

Toxins 2020, 12(9), 604; https://doi.org/10.3390/toxins12090604 - 18 Sep 2020

Cited by 19 | Viewed by 3244

Abstract

Fumonisin contamination in corn is an emerging issue in animal feed production. Fumonisin disrupts the metabolism of sphingolipids and reduces growth performance. This experiment was conducted to determine the effect of feeding fumonisin-contaminated corn on growth performance and sphinganine (SA) to sphingosine (SO) [...] Read more.

Fumonisin contamination in corn is an emerging issue in animal feed production. Fumonisin disrupts the metabolism of sphingolipids and reduces growth performance. This experiment was conducted to determine the effect of feeding fumonisin-contaminated corn on growth performance and sphinganine (SA) to sphingosine (SO) ratios of 9 to 28 kg pigs. A total of 350 pigs, were used with 5 pigs/pen and 14 pens/treatment. Dietary treatments contained fumonisin-contaminated corn (50 mg/kg of fumonisin B1 + B2) blended with low fumonisin corn (10 mg/kg of fumonisin B1 + B2) to provide dietary fumonisin concentrations of 7.2, 14.7, 21.9, 32.7, and 35.1 mg/kg. From day 0 to 28, increasing fumonisin concentration decreased (linear, p < 0.001) average daily gain, average daily feed intake (linear, p = 0.055), and gain:feed ratio (linear, p = 0.016). Although these response criteria tested linear, the greatest reduction in performance was in pigs fed with 32.7 and 35.1 mg/kg of fumonisin (B1 + B2). Increasing fumonisin concentration increased the serum SA:SO ratio (linear, p < 0.001) on day 14 and 28. In summary, for 9 to 28 kg nursery pigs, increasing fumonisin linearly decreased average daily gain and gain:feed ratio. However, despite the linear response, diets containing up to 21.9 mg/kg of fumonisin did not have as dramatic a decrease in growth performance as those fed more than 32.7 mg/kg. Further research is warranted to determine the effect of fumonisin concentrations between 21.9 and 32.7 mg/kg. Full article

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

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13 pages, 2205 KiB

Open AccessArticle

Structural and Biochemical Characterization of Botulinum Neurotoxin Subtype B2 Binding to Its Receptors

by Jonathan R. Davies, Geoffrey Masuyer and Pål Stenmark

Toxins 2020, 12(9), 603; https://doi.org/10.3390/toxins12090603 - 17 Sep 2020

Cited by 6 | Viewed by 3773

Abstract

Botulinum neurotoxins (BoNTs) can be used therapeutically to treat a wide range of neuromuscular and neurological conditions. A collection of natural BoNT variants exists which can be classified into serologically distinct serotypes (BoNT/B), and further divided into subtypes (BoNT/B1, B2, …). BoNT subtypes [...] Read more.

Botulinum neurotoxins (BoNTs) can be used therapeutically to treat a wide range of neuromuscular and neurological conditions. A collection of natural BoNT variants exists which can be classified into serologically distinct serotypes (BoNT/B), and further divided into subtypes (BoNT/B1, B2, …). BoNT subtypes share a high degree of sequence identity within the same serotype yet can display large variation in toxicity. One such example is BoNT/B2, which was isolated from Clostridium botulinum strain 111 in a clinical case of botulism, and presents a 10-fold lower toxicity than BoNT/B1. In an effort to understand the molecular mechanisms behind this difference in potency, we here present the crystal structures of BoNT/B2 in complex with the ganglioside receptor GD1a, and with the human synaptotagmin I protein receptor. We show, using receptor-binding assays, that BoNT/B2 has a slightly higher affinity for GD1a than BoNT/B1, and confirm its considerably weaker affinity for its protein receptors. Although the overall receptor-binding mechanism is conserved for both receptors, structural analysis suggests the lower affinity of BoNT/B2 is the result of key substitutions, where hydrophobic interactions important for synaptotagmin-binding are replaced by polar residues. This study provides a template to drive the development of future BoNT therapeutic molecules centered on assessing the natural subtype variations in receptor-binding that appears to be one of the principal stages driving toxicity. Full article

(This article belongs to the Special Issue Selected Papers from the 26th Meeting of the French Society for Toxinology—Bioengineering of Toxins)

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10 pages, 1615 KiB

Open AccessBrief Report

Novel Binding Mechanisms of Fusion Broad Range Anti-Infective Protein Ricin A Chain Mutant-Pokeweed Antiviral Protein 1 (RTAM-PAP1) against SARS-CoV-2 Key Proteins in Silico

by Yasser Hassan, Sherry Ogg and Hui Ge

Toxins 2020, 12(9), 602; https://doi.org/10.3390/toxins12090602 - 17 Sep 2020

Cited by 4 | Viewed by 7485

Abstract

The deadly pandemic named COVID-19, caused by a new coronavirus (SARS-CoV-2), emerged in 2019 and is still spreading globally at a dangerous pace. As of today, there are no proven vaccines, therapies, or even strategies to fight off this virus. Here, we describe [...] Read more.

The deadly pandemic named COVID-19, caused by a new coronavirus (SARS-CoV-2), emerged in 2019 and is still spreading globally at a dangerous pace. As of today, there are no proven vaccines, therapies, or even strategies to fight off this virus. Here, we describe the in silico docking results of a novel broad range anti-infective fusion protein RTAM-PAP1 against the various key proteins of SARS-CoV-2 using the latest protein-ligand docking software. RTAM-PAP1 was compared against the SARS-CoV-2 B38 antibody, ricin A chain, a pokeweed antiviral protein from leaves, and the lectin griffithsin using the special CoDockPP COVID-19 version. These experiments revealed novel binding mechanisms of RTAM-PAP1 with a high affinity to numerous SARS-CoV-2 key proteins. RTAM-PAP1 was further characterized in a preliminary toxicity study in mice and was found to be a potential therapeutic candidate. These findings might lead to the discovery of novel SARS-CoV-2 targets and therapeutic protein structures with outstanding functions. Full article

(This article belongs to the Special Issue Toxin and Immunotoxin Based Therapeutic Approaches)

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5 pages, 193 KiB

Open AccessEditorial

Introduction to the Toxins Special Issue on Botulinum Neurotoxins in the Nervous System: Future Challenges for Novel Indications

by Siro Luvisetto

Toxins 2020, 12(9), 601; https://doi.org/10.3390/toxins12090601 - 17 Sep 2020

Cited by 2 | Viewed by 2166

Abstract

Botulinum toxins (BoNTs) are a true wonder of nature [...] Full article

(This article belongs to the Special Issue Botulinum Neurotoxins and Nervous System: Future Challenges for Novel Indications)

34 pages, 1985 KiB

Open AccessReview

Making 3D-Cry Toxin Mutants: Much More Than a Tool of Understanding Toxins Mechanism of Action

by Susana Vílchez

Toxins 2020, 12(9), 600; https://doi.org/10.3390/toxins12090600 - 16 Sep 2020

Cited by 18 | Viewed by 5257

Abstract

3D-Cry toxins, produced by the entomopathogenic bacterium Bacillus thuringiensis, have been extensively mutated in order to elucidate their elegant and complex mechanism of action necessary to kill susceptible insects. Together with the study of the resistant insects, 3D-Cry toxin mutants represent one [...] Read more.

3D-Cry toxins, produced by the entomopathogenic bacterium Bacillus thuringiensis, have been extensively mutated in order to elucidate their elegant and complex mechanism of action necessary to kill susceptible insects. Together with the study of the resistant insects, 3D-Cry toxin mutants represent one of the pillars to understanding how these toxins exert their activity on their host. The principle is simple, if an amino acid is involved and essential in the mechanism of action, when substituted, the activity of the toxin will be diminished. However, some of the constructed 3D-Cry toxin mutants have shown an enhanced activity against their target insects compared to the parental toxins, suggesting that it is possible to produce novel versions of the natural toxins with an improved performance in the laboratory. In this report, all mutants with an enhanced activity obtained by accident in mutagenesis studies, together with all the variants obtained by rational design or by directed mutagenesis, were compiled. A description of the improved mutants was made considering their historical context and the parallel development of the protein engineering techniques that have been used to obtain them. This report demonstrates that artificial 3D-Cry toxins made in laboratories are a real alternative to natural toxins. Full article

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

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17 pages, 2001 KiB

Open AccessArticle

First Detection of Tetrodotoxin in Bivalves and Gastropods from the French Mainland Coasts

by Vincent Hort, Nathalie Arnich, Thierry Guérin, Gwenaëlle Lavison-Bompard and Marina Nicolas

Toxins 2020, 12(9), 599; https://doi.org/10.3390/toxins12090599 - 16 Sep 2020

Cited by 36 | Viewed by 4211

Abstract

In 2015, tetrodotoxins (TTXs) were considered a potential threat in Europe since several studies had shown the presence of these toxins in European bivalve molluscs. In this study, we investigated the occurrence of TTXs in 127 bivalve samples (mussels and oysters) and in [...] Read more.

In 2015, tetrodotoxins (TTXs) were considered a potential threat in Europe since several studies had shown the presence of these toxins in European bivalve molluscs. In this study, we investigated the occurrence of TTXs in 127 bivalve samples (mussels and oysters) and in 66 gastropod samples (whelks) collected all along the French mainland coasts in 2017 and 2018. Analyses were carried out after optimization and in-house validation of a performing hydrophilic interaction liquid chromatography associated with tandem mass spectrometry (HILIC-MS/MS) method. The concentration set by European Food Safety Authority (EFSA) not expected to result in adverse effects (44 µg TTX equivalent/kg) was never exceeded, but TTX was detected in three mussel samples and one whelk sample (1.7–11.2 µg/kg). The tissue distribution of TTX in this whelk sample showed higher concentrations in the digestive gland, stomach and gonads (7.4 µg TTX/kg) than in the rest of the whelk tissues (below the limit of detection of 1.7 µg TTX/kg). This is the first study to report the detection of TTX in French molluscs. Full article

(This article belongs to the Special Issue Detection and Current Challenges in Marine and Freshwater Biotoxin Monitoring)

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23 pages, 15261 KiB

Open AccessArticle

An Investigation of Three-Finger Toxin—nAChR Interactions through Rosetta Protein Docking

by Alican Gulsevin and Jens Meiler

Toxins 2020, 12(9), 598; https://doi.org/10.3390/toxins12090598 - 16 Sep 2020

Cited by 8 | Viewed by 5216

Abstract

Three-finger toxins (3FTX) are a group of peptides that affect multiple receptor types. One group of proteins affected by 3FTX are nicotinic acetylcholine receptors (nAChR). Structural information on how neurotoxins interact with nAChR is limited and is confined to a small group of [...] Read more.

Three-finger toxins (3FTX) are a group of peptides that affect multiple receptor types. One group of proteins affected by 3FTX are nicotinic acetylcholine receptors (nAChR). Structural information on how neurotoxins interact with nAChR is limited and is confined to a small group of neurotoxins. Therefore, in silico methods are valuable in understanding the interactions between 3FTX and different nAChR subtypes, but there are no established protocols to model 3FTX–nAChR interactions. We followed a homology modeling and protein docking protocol to address this issue and tested its success on three different systems. First, neurotoxin peptides co-crystallized with acetylcholine binding protein (AChBP) were re-docked to assess whether Rosetta protein–protein docking can reproduce the native poses. Second, experimental data on peptide binding to AChBP was used to test whether the docking protocol can qualitatively distinguish AChBP-binders from non-binders. Finally, we docked eight peptides with known α7 and muscle-type nAChR binding properties to test whether the protocol can explain the differential activities of the peptides at the two receptor subtypes. Overall, the docking protocol predicted the qualitative and some specific aspects of 3FTX binding to nAChR with reasonable success and shed light on unknown aspects of 3FTX binding to different receptor subtypes. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)

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23 pages, 4103 KiB

Open AccessArticle

The Assessment of Diet Contaminated with Aflatoxin B₁ in Juvenile Turbot (Scophthalmus maximus) and the Evaluation of the Efficacy of Mitigation of a Yeast Cell Wall Extract

by Jinzhu Yang, Tiantian Wang, Gang Lin, Mingzhu Li, Ronghua Zhu, Alexandros Yiannikouris, Yanjiao Zhang and Kangsen Mai

Toxins 2020, 12(9), 597; https://doi.org/10.3390/toxins12090597 - 15 Sep 2020

Cited by 27 | Viewed by 4617

Abstract

This study aimed to investigate the effects of dietary AFB₁ on growth performance, health, intestinal microbiota communities and AFB₁ tissue residues of turbot and evaluate the mitigation efficacy of yeast cell wall extract, Mycosorb^® (YCWE) toward AFB₁ contaminated dietary [...] Read more.

This study aimed to investigate the effects of dietary AFB₁ on growth performance, health, intestinal microbiota communities and AFB₁ tissue residues of turbot and evaluate the mitigation efficacy of yeast cell wall extract, Mycosorb^® (YCWE) toward AFB₁ contaminated dietary treatments. Nine experimental diets were formulated: Diet 1 (control): AFB₁ free; Diets 2–5 or Diets 6–9: 20 μg AFB₁/kg diet or 500 μg AFB₁/kg diet + 0%, 0.1%, 0.2%, or 0.4% YCWE, respectively). The results showed that Diet 6 significantly decreased the concentrations of TP, GLB, C3, C4, T-CHO, TG but increased the activities of AST, ALT in serum, decreased the expressions of CAT, SOD, GPx, CYP1A but increased the expressions of CYP3A, GST-ζ₁, p53 in liver. Diet 6 increased the AFB₁ residues in serum and muscle, altered the intestinal microbiota composition, decreased the bacterial community diversity and the abundance of some potential probiotics. However, Diet 8 and Diet 9 restored the immune response, relieved adverse effects in liver, lowered the AFB₁ residues in turbot tissues, promoted intestinal microbiota diversity and lowered the abundance of potentially pathogens. In conclusion, YCWE supplementation decreased the health effects of AFB₁ on turbot, restoring biomarkers closer to the mycotoxin-free control diet. Full article

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

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14 pages, 4853 KiB

Open AccessArticle

Production of Highly Active Recombinant Dermonecrotic Toxin of Bordetella Pertussis

by Ondrej Stanek, Irena Linhartova, Jana Holubova, Ladislav Bumba, Zdenko Gardian, Anna Malandra, Barbora Bockova, Shihono Teruya, Yasuhiko Horiguchi, Radim Osicka and Peter Sebo

Toxins 2020, 12(9), 596; https://doi.org/10.3390/toxins12090596 - 15 Sep 2020

Cited by 1 | Viewed by 4662

Abstract

Pathogenic Bordetella bacteria release a neurotropic dermonecrotic toxin (DNT) that is endocytosed into animal cells and permanently activates the Rho family GTPases by polyamination or deamidation of the glutamine residues in their switch II regions (e.g., Gln63 of RhoA). DNT was found to [...] Read more.

Pathogenic Bordetella bacteria release a neurotropic dermonecrotic toxin (DNT) that is endocytosed into animal cells and permanently activates the Rho family GTPases by polyamination or deamidation of the glutamine residues in their switch II regions (e.g., Gln63 of RhoA). DNT was found to enable high level colonization of the nasal cavity of pigs by B. bronchiseptica and the capacity of DNT to inhibit differentiation of nasal turbinate bone osteoblasts causes atrophic rhinitis in infected pigs. However, it remains unknown whether DNT plays any role also in virulence of the human pathogen B. pertussis and in pathogenesis of the whooping cough disease. We report a procedure for purification of large amounts of LPS-free recombinant DNT that exhibits a high biological activity on cells expressing the DNT receptors Cav3.1 and Cav3.2. Electron microscopy and single particle image analysis of negatively stained preparations revealed that the DNT molecule adopts a V-shaped structure with well-resolved protein domains. These results open the way to structure–function studies on DNT and its interactions with airway epithelial layers. Full article

(This article belongs to the Section Bacterial Toxins)

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17 pages, 669 KiB

Open AccessArticle

Levels of Alternaria Toxins in Selected Food Commodities Including Green Coffee

by Claudia Mujahid, Marie-Claude Savoy, Quentin Baslé, Pei Mun Woo, Edith Chin Yean Ee, Pascal Mottier and Thomas Bessaire

Toxins 2020, 12(9), 595; https://doi.org/10.3390/toxins12090595 - 15 Sep 2020

Cited by 30 | Viewed by 4324

Abstract

Alternaria toxins are emerging mycotoxins, candidates for regulation by European Authorities. Therefore, highly sensitive, confirmatory, and reliable analytical methodologies are required for their monitoring in food. In that context, an isotope dilution LC-MS/MS method was developed for the analysis of five Alternaria toxins [...] Read more.

Alternaria toxins are emerging mycotoxins, candidates for regulation by European Authorities. Therefore, highly sensitive, confirmatory, and reliable analytical methodologies are required for their monitoring in food. In that context, an isotope dilution LC-MS/MS method was developed for the analysis of five Alternaria toxins (Altenuene, Alternariol, Alternariol monomethylether, Tentoxin, and Tenuazonic Acid) in a broad range of commodities including cereals and cereal-based products, tomato-based products, tree nuts, vegetable oils, dried fruits, cocoa, green coffee, spices, herbs, and tea. Validation data collected in two different laboratories demonstrated the robustness of the method. Underestimation of Tenuazonic Acid level in dry samples such as cereals was reported when inappropriate extraction solvent mixtures were used as currently done in several published methodologies. An investigation survey performed on 216 food items evidenced large variations of Alternaria toxins levels, in line with data reported in the last EFSA safety assessment. The analysis of 78 green coffee samples collected from 21 producing countries demonstrated that coffee is a negligible source of exposure to Alternaria toxins. Its wide scope of application, adequate sample throughput, and high sensitivity make this method fit for purpose for the regular monitoring of Alternaria toxins in foods. Full article

(This article belongs to the Special Issue Mycotoxins, Food Safety and Metrology)

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19 pages, 2109 KiB

Open AccessArticle

Bitis arietans Snake Venom Induces an Inflammatory Response Which Is Partially Dependent on Lipid Mediators

by Angela Alice Amadeu Megale, Fernanda Calheta Portaro and Wilmar Dias Da Silva

Toxins 2020, 12(9), 594; https://doi.org/10.3390/toxins12090594 - 14 Sep 2020

Cited by 8 | Viewed by 3705

Abstract

Bitis arietans is a snake of medical importance, as it is responsible for more accidents in humans and domestic animals than all other African snakes put together. The accidents are characterized by local and systemic alterations, such as inflammation, cardiovascular and hemostatic disturbances, [...] Read more.

Bitis arietans is a snake of medical importance, as it is responsible for more accidents in humans and domestic animals than all other African snakes put together. The accidents are characterized by local and systemic alterations, such as inflammation, cardiovascular and hemostatic disturbances, which can lead victims to death or permanent disability. However, little is known about the envenomation mechanism, especially regarding the inflammatory response, which is related to severe clinical conditions triggered by the venom. Therefore, the aim of the present study was to evaluate the inflammatory response related to the B. arietans envenomation using a peritonitis mice model. By pharmacological interventions and use of mice genetically deficient of the 5-lipoxygenase enzyme (5-LO^−/−) or platelet-activating factor (PAF) receptor (PAFR^−/− the participation of eicosanoids and PAF in this response was also investigated. The obtained results demonstrated that the venom induces an in vivo inflammatory response, characterized by an early increased vascular permeability, followed by an accumulation of polymorphonuclear (PMN) cells in the peritoneal cavity, accompanied by the production of the eicosanoids LTB₄, LTC₄, TXB₂ and PGE₂, as well as the local and systemic production of IL-6 and MCP-1. These inflammatory events were attenuated by the pre-treatment with anti-inflammatory drugs that interfere in lipid mediators’ functions. However, 5-LO^−/− mice did not show a reduction of inflammatory response induced by the venom, while PAFR^−/− mice showed a reduction in both the PMN leukocytes number and the local and systemic production of IL-6 and MCP-1. This study demonstrated that the Bitis arietans venom contains toxins that trigger an inflammatory process, which is partially dependent on lipid mediators, and may contribute to the envenomation pathology. Full article

(This article belongs to the Section Animal Venoms)

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28 pages, 8708 KiB

Open AccessArticle

Structural Modeling of Cell Wall Peptidase CwpFM (EntFM) Reveals Distinct Intrinsically Disordered Extensions Specific to Pathogenic Bacillus cereus Strains

by Seav-Ly Tran, Delphine Cormontagne, Jasmina Vidic, Gwenaëlle André-Leroux and Nalini Ramarao

Toxins 2020, 12(9), 593; https://doi.org/10.3390/toxins12090593 - 14 Sep 2020

Cited by 10 | Viewed by 3333

Abstract

The emergence of B. cereus as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with B. cereus infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, [...] Read more.

The emergence of B. cereus as an opportunistic food-borne pathogen has intensified the need to distinguish strains of public health concern. The heterogeneity of the diseases associated with B. cereus infections emphasizes the versatility of these bacteria strains to colonize their host. Nevertheless, the molecular basis of these differences remains unclear. Several toxins are involved in virulence, particularly in gastrointestinal disorders, but there are currently no biological markers able to differentiate pathogenic from harmless strains. We have previously shown that CwpFM is a cell wall peptidase involved in B. cereus virulence. Here, we report a sequence/structure/function characterization of 39 CwpFM sequences, chosen from a collection of B. cereus with diverse virulence phenotypes, from harmless to highly pathogenic strains. CwpFM is homology-modeled in silico as an exported papain-like endopeptidase, with an N-terminal end composed of three successive bacterial Src Homology 3 domains (SH3b_1–3) likely to control protein–protein interactions in signaling pathways, and a C-terminal end that contains a catalytic NLPC_P60 domain primed to form a competent active site. We confirmed in vitro that CwpFM is an endopeptidase with a moderate peptidoglycan hydrolase activity. Remarkably, CwpFMs from pathogenic strains harbor a specific stretch of twenty residues intrinsically disordered, inserted between the SH3b₃ and the catalytic NLPC_P60 domain. This strongly suggests this linker as a marker of differentiation between B. cereus strains. We believe that our findings improve our understanding of the pathogenicity of B. cereus while advancing both clinical diagnosis and food safety. Full article

(This article belongs to the Special Issue Bacillus cereus Toxins)

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15 pages, 476 KiB

Open AccessArticle

Genetic Diversity, Ochratoxin A and Fumonisin Profiles of Strains of Aspergillus Section Nigri Isolated from Dried Vine Fruits

by Petra Mikušová, Miroslav Caboň, Andrea Melichárková, Martin Urík, Alberto Ritieni and Marek Slovák

Toxins 2020, 12(9), 592; https://doi.org/10.3390/toxins12090592 - 14 Sep 2020

Cited by 11 | Viewed by 3079

Abstract

We investigated ochratoxin A (OTA) contamination in raisin samples purchased from Slovak markets and determined the diversity of black-spored aspergilli as potential OTA and fumonisin (FB1 and FB2) producers. The taxonomic identification was performed using sequences of the nuclear ITS1-5.8s-ITS2 region, the calmodulin [...] Read more.

We investigated ochratoxin A (OTA) contamination in raisin samples purchased from Slovak markets and determined the diversity of black-spored aspergilli as potential OTA and fumonisin (FB1 and FB2) producers. The taxonomic identification was performed using sequences of the nuclear ITS1-5.8s-ITS2 region, the calmodulin and beta-tubulin genes. We obtained 239 isolates from eight fungal genera, of which 197 belonged to Aspergillus (82%) and 42 strains (18%) to other fungal genera. OTA contamination was evidenced in 75% of the samples and its level ranged from 0.8 to 10.6 µg/kg. The combination of all three markers used enabled unambiguous identification of A. carbonarius, A. luchuensis, A. niger, A. tubingensis and A. welwitschiae. The dominant coloniser, simultaneously having the highest within-species diversity isolated from our raisin samples, was A. tubingensis. Out of all analysed strains, only A. carbonarius was found to produce OTA, but in relatively high quantity (2477–4382 µg/kg). The production of FB1 and FB2 was evidenced in A. niger strains only. Full article

(This article belongs to the Special Issue Mycotoxins and Food)

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16 pages, 1337 KiB

Open AccessArticle

Biomonitoring of Aflatoxin B₁ and Deoxynivalenol in a Rural Pakistan Population Using Ultra-Sensitive LC-MS/MS Method

by Lei Xia, Michael N. Routledge, Hifza Rasheed, Amir Ismail, Yao Dong, Tao Jiang and Yun Yun Gong

Toxins 2020, 12(9), 591; https://doi.org/10.3390/toxins12090591 - 12 Sep 2020

Cited by 10 | Viewed by 8483

Abstract

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B₁ (AFB₁), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) [...] Read more.

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B₁ (AFB₁), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB₁ and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4–80 years, male 58%) using ultra-sensitive liquid chromatography–tandem mass spectrometry. AFB₁ was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM₁ (hydroxylated form of AFB₁) was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives’ tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/10⁵ individuals/year suggests that measures should be taken to reduce the AFB₁ contamination in food, particularly rice, in Pakistan. Full article

(This article belongs to the Special Issue Biomonitoring of Mycotoxins)

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20 pages, 1447 KiB

Open AccessReview

Gut-Derived Protein-Bound Uremic Toxins

by Amanda L. Graboski and Matthew R. Redinbo

Toxins 2020, 12(9), 590; https://doi.org/10.3390/toxins12090590 - 11 Sep 2020

Cited by 80 | Viewed by 8933

Abstract

Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from [...] Read more.

Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from cardiovascular disease and other causes. Several of the most harmful uremic toxins are produced by the gut microbiota. Furthermore, many such toxins are protein-bound and are therefore recalcitrant to removal by dialysis. We review the derivation and pathological mechanisms of gut-derived, protein-bound uremic toxins (PBUTs). We further outline the emerging relationship between kidney disease and gut dysbiosis, including the bacterial taxa altered, the regulation of microbial uremic toxin-producing genes, and their downstream physiological and neurological consequences. Finally, we discuss gut-targeted therapeutic strategies employed to reduce PBUTs. We conclude that targeting the gut microbiota is a promising approach for the treatment of CKD by blocking the serum accumulation of PBUTs that cannot be eliminated by dialysis. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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13 pages, 744 KiB

Open AccessCommunication

Antinociceptive Activity of the Skin Secretion of Phyllomedusa rohdei (Amphibia, Anura)

by Elena Lucia Anna Malpezzi-Marinho, Cristiane Isabel Silva Zanoni, Graziella Rigueira Molska, Camila Paraventi, Raphael Wuo-Silva, Laís Fernanda Berro, Carlos Amilcar Parada, Eduardo Koji Tamura and Eduardo Ary Villela Marinho

Toxins 2020, 12(9), 589; https://doi.org/10.3390/toxins12090589 - 11 Sep 2020

Cited by 4 | Viewed by 3216

Abstract

Pain is a distressful experience that can have a major impact on an individual’s quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to [...] Read more.

Pain is a distressful experience that can have a major impact on an individual’s quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to contain bioactive peptides that exert analgesic effects. The genus Phyllomedusa represents an important source of peptides and bioactive components. The aim of this study was to investigate the antinociceptive effects of the skin secretion of Phyllomedusa rohdei in rodent models of pain. The crude skin extract of P. rohdei was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE₂ (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of P. rohdei exerted antinociceptive effects in all pain models tested. Particularly, the highest dose tested of the skin extract decreased acetic acid-induced writhing by 93%, completely blocked formalin-induced nociception both during the acute and inflammatory phases of the test, PGE₂-induced hypernociception by 73% and increased latency to paw withdrawal in the hot plate test by 300%. The effects observed in the hot plate test were reversed by pretreatment with selective µ and κ, but not δ, opioid receptor antagonists, indicating a mechanism of action dependent on µ and κ opioid receptors. The results were not influenced by sedative effects. Further studies remain necessary to reveal the specific compounds involved in the antinociceptive effects of P. rohdei skin extract as a new therapeutic tool in pain management. Full article

(This article belongs to the Special Issue Amphibian Toxins and Poisons)

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10 pages, 3013 KiB

Open AccessArticle

Comparison between Conventional Blind Injections and Ultrasound-Guided Injections of Botulinum Toxin Type A into the Masseter: A Clinical Trial

by Hyungkyu Bae, Jisoo Kim, Kyle K. Seo, Kyung-Seok Hu, Seong-Taek Kim and Hee-Jin Kim

Toxins 2020, 12(9), 588; https://doi.org/10.3390/toxins12090588 - 11 Sep 2020

Cited by 22 | Viewed by 5155

Abstract

The aim of the study was to propose a more efficient and safer botulinum toxin type A (BoNT-A) injection method for the masseter by comparing the conventional blind injection and a novel ultrasonography (US)-guided injection technique in a clinical trial. The 40 masseters [...] Read more.

The aim of the study was to propose a more efficient and safer botulinum toxin type A (BoNT-A) injection method for the masseter by comparing the conventional blind injection and a novel ultrasonography (US)-guided injection technique in a clinical trial. The 40 masseters from 20 healthy young Korean volunteers (10 males and 10 females with a mean age of 25.6 years) were included in this prospective clinical trial. The BoNT-A (24 U) was injected into the masseter of each volunteer using the conventional blind and US-guided injection techniques on the left and right sides, respectively, and analyzed by US and three-dimensional (3D) facial scanning. One case of PMB (paradoxical masseteric bulging) was observed on the side where a conventional blind injection was performed, which disappeared after the compensational injection. The reduction in the thickness of the masseter in the resting state differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 12.38 ± 7.59% and 17.98 ± 9.65%, respectively (t(19) = 3.059, p = 0.007). The reduction in the facial contour also differed significantly at 1 month after the injection between the conventional blind injection group and the US-guided injection group by 1.95 ± 0.74 mm and 2.22 ± 0.84 mm, respectively (t(19) = 2.908, p = 0.009). The results of the study showed that the US-guided injection method that considers the deep inferior tendon by visualizing the masseter can prevent the PMB that can occur during a blind injection, and is also more effective. Full article

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

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14 pages, 2293 KiB

Open AccessArticle

Acetamiprid Affects Destruxins Production but Its Accumulation in Metarhizium sp. Spores Increases Infection Ability of Fungi

by Monika Nowak, Przemysław Bernat, Julia Mrozińska and Sylwia Różalska

Toxins 2020, 12(9), 587; https://doi.org/10.3390/toxins12090587 - 11 Sep 2020

Cited by 9 | Viewed by 3071

Abstract

Metarhizium sp. are entomopathogenic fungi that inhabit the soil environment. Together, they act as natural pest control factors. In the natural environment, they come into contact with various anthropogenic pollutants, and sometimes, they are used together and interchangeably with chemical insecticides (e.g., neonicotinoids) [...] Read more.

Metarhizium sp. are entomopathogenic fungi that inhabit the soil environment. Together, they act as natural pest control factors. In the natural environment, they come into contact with various anthropogenic pollutants, and sometimes, they are used together and interchangeably with chemical insecticides (e.g., neonicotinoids) for pest control. In most cases, the compatibility of entomopathogens with insecticides has been determined; however, the influence of these compounds on the metabolism of entomopathogenic fungi has not yet been studied. Secondary metabolites are very important factors that influence the fitness of the producers, playing important roles in the ability of these pathogens to successfully parasitize insects. In this study, for the first time, we focus on whether the insecticide present in the fungal growth environment affects secondary metabolism in fungi. The research revealed that acetamiprid at concentrations from 5 to 50 mg L⁻¹ did not inhibit the growth of all tested Metarhizium sp.; however, it reduced the level of 19 produced destruxins in direct proportion to the dosage used. Furthermore, it was shown that acetamiprid accumulates not only in plant or animal tissues, but also in fungal cells. Despite the negative impact of acetamiprid on secondary metabolism, it was proofed to accumulate in Metarhizium spores, which appeared to have a stronger infectious potential against mealworm Tenebrio molitor, in comparison to the insecticide or the biological agent alone. Full article

(This article belongs to the Special Issue Mycotoxins Study: Toxicology, Identification and Control)

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26 pages, 2492 KiB

Open AccessArticle

Diversity of the Genomes and Neurotoxins of Strains of Clostridium botulinum Group I and Clostridium sporogenes Associated with Foodborne, Infant and Wound Botulism

by Jason Brunt, Arnoud H. M. van Vliet, Andrew T. Carter, Sandra C. Stringer, Corinne Amar, Kathie A. Grant, Gauri Godbole and Michael W. Peck

Toxins 2020, 12(9), 586; https://doi.org/10.3390/toxins12090586 - 11 Sep 2020

Cited by 32 | Viewed by 6946

Abstract

Clostridium botulinum Group I and Clostridium sporogenes are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of C. botulinum Group I and C. sporogenes (including 417 newly sequenced strains) has been carried [...] Read more.

Clostridium botulinum Group I and Clostridium sporogenes are closely related bacteria responsible for foodborne, infant and wound botulism. A comparative genomic study with 556 highly diverse strains of C. botulinum Group I and C. sporogenes (including 417 newly sequenced strains) has been carried out to characterise the genetic diversity and spread of these bacteria and their neurotoxin genes. Core genome single-nucleotide polymorphism (SNP) analysis revealed two major lineages; C. botulinum Group I (most strains possessed botulinum neurotoxin gene(s) of types A, B and/or F) and C. sporogenes (some strains possessed a type B botulinum neurotoxin gene). Both lineages contained strains responsible for foodborne, infant and wound botulism. A new C. sporogenes cluster was identified that included five strains with a gene encoding botulinum neurotoxin sub-type B1. There was significant evidence of horizontal transfer of botulinum neurotoxin genes between distantly related bacteria. Population structure/diversity have been characterised, and novel associations discovered between whole genome lineage, botulinum neurotoxin sub-type variant, epidemiological links to foodborne, infant and wound botulism, and geographic origin. The impact of genomic and physiological variability on the botulism risk has been assessed. The genome sequences are a valuable resource for future research (e.g., pathogen biology, evolution of C. botulinum and its neurotoxin genes, improved pathogen detection and discrimination), and support enhanced risk assessments and the prevention of botulism. Full article

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

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22 pages, 6263 KiB

Open AccessArticle

[D-Leu¹]MC-LR and MC-LR: A Small–Large Difference: Significantly Different Effects on Phaseolus vulgaris L. (Fabaceae) Growth and Phototropic Response after Single Contact during Imbibition with Each of These Microcystin Variants

by Luciano Malaissi, Cristian Adrián Vaccarini, Marcelo Paulo Hernández, Marcela Ruscitti, Cecilia Arango, Federico Busquets, Ana María Arambarri, Leda Giannuzzi, Darío Andrinolo and Daniela Sedan

Toxins 2020, 12(9), 585; https://doi.org/10.3390/toxins12090585 - 11 Sep 2020

Cited by 13 | Viewed by 3304

Abstract

[D-Leu¹]MC-LR and MC-LR, two microcystins differing in one amino acid, constitute a sanitary and environmental problem owing to their frequent and concomitant presence in water bodies of the Americas and their association with human intoxication during recreational exposure to cyanobacterial bloom. [...] Read more.

[D-Leu¹]MC-LR and MC-LR, two microcystins differing in one amino acid, constitute a sanitary and environmental problem owing to their frequent and concomitant presence in water bodies of the Americas and their association with human intoxication during recreational exposure to cyanobacterial bloom. Present in reservoirs used for irrigation as well, they can generate problems in the development of crops such as Phaseolus vulgaris, of nutritional and economic interest to the region. Although numerous works address the toxic effects of MC-LR, information on the toxicity of [D-Leu¹]MC-LR is limited. Our objective was to study the toxic effects of [D-Leu¹]MC-LR and MC-LR (3.5 µg/ml) on P. vulgaris after a single contact at the imbibition stage. Our findings indicate that 10 days post treatment, [D-Leu¹]MC-LR generates morphological and physiological alterations more pronounced than those caused by MC-LR. In addition to the alterations produced by [D-Leu¹]MC-LR in the development of seedlings and the structure of the leaves, roots and stems, we also found alterations in leaf stomatal density and conductivity, a longer delay in the phototropic response and a decrease in the maximum curvature angles achieved with respect to that observed for MC-LR. Our findings indicate that these alterations are linked to the greater inhibition of phosphatase activity generated by [D-Leu¹]MC-LR, rather than to oxidative damage. We observed that 30 days after treatment with MC-LR, plants presented better development and recovery than those treated with [D-Leu¹]MC-LR. Further studies are required on [D-Leu¹]MC-LR and MC-LR toxicity and their underlying mechanisms of action. Full article

(This article belongs to the Special Issue Selected Papers from the 6th Iberian and 2nd Ibero-American Cyanotoxin Congress CIC2019)

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18 pages, 2766 KiB

Open AccessReview

Staphylococcal Enterotoxin C—An Update on SEC Variants, Their Structure and Properties, and Their Role in Foodborne Intoxications

by Danai Etter, Jenny Schelin, Markus Schuppler and Sophia Johler

Toxins 2020, 12(9), 584; https://doi.org/10.3390/toxins12090584 - 10 Sep 2020

Cited by 34 | Viewed by 10887

Abstract

Staphylococcal enterotoxins are the most common cause of foodborne intoxications (staphylococcal food poisoning) and cause a wide range of diseases. With at least six variants staphylococcal enterotoxin C (SEC) stands out as particularly diverse amongst the 25 known staphylococcal enterotoxins. Some variants present [...] Read more.

Staphylococcal enterotoxins are the most common cause of foodborne intoxications (staphylococcal food poisoning) and cause a wide range of diseases. With at least six variants staphylococcal enterotoxin C (SEC) stands out as particularly diverse amongst the 25 known staphylococcal enterotoxins. Some variants present unique and even host-specific features. Here, we review the role of SEC in human and animal health with a particular focus on its role as a causative agent for foodborne intoxications. We highlight structural features unique to SEC and its variants, particularly, the emetic and superantigen activity, as well as the roles of SEC in mastitis and in dairy products. Information about the genetic organization as well as regulatory mechanisms including the accessory gene regulator and food-related stressors are provided. Full article

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

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15 pages, 549 KiB

Open AccessReview

Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite

by Supun Wedasingha, Geoffrey Isbister and Anjana Silva

Toxins 2020, 12(9), 583; https://doi.org/10.3390/toxins12090583 - 10 Sep 2020

Cited by 31 | Viewed by 6376

Abstract

Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in [...] Read more.

Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in diagnosing coagulopathy in low-income settings, where the majority of snakebites occur. We conducted a literature search in MEDLINE^® from 1946 to 30 November 2019, looking for research articles describing clinical studies on bedside coagulation tests in snakebite patients. Out of 442 articles identified, 147 articles describing bedside clotting assays were included in the review. Three main bedside clotting tests were identified, namely the Lee–White clotting test, 20-min whole blood clotting time and venous clotting time. Although the original Lee–White clotting test has never been validated for snake envenoming, a recently validated version has been used in some South American countries. The 20-min whole blood clotting time test is the most commonly used test in a wide range of settings and for taxonomically diverse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small sample size, lack of case-authentication, the inclusion of a heterogeneous mix of snakebites and inappropriate uses of gold standard tests. The observation times for bedside clotting tests were arbitrary, without proper scientific justification. Future research needs to focus on improving the existing 20-min whole blood clotting test, and also on looking for alternative bedside coagulation tests which are cheap, reliable and quicker. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 2939 KiB

Open AccessArticle

Redox-Sensitive Nanocomplex for Targeted Delivery of Melittin

by Bei Cheng and Peisheng Xu

Toxins 2020, 12(9), 582; https://doi.org/10.3390/toxins12090582 - 10 Sep 2020

Cited by 21 | Viewed by 3988

Abstract

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and [...] Read more.

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes will provide a new approach for melittin based cancer therapy. Full article

(This article belongs to the Special Issue Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics)

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11 pages, 1648 KiB

Open AccessReview

Consequences of Metabolic Interactions during Staphylococcus aureus Infection

by Tania Wong Fok Lung and Alice Prince

Toxins 2020, 12(9), 581; https://doi.org/10.3390/toxins12090581 - 9 Sep 2020

Cited by 26 | Viewed by 6833

Abstract

Staphylococcus aureus is a metabolically flexible pathogen that causes infection in diverse settings. An array of virulence factors, including the secreted toxins, enables S. aureus to colonize different environmental niches and initiate infections by any of several discrete pathways. During these infections, both [...] Read more.

Staphylococcus aureus is a metabolically flexible pathogen that causes infection in diverse settings. An array of virulence factors, including the secreted toxins, enables S. aureus to colonize different environmental niches and initiate infections by any of several discrete pathways. During these infections, both S. aureus and host cells compete with each other for nutrients and remodel their metabolism for survival. This metabolic interaction/crosstalk determines the outcome of the infection. The reprogramming of metabolic pathways in host immune cells not only generates adenosine triphosphate (ATP) to meet the cellular energy requirements during the infection process but also activates antimicrobial responses for eventual bacterial clearance, including cell death pathways. The selective pressure exerted by host immune cells leads to the emergence of bacterial mutants adapted for chronicity. These host-adapted mutants are often characterized by substantial changes in the expression of their own metabolic genes, or by mutations in genes involved in metabolism and biofilm formation. Host-adapted S. aureus can rewire or benefit from the metabolic activities of the immune cells via several mechanisms to cause persistent infection. In this review, we discuss how S. aureus activates host innate immune signaling, which results in an immune metabolic pressure that shapes S. aureus metabolic adaptation and determines the outcome of the infection. Full article

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

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18 pages, 2309 KiB

Open AccessArticle

Is a Central Sediment Sample Sufficient? Exploring Spatial and Temporal Microbial Diversity in a Small Lake

by Barbara Weisbrod, Susanna A. Wood, Konstanze Steiner, Ruby Whyte-Wilding, Jonathan Puddick, Olivier Laroche and Daniel R. Dietrich

Toxins 2020, 12(9), 580; https://doi.org/10.3390/toxins12090580 - 9 Sep 2020

Cited by 11 | Viewed by 3899

Abstract

(1) Background: Paleolimnological studies use sediment cores to explore long-term changes in lake ecology, including occurrences of harmful cyanobacterial blooms. Most studies are based on single cores, assuming this is representative of the whole lake, but data on small-scale spatial variability of microbial [...] Read more.

(1) Background: Paleolimnological studies use sediment cores to explore long-term changes in lake ecology, including occurrences of harmful cyanobacterial blooms. Most studies are based on single cores, assuming this is representative of the whole lake, but data on small-scale spatial variability of microbial communities in lake sediment are scarce. (2) Methods: Surface sediments (top 0.5 cm) from 12 sites (n = 36) and two sediment cores were collected in Lake Rotorua (New Zealand). Bacterial community (16S rRNA metabarcoding), Microcystis specific 16S rRNA, microcystin synthetase gene E (mcyE) and microcystins (MCs) were assessed. Radionuclide measurements (²¹⁰Pb, ¹³⁷Cs) were used to date sediments. (3) Results: Bacterial community, based on relative abundances, differed significantly between surface sediment sites (p < 0.001) but the majority of bacterial amplicon sequence variants (88.8%) were shared. Despite intense MC producing Microcystis blooms in the past, no Microcystis specific 16S rRNA, mcyE and MCs were found in surface sediments but occurred deeper in sediment cores (approximately 1950′s). ²¹⁰Pb measurements showed a disturbed profile, similar to patterns previously observed, as a result of earthquakes. (4) Conclusions: A single sediment core can capture dominant microbial communities. Toxin producing Microcystis blooms are a recent phenomenon in Lake Rotorua. We posit that the absence of Microcystis from the surface sediments is a consequence of the Kaikoura earthquake two years prior to our sampling. Full article

(This article belongs to the Special Issue Cyanotoxins in Bloom: Ever-Increasing Occurrence and Global Distribution of Freshwater Cyanotoxins from Planktic and Benthic Cyanobacteria)

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14 pages, 3118 KiB

Open AccessArticle

The Influence of Calcium toward Order/Disorder Conformation of Repeat-in-Toxin (RTX) Structure of Family I.3 Lipase from Pseudomonas fluorescens AMS8

by Nur Shidaa Mohd Ali, Abu Bakar Salleh, Thean Chor Leow, Raja Noor Zaliha Raja Abd Rahman and Mohd Shukuri Mohamad Ali

Toxins 2020, 12(9), 579; https://doi.org/10.3390/toxins12090579 - 9 Sep 2020

Cited by 3 | Viewed by 2711

Abstract

Calcium-binding plays a decisive role in the folding and stabilization of many RTX proteins, especially for the RTX domain. Although many studies have been conducted to prove the contribution of Ca²⁺ ion toward the folding and stabilization of RTX proteins, its functional [...] Read more.

Calcium-binding plays a decisive role in the folding and stabilization of many RTX proteins, especially for the RTX domain. Although many studies have been conducted to prove the contribution of Ca²⁺ ion toward the folding and stabilization of RTX proteins, its functional dynamics and conformational structural changes remain elusive. Here, molecular docking and molecular dynamics (MD) simulations were performed to analyze the contribution of Ca²⁺ ion toward the folding and stabilization of the RTX lipase (AMS8 lipase) structure. AMS8 lipase contains six Ca²⁺ ions (Ca1–Ca6). Three Ca²⁺ ions (Ca3, Ca4, and Ca5) were bound to the RTX parallel β-roll motif repeat structure (RTX domain). The metal ion (Ca²⁺) docking analysis gives a high binding energy, especially for Ca4 and Ca5 which are tightly bound to the RTX domain. The function of each Ca²⁺ ion is further analyzed using the MD simulation. The removal of Ca3, Ca4, and Ca5 caused the AMS8 lipase structure to become unstable and unfolded. The results suggested that Ca3, Ca4, and Ca5 stabilized the RTX domain. In conclusion, Ca3, Ca4, and Ca5 play a crucial role in the folding and stabilization of the RTX domain, which sustain the integrity of the overall AMS8 lipase structure. Full article

(This article belongs to the Special Issue Bacterial Toxins: Protein Folding and Membrane Interactions)

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