Toxins

9 pages, 2355 KiB

Open AccessEditor’s ChoiceArticle

A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen

by Silva Rubini, Sabina Strano Rossi, Serena Mestria, Sara Odoardi, Sara Chendi, Andrea Poli, Giuseppe Merialdi, Giuseppina Andreoli, Paolo Frisoni, Rosa Maria Gaudio, Anna Baldisserotto, Piergiacomo Buso, Stefano Manfredini, Guido Govoni, Stefania Barbieri, Cinzia Centelleghe, Giorgia Corazzola, Sandro Mazzariol and Carlo Alessandro Locatelli

Toxins 2019, 11(8), 442; https://doi.org/10.3390/toxins11080442 - 25 Jul 2019

Cited by 15 | Viewed by 7606

Abstract

Oleander (Nerium oleander) is an ornamental plant common in tropical and sub-tropical regions that is becoming increasingly widespread, even in temperate regions. Oleander poisoning may occur in animals and humans. The main active components contained in the plant are cardiac glycosides [...] Read more.

Oleander (Nerium oleander) is an ornamental plant common in tropical and sub-tropical regions that is becoming increasingly widespread, even in temperate regions. Oleander poisoning may occur in animals and humans. The main active components contained in the plant are cardiac glycosides belonging to the class of cardenolides that are toxic to many species, from human to insects. This work describes a case of oleander poisoning that occurred on a small cattle farm and resulted in the fatality of all six resident animals. Furthermore, the investigation of the poisonous agent is described, with particular focus on the characterization of the oleandrin toxin that was recovered from the forage and rumen contents. The innovation of this study is the first description of the detection and quantification of the oleandrin toxin by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in rumen. Full article

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

► Show Figures

Figure 1

20 pages, 5960 KiB

Open AccessEditor’s ChoiceArticle

Diversity, Cyanotoxin Production, and Bioactivities of Cyanobacteria Isolated from Freshwaters of Greece

by Spyros Gkelis, Manthos Panou, Despoina Konstantinou, Panagiotis Apostolidis, Antonia Kasampali, Sofia Papadimitriou, Dominiki Kati, Giorgia Maria Di Lorenzo, Stamatia Ioakeim, Sevasti-Kiriaki Zervou, Christophoros Christophoridis, Theodoros M. Triantis, Triantafyllos Kaloudis, Anastasia Hiskia and Minas Arsenakis

Toxins 2019, 11(8), 436; https://doi.org/10.3390/toxins11080436 - 25 Jul 2019

Cited by 32 | Viewed by 6646

Abstract

Cyanobacteria are a diverse group of photosynthetic Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against a broad spectrum of organisms and cell lines. In this study, 29 strains isolated from freshwaters in Greece were classified using a polyphasic [...] Read more.

Cyanobacteria are a diverse group of photosynthetic Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against a broad spectrum of organisms and cell lines. In this study, 29 strains isolated from freshwaters in Greece were classified using a polyphasic approach and assigned to Chroococcales, Synechococcales, and Nostocales, representing 11 genera and 17 taxa. There were good agreements between 16S ribosomal RNA (rRNA)–cpcBA–internal genetic spacer (IGS) characterization and morphological features, except for the Jaaginema–Limnothrix group which appears intermixed and needs further elucidation. Methanol extracts of the strains were analyzed for cyanotoxin production and tested against pathogenic bacteria species and several cancer cell lines. We report for the first time a Nostoc oryzae strain isolated from rice fields capable of producing microcystins (MCs) and a Chlorogloeopsis fritschii strain isolated from the plankton of a lake, suggesting that this species may also occur in freshwater temperate habitats. Strains with very high or identical 16S rRNA gene sequences displayed different antibacterial and cytotoxic activities. Extracts from Synechococcus cf. nidulans showed the most potent antibacterial activity against Staphylococcus aureus, whereas Jaaginema sp. strains exhibited potent cytotoxic activities against human colorectal adenocarcinoma and hepatocellular carcinoma cells. Jaaginema Thessaloniki Aristotle University Microalgae and Cyanobacteria (TAU-MAC) 0110 and 0210 strains caused pronounced changes in the actin network and triggered the formation of numerous lipid droplets in hepatocellular carcinoma and green monkey kidney cells, suggesting oxidative stress and/or mitochondrial damage leading to apoptosis. Full article

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

► Show Figures

Figure 1

22 pages, 2732 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Phase I and Glucuronide Phase II Metabolites of 17 Mycotoxins Using Liquid Chromatography—High-Resolution Mass Spectrometry

by Irina Slobodchikova, Reajean Sivakumar, Md Samiur Rahman and Dajana Vuckovic

Toxins 2019, 11(8), 433; https://doi.org/10.3390/toxins11080433 - 24 Jul 2019

Cited by 18 | Viewed by 5676

Abstract

Routine mycotoxin biomonitoring methods do not include many mycotoxin phase I and phase II metabolites, which may significantly underestimate mycotoxin exposure especially for heavily metabolized mycotoxins. Additional research efforts are also needed to measure metabolites in vivo after exposure and to establish which [...] Read more.

Routine mycotoxin biomonitoring methods do not include many mycotoxin phase I and phase II metabolites, which may significantly underestimate mycotoxin exposure especially for heavily metabolized mycotoxins. Additional research efforts are also needed to measure metabolites in vivo after exposure and to establish which mycotoxin metabolites should be prioritized for the inclusion during large-scale biomonitoring efforts. The objective of this study was to perform human in vitro microsomal incubations of 17 mycotoxins and systematically characterize all resulting metabolites using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). The results obtained were then used to build a comprehensive LC-MS library and expand a validated 17-mycotoxin method for exposure monitoring to screening of additional 188 metabolites, including 100 metabolites reported for the first time. The final method represents one of the most comprehensive LC-HRMS methods for mycotoxin biomonitoring or metabolism/fate studies. Full article

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

► Show Figures

Graphical abstract

16 pages, 1060 KiB

Open AccessEditor’s ChoiceArticle

Target Analysis and Retrospective Screening of Multiple Mycotoxins in Pet Food Using UHPLC-Q-Orbitrap HRMS

by Luigi Castaldo, Giulia Graziani, Anna Gaspari, Luana Izzo, Josefa Tolosa, Yelko Rodríguez-Carrasco and Alberto Ritieni

Toxins 2019, 11(8), 434; https://doi.org/10.3390/toxins11080434 - 24 Jul 2019

Cited by 29 | Viewed by 4139

Abstract

A comprehensive strategy combining a quantitative method for 28 mycotoxins and a post-target screening for other 245 fungal and bacterial metabolites in dry pet food samples were developed using an acetonitrile-based extraction and an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-Q-Orbitrap [...] Read more.

A comprehensive strategy combining a quantitative method for 28 mycotoxins and a post-target screening for other 245 fungal and bacterial metabolites in dry pet food samples were developed using an acetonitrile-based extraction and an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method. The proposed method showed satisfactory validation results according to Commission Decision 2002/657/EC. Average recoveries from 72 to 108% were obtained for all studied mycotoxins, and the intra-/inter-day precision were below 9 and 14%, respectively. Results showed mycotoxin contamination in 99% of pet food samples (n = 89) at concentrations of up to hundreds µg/kg, with emerging Fusarium mycotoxins being the most commonly detected mycotoxins. All positive samples showed co-occurrence of mycotoxins with the simultaneous presence of up to 16 analytes per sample. In the retrospective screening, up to 54 fungal metabolites were tentatively identified being cyclopiazonic acid, paspalitrem A, fusaric acid, and macrosporin, the most commonly detected analytes. Full article

(This article belongs to the Special Issue Mycotoxin Contamination Management Tools and Efficient Strategies in Feed Industry)

► Show Figures

Figure 1

15 pages, 1544 KiB

Open AccessEditor’s ChoiceArticle

Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients

by Djurdja Jerotic, Marija Matic, Sonja Suvakov, Katarina Vucicevic, Tatjana Damjanovic, Ana Savic-Radojevic, Marija Pljesa-Ercegovac, Vesna Coric, Aleksandra Stefanovic, Jasmina Ivanisevic, Zorana Jelic-Ivanovic, Lana McClements, Nada Dimkovic and Tatjana Simic

Toxins 2019, 11(7), 431; https://doi.org/10.3390/toxins11070431 - 23 Jul 2019

Cited by 26 | Viewed by 4589

Abstract

The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The [...] Read more.

The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival. Full article

(This article belongs to the Special Issue Immune Dysfunction in Uremia)

► Show Figures

Figure 1

14 pages, 730 KiB

Open AccessEditor’s ChoiceArticle

Aflatoxin in Chili Peppers in Nigeria: Extent of Contamination and Control Using Atoxigenic Aspergillus flavus Genotypes as Biocontrol Agents

by Chibundu N. Ezekiel, Alejandro Ortega-Beltran, Eniola O. Oyedeji, Joseph Atehnkeng, Philip Kössler, Folasade Tairu, Irmgard Hoeschle-Zeledon, Petr Karlovsky, Peter J. Cotty and Ranajit Bandyopadhyay

Toxins 2019, 11(7), 429; https://doi.org/10.3390/toxins11070429 - 22 Jul 2019

Cited by 38 | Viewed by 6684

Abstract

Across sub-Saharan Africa, chili peppers are fundamental ingredients of many traditional dishes. However, chili peppers may contain unsafe aflatoxin concentrations produced by Aspergillus section Flavi fungi. Aflatoxin levels were determined in chili peppers from three states in Nigeria. A total of 70 samples [...] Read more.

Across sub-Saharan Africa, chili peppers are fundamental ingredients of many traditional dishes. However, chili peppers may contain unsafe aflatoxin concentrations produced by Aspergillus section Flavi fungi. Aflatoxin levels were determined in chili peppers from three states in Nigeria. A total of 70 samples were collected from farmers’ stores and local markets. Over 25% of the samples contained unsafe aflatoxin concentrations. The chili peppers were associated with both aflatoxin producers and atoxigenic Aspergillus flavus genotypes. Efficacy of an atoxigenic biocontrol product, Aflasafe, registered in Nigeria for use on maize and groundnut, was tested for chili peppers grown in three states. Chili peppers treated with Aflasafe accumulated significantly less aflatoxins than nontreated chili peppers. The results suggest that Aflasafe is a valuable tool for the production of safe chili peppers. Use of Aflasafe in chili peppers could reduce human exposure to aflatoxins and increase chances to commercialize chili peppers in premium local and international markets. This is the first report of the efficacy of any atoxigenic biocontrol product for controlling aflatoxin in a spice crop. Full article

(This article belongs to the Collection Aflatoxins)

► Show Figures

Figure 1

15 pages, 5366 KiB

Open AccessEditor’s ChoiceArticle

Sclerostin as Regulatory Molecule in Vascular Media Calcification and the Bone–Vascular Axis

by Annelies De Maré, Stuart Maudsley, Abdelkrim Azmi, Jhana O. Hendrickx, Britt Opdebeeck, Ellen Neven, Patrick C D’Haese and Anja Verhulst

Toxins 2019, 11(7), 428; https://doi.org/10.3390/toxins11070428 - 21 Jul 2019

Cited by 56 | Viewed by 5303

Abstract

Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce [...] Read more.

Sclerostin is a well-known inhibitor of bone formation that acts on Wnt/β-catenin signaling. This manuscript considers the possible role of sclerostin in vascular calcification, a process that shares many similarities with physiological bone formation. Rats were exposed to a warfarin-containing diet to induce vascular calcification. Vascular smooth muscle cell transdifferentiation, vascular calcification grade, and bone histomorphometry were examined. The presence and/or production of sclerostin was investigated in serum, aorta, and bone. Calcified human aortas were investigated to substantiate clinical relevance. Warfarin-exposed rats developed vascular calcifications in a time-dependent manner which went along with a progressive increase in serum sclerostin levels. Both osteogenic and adipogenic pathways were upregulated in calcifying vascular smooth muscle cells, as well as sclerostin mRNA and protein levels. Evidence for the local vascular action of sclerostin was found both in human and rat calcified aortas. Warfarin exposure led to a mildly decreased bone and mineralized areas. Osseous sclerostin production and bone turnover did not change significantly. This study showed local production of sclerostin in calcified vessels, which may indicate a negative feedback mechanism to prevent further calcification. Furthermore, increased levels of serum sclerostin, probably originating from excessive local production in calcified vessels, may contribute to the linkage between vascular pathology and impaired bone mineralization. Full article

(This article belongs to the Special Issue The Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD))

► Show Figures

Figure 1

15 pages, 2491 KiB

Open AccessEditor’s ChoiceArticle

The Dual α-Amidation System in Scorpion Venom Glands

by Gustavo Delgado-Prudencio, Lourival D. Possani, Baltazar Becerril and Ernesto Ortiz

Toxins 2019, 11(7), 425; https://doi.org/10.3390/toxins11070425 - 20 Jul 2019

Cited by 32 | Viewed by 5357

Abstract

Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved [...] Read more.

Many peptides in scorpion venoms are amidated at their C-termini. This post-translational modification is paramount for the correct biological function of ion channel toxins and antimicrobial peptides, among others. The discovery of canonical amidation sequences in transcriptome-derived scorpion proproteins suggests that a conserved enzymatic α-amidation system must be responsible for this modification of scorpion peptides. A transcriptomic approach was employed to identify sequences putatively encoding enzymes of the α-amidation pathway. A dual enzymatic α-amidation system was found, consisting of the membrane-anchored, bifunctional, peptidylglycine α-amidating monooxygenase (PAM) and its paralogs, soluble monofunctional peptidylglycine α-hydroxylating monooxygenase (PHMm) and peptidyl-α-hydroxyglycine α-amidating lyase (PALm). Independent genes encode these three enzymes. Amino acid residues responsible for ion coordination and enzymatic activity are conserved in these sequences, suggesting that the enzymes are functional. Potential endoproteolytic recognition sites for proprotein convertases in the PAM sequence indicate that PAM-derived soluble isoforms may also be expressed. Sequences potentially encoding proprotein convertases (PC1 and PC2), carboxypeptidase E (CPE), and other enzymes of the α-amidation pathway, were also found, confirming the presence of this pathway in scorpions. Full article

(This article belongs to the Special Issue Identification and Functional Characterization of Novel Venom Components)

► Show Figures

Figure 1

26 pages, 4792 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Listeria monocytogenes Plasmids and Expression Levels of Plasmid-Encoded Genes during Growth under Salt and Acid Stress Conditions

by Patricia Hingston, Thomas Brenner, Lisbeth Truelstrup Hansen and Siyun Wang

Toxins 2019, 11(7), 426; https://doi.org/10.3390/toxins11070426 - 20 Jul 2019

Cited by 36 | Viewed by 6018

Abstract

Listeria monocytogenes strains are known to harbour plasmids that confer resistance to sanitizers, heavy metals, and antibiotics; however, very little research has been conducted into how plasmids may influence L. monocytogenes’ ability to tolerate food-related stresses. To investigate this, a library ( [...] Read more.

Listeria monocytogenes strains are known to harbour plasmids that confer resistance to sanitizers, heavy metals, and antibiotics; however, very little research has been conducted into how plasmids may influence L. monocytogenes’ ability to tolerate food-related stresses. To investigate this, a library (n = 93) of L. monocytogenes plasmid sequences were compared. Plasmid sequences were divided into two groups (G1 and G2) based on a repA phylogeny. Twenty-six unique plasmid types were observed, with 13 belonging to each of the two repA-based groups. G1 plasmids were significantly (p < 0.05) smaller than G2 plasmids but contained a larger diversity of genes. The most prevalent G1 plasmid (57,083 bp) was observed in 26 strains from both Switzerland and Canada and a variety of serotypes. Quantitative PCR (qPCR) revealed a >2-fold induction of plasmid-contained genes encoding an NADH peroxidase, cadmium ATPase, multicopper oxidase, and a ClpL chaperone protein during growth under salt (6% NaCl) and acid conditions (pH 5) and ProW, an osmolyte transporter, under salt stress conditions. No differences in salt and acid tolerance were observed between plasmid-cured and wildtype strains. This work highlights the abundance of specific plasmid types among food-related L. monocytogenes strains, the unique characteristics of G1 and G2 plasmids, and the possible contributions of plasmids to L. monocytogenes tolerance to food-related stresses. Full article

► Show Figures

Figure 1

17 pages, 2747 KiB

Open AccessEditor’s ChoiceArticle

Ciguatera-Causing Dinoflagellate Gambierdiscus spp. (Dinophyceae) in a Subtropical Region of North Atlantic Ocean (Canary Islands): Morphological Characterization and Biogeography

by Isabel Bravo, Francisco Rodriguez, Isabel Ramilo, Pilar Rial and Santiago Fraga

Toxins 2019, 11(7), 423; https://doi.org/10.3390/toxins11070423 - 19 Jul 2019

Cited by 22 | Viewed by 4753

Abstract

Dinoflagellates belonging to the genus Gambierdiscus produce ciguatoxins (CTXs), which are metabolized in fish to more toxic forms and subsequently cause ciguatera fish poisoning (CFP) in humans. Five species of Gambierdiscus have been described from the Canary Islands, where CTXs in fish have [...] Read more.

Dinoflagellates belonging to the genus Gambierdiscus produce ciguatoxins (CTXs), which are metabolized in fish to more toxic forms and subsequently cause ciguatera fish poisoning (CFP) in humans. Five species of Gambierdiscus have been described from the Canary Islands, where CTXs in fish have been reported since 2004. Here we present new data on the distribution of Gambierdiscus species in the Canary archipelago and specifically from two islands, La Palma and La Gomera, where the genus had not been previously reported. Gambierdiscus spp. concentrations were low, with maxima of 88 and 29 cells·g⁻¹ wet weight in samples from La Gomera and La Palma, respectively. Molecular analysis (LSUrRNA gene sequences) revealed differences in the species distribution between the two islands: only G. excentricus was detected at La Palma whereas four species, G. australes, G. caribaeus, G. carolinianus, and G. excentricus, were identified from La Gomera. Morphometric analyses of cultured cells of the five Canary Islands species and of field specimens from La Gomera included cell size and a characterization of three thecal arrangement traits: (1) the shape of the 2′ plate, (2) the position of Po in the anterior suture of the 2′ plate, and (3) the length–width relationship of the 2″″ plate. Despite the wide morphological variability within the culture and field samples, the use of two or more variables allowed the discrimination of two species in the La Gomera samples: G. cf. excentricus and G. cf. silvae. A comparison of the molecular data with the morphologically based classification demonstrated important coincidences, such as the dominance of G. excentricus, but also differences in the species composition of Gambierdiscus, as G. caribaeus was detected in the study area only by using molecular methods. Full article

(This article belongs to the Special Issue Potentially Toxic Benthic Microorganisms in Freshwater and Marine Ecosystems)

► Show Figures

Figure 1

15 pages, 1663 KiB

Open AccessEditor’s ChoiceArticle

Virulence Characteristics and Antimicrobial Resistance Profiles of Shiga Toxin-Producing Escherichia coli Isolates from Humans in South Africa: 2006–2013

by Musafiri Karama, Beniamino T. Cenci-Goga, Mogaugedi Malahlela, Anthony M. Smith, Karen H. Keddy, Saeed El-Ashram, Lawan M. Kabiru and Alan Kalake

Toxins 2019, 11(7), 424; https://doi.org/10.3390/toxins11070424 - 19 Jul 2019

Cited by 27 | Viewed by 4871

Abstract

Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC [...] Read more.

Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC O26:H11 (24%) was the most frequent serotype associated with human disease, followed by O111:H8 (16%), O157:H7 (13%) and O117:H7 (13%). The majority of isolates were positive for key virulence-associated genes including stx1 (84%), eaeA (61%), ehxA (68.4%) and espP (55%), but lacked stx2 (29%), katP (42%), etpD (16%), saa (16%) and subA (3%). stx2 positive isolates carried stx2c (26%) and/or stx2d (26%) subtypes. All pathogenicity island encoded virulence marker genes were detected in all (100%) isolates except nleA (47%), nleC (84%) and nleD (76%). Multidrug resistance was observed in 89% of isolates. PFGE revealed 34 profiles with eight distinct clusters that shared ≥80% intra-serotype similarity, regardless of the year of isolation. In conclusion, STEC isolates that were implicated in human disease between 2006 and 2013 in South Africa were mainly non-O157 strains which possessed virulence genes and markers commonly associated with STEC strains that have been incriminated in mild to severe human disease worldwide. Improved STEC monitoring and surveillance programs are needed in South Africa to control and prevent STEC disease in humans. Full article

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

► Show Figures

Figure 1

20 pages, 2175 KiB

Open AccessEditor’s ChoiceArticle

Daphnia magna Exudates Impact Physiological and Metabolic Changes in Microcystis aeruginosa

by Gorenka Bojadzija Savic, Christine Edwards, Enora Briand, Linda Lawton, Claudia Wiegand and Myriam Bormans

Toxins 2019, 11(7), 421; https://doi.org/10.3390/toxins11070421 - 19 Jul 2019

Cited by 10 | Viewed by 5413

Abstract

While the intracellular function of many toxic and bioactive cyanobacterial metabolites is not yet known, microcystins have been suggested to have a protective role in the cyanobacterial metabolism, giving advantage to toxic over nontoxic strains under stress conditions. The zooplankton grazer Daphnia reduce [...] Read more.

While the intracellular function of many toxic and bioactive cyanobacterial metabolites is not yet known, microcystins have been suggested to have a protective role in the cyanobacterial metabolism, giving advantage to toxic over nontoxic strains under stress conditions. The zooplankton grazer Daphnia reduce cyanobacterial dominance until a certain density, which may be supported by Daphnia exudates, affecting the cyanobacterial physiological state and metabolites’ production. Therefore, we hypothesized that D. magna spent medium will impact the production of cyanobacterial bioactive metabolites and affect cyanobacterial photosynthetic activity in the nontoxic, but not the toxic strain. Microcystin (MC-LR and des-MC-LR) producing M. aeruginosa PCC7806 and its non-microcystin producing mutant were exposed to spent media of different D. magna densities and culture durations. D. magna spent medium of the highest density (200/L) cultivated for the shortest time (24 h) provoked the strongest effect. D.magna spent medium negatively impacted the photosynthetic activity of M. aeruginosa PCC7806, as well as the dynamics of intracellular and extracellular cyanobacterial metabolites, while its mutant was unaffected. In the presence of Daphnia medium, microcystin does not appear to have a protective role for the strain. On the contrary, extracellular cyanopeptolin A increased in M. aeruginosa PCC7806 although the potential anti-grazing role of this compound would require further studies. Full article

(This article belongs to the Special Issue Environmental Drivers of Algal and Cyanobacterial Toxin Dynamics)

► Show Figures

Figure 1

20 pages, 8235 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis

by Nicholas J. Youngman, Jordan Debono, James S. Dobson, Christina N. Zdenek, Richard J. Harris, Bianca op den Brouw, Francisco C. P. Coimbra, Arno Naude, Kristian Coster, Eric Sundman, Ralph Braun, Iwan Hendrikx and Bryan G. Fry

Toxins 2019, 11(7), 422; https://doi.org/10.3390/toxins11070422 - 19 Jul 2019

Cited by 32 | Viewed by 7353

Abstract

The genus Bitis comprises 18 species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor [...] Read more.

The genus Bitis comprises 18 species that inhabit Africa and the Arabian Peninsula. They are responsible for a significant proportion of snakebites in the region. The venoms of the two independent lineages of giant Bitis (B. arietans and again in the common ancestor of the clade consisting of B. gabonica, B. nasicornis, B. parviocula and B. rhinoceros) induce an array of debilitating effects including anticoagulation, hemorrhagic shock and cytotoxicity, whilst the dwarf species B. atropos is known to have strong neurotoxic effects. However, the venom effects of the other species within the genus have not been explored in detail. A series of coagulation assays were implemented to assess the coagulotoxic venom effects of fourteen species within the genus. This study identified procoagulant venom as the ancestral condition, retained only by the basal dwarf species B. worthingtoni, suggesting anticoagulant venom is a derived trait within the Bitis genus and has been secondarily amplified on at least four occasions. A wide range of anticoagulant mechanisms were identified, such as pseudo-procoagulant and destructive activities upon fibrinogen in both giant and dwarf Bitis and the action of inhibiting the prothrombinase complex, which is present in a clade of dwarf Bitis. Antivenom studies revealed that while the procoagulant effects of B. worthingtoni were poorly neutralized, and thus a cause for concern, the differential mechanisms of anticoagulation in other species were all well neutralized. Thus, this study concludes there is a wide range of coagulotoxic mechanisms which have evolved within the Bitis genus and that clinical management strategies are limited for the procoagulant effects of B. worthingtoni, but that anticoagulant effects of other species are readily treated by the South African polyvalent antivenom. These results therefore have direct, real-work implications for the treatment of envenomed patients. Full article

(This article belongs to the Special Issue Medically Relevant Snake Toxins, Current Antivenoms and the Development of Next-Generation Antivenoms)

► Show Figures

Figure 1

28 pages, 3095 KiB

Open AccessEditor’s ChoiceReview

Rapid Detection of Botulinum Neurotoxins—A Review

by Robert J. Hobbs, Carol A. Thomas, Jennifer Halliwell and Christopher D. Gwenin

Toxins 2019, 11(7), 418; https://doi.org/10.3390/toxins11070418 - 17 Jul 2019

Cited by 39 | Viewed by 11340

Abstract

A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to [...] Read more.

A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent. Full article

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

► Show Figures

Figure 1

19 pages, 298 KiB

Open AccessEditor’s ChoiceReview

Assays for Determining Pertussis Toxin Activity in Acellular Pertussis Vaccines

by Kevin Markey, Catpagavalli Asokanathan and Ian Feavers

Toxins 2019, 11(7), 417; https://doi.org/10.3390/toxins11070417 - 17 Jul 2019

Cited by 15 | Viewed by 4190

Abstract

Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This [...] Read more.

Whooping cough is caused by the bacterium Bordetella pertussis. There are currently two types of vaccines that can prevent the disease; whole cell vaccines (WCV) and acellular vaccines (ACV). The main virulence factor produced by the organism is pertussis toxin (PTx). This toxin is responsible for many physiological effects on the host, but it is also immunogenic and in its detoxified form is the main component of all ACVs. In producing toxoid for vaccines, it is vital to achieve a balance between sufficiently detoxifying PTx to render it safe while maintaining enough molecular structure that it retains its protective immunogenicity. To ensure that the first part of this balancing act has been successfully achieved, assays are required to accurately measure residual PTx activity in ACV products accurately. Quality control assays are also required to ensure that the detoxification procedures are robust and stable. This manuscript reviews the methods that have been used to achieve this aim, or may have the potential to replace them, and highlights their continuing requirement as vaccines that induce a longer lasting immunity are developed to prevent the re-occurrence of outbreaks that have been observed recently. Full article

(This article belongs to the Special Issue Pertussis Toxin)

13 pages, 5247 KiB

Open AccessEditor’s ChoiceArticle

Reduction of Deoxynivalenol in Wheat with Superheated Steam and Its Effects on Wheat Quality

by Yuanxiao Liu, Mengmeng Li, Ke Bian, Erqi Guan, Yuanfang Liu and Ying Lu

Toxins 2019, 11(7), 414; https://doi.org/10.3390/toxins11070414 - 16 Jul 2019

Cited by 32 | Viewed by 3907

Abstract

Deoxynivalenol (DON) is the most commonly found mycotoxin in scabbed wheat. In order to reduce the DON concentration in scabbed wheat with superheated steam (SS) and explore the feasibility to use the processed wheat as crisp biscuit materials, wheat kernels were treated with [...] Read more.

Deoxynivalenol (DON) is the most commonly found mycotoxin in scabbed wheat. In order to reduce the DON concentration in scabbed wheat with superheated steam (SS) and explore the feasibility to use the processed wheat as crisp biscuit materials, wheat kernels were treated with SS to study the effects of SS processing on DON concentration and the quality of wheat. Furthermore, the wheat treated with SS were used to make crisp biscuits and the texture qualities of biscuits were measured. The results showed that DON in wheat kernels could be reduced by SS effectively. Besides, the reduction rate raised significantly with the increase of steam temperature and processing time and it was also affected significantly by steam velocity. The reduction rate in wheat kernels and wheat flour could reach 77.4% and 60.5% respectively. In addition, SS processing might lead to partial denaturation of protein and partial gelatinization of starch, thus affecting the rheological properties of dough and pasting properties of wheat flour. Furthermore, the qualities of crisp biscuits were improved at certain conditions of SS processing. Full article

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

► Show Figures

Graphical abstract

16 pages, 1778 KiB

Open AccessEditor’s ChoiceReview

The ADP-Ribosylating Toxins of Salmonella

by Rachel A. Cheng and Martin Wiedmann

Toxins 2019, 11(7), 416; https://doi.org/10.3390/toxins11070416 - 16 Jul 2019

Cited by 16 | Viewed by 7994

Abstract

A number of pathogenic bacteria utilize toxins to mediate disease in a susceptible host. The foodborne pathogen Salmonella is one of the most important and well-studied bacterial pathogens. Recently, whole genome sequence characterizations revealed the presence of multiple novel ADP-ribosylating toxins encoded by [...] Read more.

A number of pathogenic bacteria utilize toxins to mediate disease in a susceptible host. The foodborne pathogen Salmonella is one of the most important and well-studied bacterial pathogens. Recently, whole genome sequence characterizations revealed the presence of multiple novel ADP-ribosylating toxins encoded by a variety of Salmonella serovars. In this review, we discuss both the classical (SpvB) and novel (typhoid toxin, ArtAB, and SboC/SeoC) ADP-ribosylating toxins of Salmonella, including the structure and function of these toxins and our current understanding of their contributions to virulence. Full article

(This article belongs to the Special Issue ADP-Ribosylating Toxin)

► Show Figures

Figure 1

17 pages, 2322 KiB

Open AccessEditor’s ChoiceReview

Understanding Mycotoxin Contamination Across the Food Chain in Brazil: Challenges and Opportunities

by Marta H. Taniwaki, John I. Pitt, Marina V. Copetti, Aldir A. Teixeira and Beatriz T. Iamanaka

Toxins 2019, 11(7), 411; https://doi.org/10.3390/toxins11070411 - 15 Jul 2019

Cited by 40 | Viewed by 5882

Abstract

Brazil is one of the largest food producers and exporters in the world. In the late 20th century, the European Union program for the harmonization of regulations for contaminants in food, including mycotoxins, led to the examination of mycotoxin contamination in foods at [...] Read more.

Brazil is one of the largest food producers and exporters in the world. In the late 20th century, the European Union program for the harmonization of regulations for contaminants in food, including mycotoxins, led to the examination of mycotoxin contamination in foods at a global level. The problem of the rejection of food by the European Union and other countries became a Brazilian national priority because of economic and food safety aspects. Ochratoxin A in coffee and cocoa and aflatoxins in Brazil nuts are examples of the impact of technical trade barriers on Brazilian foods. To overcome these threats, several strategies were undertaken by Brazilian and international organizations. In this context, the Codex Commission on Food Contaminants (CCCF) has emerged as a forum to discuss with more transparency issues related to mycotoxins, focusing on establishing maximum levels and codes of practices for some commodities and mycotoxins to ensure fair trade and food safety. Our experience in investigating and understanding mycotoxin contamination across the food chains in Brazil has contributed nationally and internationally to providing some answers to these issues. Full article

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

► Show Figures

Graphical abstract

11 pages, 567 KiB

Open AccessEditor’s ChoicePerspective

Aflatoxin Binders in Foods for Human Consumption—Can This be Promoted Safely and Ethically?

by Sara Ahlberg, Delia Randolph, Sheila Okoth and Johanna Lindahl

Toxins 2019, 11(7), 410; https://doi.org/10.3390/toxins11070410 - 14 Jul 2019

Cited by 18 | Viewed by 5802

Abstract

Aflatoxins continue to be a food safety problem globally, especially in developing regions. A significant amount of effort and resources have been invested in an attempt to control aflatoxins. However, these efforts have not substantially decreased the prevalence nor the dietary exposure to [...] Read more.

Aflatoxins continue to be a food safety problem globally, especially in developing regions. A significant amount of effort and resources have been invested in an attempt to control aflatoxins. However, these efforts have not substantially decreased the prevalence nor the dietary exposure to aflatoxins in developing countries. One approach to aflatoxin control is the use of binding agents in foods, and lactic acid bacteria (LAB) have been studied extensively for this purpose. However, when assessing the results comprehensively and reviewing the practicality and ethics of use, risks are evident, and concerns arise. In conclusion, our review suggests that there are too many issues with using LAB for aflatoxin binding for it to be safely promoted. Arguably, using binders in human food might even worsen food safety in the longer term. Full article

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

► Show Figures

Figure 1

13 pages, 12341 KiB

Open AccessEditor’s ChoiceArticle

Prodigiosin Promotes Nrf2 Activation to Inhibit Oxidative Stress Induced by Microcystin-LR in HepG2 Cells

by Jihua Chen, Yuji Li, Fuqiang Liu, De-Xing Hou, Jingjing Xu, Xinying Zhao, Fei Yang and Xiangling Feng

Toxins 2019, 11(7), 403; https://doi.org/10.3390/toxins11070403 - 12 Jul 2019

Cited by 25 | Viewed by 4413

Abstract

Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR [...] Read more.

Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future. Full article

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

► Show Figures

Figure 1

13 pages, 2774 KiB

Open AccessEditor’s ChoiceArticle

The Activity of Isoquinoline Alkaloids and Extracts from Chelidonium majus against Pathogenic Bacteria and Candida sp.

by Sylwia Zielińska, Magdalena Wójciak-Kosior, Magdalena Dziągwa-Becker, Michał Gleńsk, Ireneusz Sowa, Karol Fijałkowski, Danuta Rurańska-Smutnicka, Adam Matkowski and Adam Junka

Toxins 2019, 11(7), 406; https://doi.org/10.3390/toxins11070406 - 12 Jul 2019

Cited by 55 | Viewed by 5247

Abstract

Chelidonium majus (Papaveraceae) extracts exhibit antimicrobial activity due to the complex alkaloid composition. The aim of the research was to evaluate the antimicrobial potential of extracts from wild plants and in vitro cultures, as well as seven major individual alkaloids. Plant [...] Read more.

Chelidonium majus (Papaveraceae) extracts exhibit antimicrobial activity due to the complex alkaloid composition. The aim of the research was to evaluate the antimicrobial potential of extracts from wild plants and in vitro cultures, as well as seven major individual alkaloids. Plant material derived from different natural habitats and in vitro cultures was used for the phytochemical analysis and antimicrobial tests. The composition of alkaloids was analyzed using chromatographic techniques (HPLC with DAD detection). The results have shown that roots contained higher number and amounts of alkaloids in comparison to aerial parts. All tested plant extracts manifested antimicrobial activity, related to different chemical structures of the alkaloids. Root extract used at 31.25–62.5 mg/L strongly reduced bacterial biomass. From the seven individually tested alkaloids, chelerythrine was the most effective against P. aeruginosa (MIC at 1.9 mg/L), while sanguinarine against S. aureus (MIC at 1.9 mg/L). Strong antifungal activity was observed against C. albicans when chelerythrine, chelidonine, and aerial parts extract were used. The experiments with plant extracts, individually tested alkaloids, and variable combinations of the latter allowed for a deeper insight into the potential mechanisms affecting the activity of this group of compounds. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

► Show Figures

Graphical abstract

8 pages, 1943 KiB

Open AccessEditor’s ChoiceArticle

Toxic Flatworm Egg Plates Serve as a Possible Source of Tetrodotoxin for Pufferfish

by Taiki Okabe, Hikaru Oyama, Maho Kashitani, Yuta Ishimaru, Rei Suo, Haruo Sugita and Shiro Itoi

Toxins 2019, 11(7), 402; https://doi.org/10.3390/toxins11070402 - 11 Jul 2019

Cited by 32 | Viewed by 10046

Abstract

The pufferfish Takifugu niphobles (at present Takifugu alboplumbeus) possesses highly concentrated tetrodotoxin (TTX), an extremely potent neurotoxin that provides effective protection from predators, at least at the larval stages. However, the source of the toxin has remained unclear. Recently, DNA from the [...] Read more.

The pufferfish Takifugu niphobles (at present Takifugu alboplumbeus) possesses highly concentrated tetrodotoxin (TTX), an extremely potent neurotoxin that provides effective protection from predators, at least at the larval stages. However, the source of the toxin has remained unclear. Recently, DNA from the toxic flatworm Planocera multitentaculata was detected in the intestinal contents of juveniles and young of the pufferfish, suggesting that the flatworm contributes to its toxification at various stages of its life. In this study, we describe the behavior of the pufferfish in the intertidal zone that appears to contribute to its toxification before and during its spawning period: pufferfish were found to aggregate and ingest flatworm egg plates by scraping them off the surface of rocks. DNA analysis based on 28S rRNA and cytochrome c oxidase subunit I (COI) genes identified the egg plates as those of P. multitentaculata. Liquid chromatography with tandem mass spectrometry analysis revealed that the egg plates contain highly concentrated TTX. The feeding behavior of the pufferfish on the flatworm egg plates was also observed in the aquarium. These results suggest that pufferfish feed on the flatworm egg plate, which enables them to acquire toxicity themselves while providing their offspring with the protective shield of TTX. Full article

(This article belongs to the Special Issue Isolation and Characterization of Marine Toxins)

► Show Figures

Graphical abstract

14 pages, 27246 KiB

Open AccessEditor’s ChoiceArticle

Tannic Acid Induces the Mitochondrial Pathway of Apoptosis and S Phase Arrest in Porcine Intestinal IPEC-J2 Cells

by Ji Wang, Haisi Xiao, Yuanyuan Zhu, Shuiping Liu, Zhihang Yuan, Jing Wu and Lixin Wen

Toxins 2019, 11(7), 397; https://doi.org/10.3390/toxins11070397 - 9 Jul 2019

Cited by 14 | Viewed by 4114

Abstract

The presence of tannic acid (TA), which is widely distributed in plants, limits the utilization of non-grain feed. Illustrating the toxicity mechanism of TA in animals is important for preventing poisoning and for clinical development of TA. The aim of the present study [...] Read more.

The presence of tannic acid (TA), which is widely distributed in plants, limits the utilization of non-grain feed. Illustrating the toxicity mechanism of TA in animals is important for preventing poisoning and for clinical development of TA. The aim of the present study was to evaluate the toxic effects and possible action mechanism of TA in porcine intestinal IPEC-J2 cells, as well as cell proliferation, apoptosis, and cell cycle. We investigated the toxic effects of TA in IPEC-J2 cells combining the analysis of TA-induced apoptotic responses and effect on the cell cycle. The results revealed that TA is highly toxic to IPEC-J2 cells. The stress-inducible factors reactive oxygen species, malondialdehyde, and 8-hydroxy-2′-deoxyguanosine were increased in response to TA. Furthermore, TA suppressed mitochondrial membrane potential, reduced adenosine triphosphate production, and adversely affected B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, caspase-9, caspase-3, cytochrome c, cyclin A, cyclin-dependent kinases, ataxia-telangiectasia mutated, and P53 expression in a dose-dependent manner. We suggest that TA induces the mitochondrial pathway of apoptosis and S phase arrest in IPEC-J2 cells. Full article

(This article belongs to the Section Plant Toxins)

► Show Figures

Graphical abstract

19 pages, 5199 KiB

Open AccessEditor’s ChoiceArticle

Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats

by Tarana Arman, Katherine D. Lynch, Michelle L. Montonye, Michael Goedken and John D. Clarke

Toxins 2019, 11(7), 398; https://doi.org/10.3390/toxins11070398 - 9 Jul 2019

Cited by 25 | Viewed by 4160

Abstract

Microcystin-LR (MCLR) is a hepatotoxic cyanotoxin reported to cause a phenotype similar to nonalcoholic steatohepatitis (NASH). NASH is a common progressive liver disease that advances in severity due to exogenous stressors such as poor diet and toxicant exposure. Our objective was to determine [...] Read more.

Microcystin-LR (MCLR) is a hepatotoxic cyanotoxin reported to cause a phenotype similar to nonalcoholic steatohepatitis (NASH). NASH is a common progressive liver disease that advances in severity due to exogenous stressors such as poor diet and toxicant exposure. Our objective was to determine how sub-chronic MCLR toxicity affects preexisting diet-induced NASH. Sprague-Dawley rats were fed one of three diets for 10 weeks: control, methionine and choline deficient (MCD), or high fat/high cholesterol (HFHC). After six weeks of diet, animals received vehicle, 10 µg/kg, or 30 µg/kg MCLR via intraperitoneal injection every other day for the final 4 weeks. Incidence and severity scoring of histopathology endpoints suggested that MCLR toxicity drove NASH to a less fatty and more fibrotic state. In general, expression of genes involved in de novo lipogenesis and fatty acid esterification were altered in favor of decreased steatosis. The higher MCLR dose increased expression of genes involved in fibrosis and inflammation in the control and HFHC groups. These data suggest MCLR toxicity in the context of preexisting NASH may drive the liver to a more severe phenotype that resembles burnt-out NASH. Full article

► Show Figures

Figure 1

10 pages, 2061 KiB

Open AccessEditor’s ChoiceArticle

Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats

by Seunghwan Choi, Hyeon Kyeong Chae, Ho Heo, Dae-Hyun Hahm, Woojin Kim and Sun Kwang Kim

Toxins 2019, 11(7), 396; https://doi.org/10.3390/toxins11070396 - 8 Jul 2019

Cited by 25 | Viewed by 4369

Abstract

Oxaliplatin is a chemotherapeutic agent used for metastatic colon and other advanced cancers. Most common side effect of oxaliplatin is peripheral neuropathy, manifested in mechanical and cold allodynia. Although the analgesic effect of bee venom has been proven to be effective against oxaliplatin-induced [...] Read more.

Oxaliplatin is a chemotherapeutic agent used for metastatic colon and other advanced cancers. Most common side effect of oxaliplatin is peripheral neuropathy, manifested in mechanical and cold allodynia. Although the analgesic effect of bee venom has been proven to be effective against oxaliplatin-induced peripheral neuropathy, the effect of its major component; melittin has not been studied yet. Thus, in this study, we investigated whether melittin has an analgesic effect on oxaliplatin-induced allodynia. Intraperitoneal single injection of oxaliplatin (6 mg/kg) induced mechanical and cold allodynia, resulting in increased withdrawal behavior in response to von Frey filaments and acetone drop on hind paw. Subcutaneous melittin injection on acupoint ST36 (0.5 mg/kg) alleviated oxaliplatin-induced mechanical and cold allodynia. In electrophysiological study, using spinal in vivo extracellular recording, it was shown that oxaliplatin-induced hyperexcitation of spinal wide dynamic range neurons in response to peripheral stimuli, and melittin administration inhibited this neuronal activity. In behavioral assessment, analgesic effect of melittin was blocked by intrathecal α1- and α2- adrenergic receptor antagonists administration. Based on these results, we suggest that melittin could be used as an analgesic on oxaliplatin-induced peripheral neuropathy, and that its effect is mediated by activating the spinal α1- and α2-adrenergic receptors. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

► Show Figures

Figure 1

16 pages, 1891 KiB

Open AccessEditor’s ChoiceArticle

LC–MS/MS Analysis of the Emerging Toxin Pinnatoxin-G and High Levels of Esterified OA Group Toxins in Galician Commercial Mussels

by Paz Otero, Natalia Miguéns, Inés Rodríguez and Luis M. Botana

Toxins 2019, 11(7), 394; https://doi.org/10.3390/toxins11070394 - 5 Jul 2019

Cited by 30 | Viewed by 4339

Abstract

The occurrence of marine harmful algae is increasing worldwide and, therefore, the accumulation of lipophilic marine toxins from harmful phytoplankton represents a food safety threat in the shellfish industry. Galicia, which is a commercially important EU producer of edible bivalve mollusk have been [...] Read more.

The occurrence of marine harmful algae is increasing worldwide and, therefore, the accumulation of lipophilic marine toxins from harmful phytoplankton represents a food safety threat in the shellfish industry. Galicia, which is a commercially important EU producer of edible bivalve mollusk have been subjected to recurring cases of mussel farm closures, in the last decades. This work aimed to study the toxic profile of commercial mussels (Mytilus galloprovincialis) in order to establish a potential risk when ingested. For this, a total of 41 samples of mussels farmed in 3 Rías (Ares-Sada, Arousa, and Pontevedra) and purchased in 5 local markets were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS). Chromatograms showed the presence of okadaic acid (OA), dinophysistoxin-2 (DTX-2), pectenotoxin-2 (PTX-2), azaspiracid-2 (AZA-2), and the emerging toxins 13-desmethyl spirolide C (SPX-13), and pinnatoxin-G (PnTX-G). Quantification of each toxin was determined using their own standard calibration in the range 0.1%–50 ng/mL (R2 > 0.99) and by considering the toxin recovery (62–110%) and the matrix correction (33–211%). Data showed that OA and DTX-2 (especially in the form of esters) are the main risk in Galician mollusks, which was detected in 38 samples (93%) and 3 of them exceeded the legal limit (160 µg/kg), followed by SPX-13 that was detected in 19 samples (46%) in quantities of up to 28.9 µg/kg. Analysis from PTX-2, AZA-2, and PnTX-G showed smaller amounts. Fifteen samples (37%) were positive for PTX-2 (0.7–2.9 µg/kg), 12 samples (29%) for AZA-2 (0.1–1.8 µg/kg), and PnTX-G was detected in 5 mussel samples (12%) (0.4 µg/kg–0.9 µg/kg). This is the first time Galician mollusk was contaminated with PnTX-G. Despite results indicating that this toxin was not a potential risk through the mussel ingestion, it should be considered in the shellfish safety monitoring programs through the LC–MS/MS methods. Full article

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

► Show Figures

Graphical abstract

17 pages, 1132 KiB

Open AccessEditor’s ChoiceArticle

A Bifunctional Adsorber Particle for the Removal of Hydrophobic Uremic Toxins from Whole Blood of Renal Failure Patients

by Marieke Sternkopf, Sven Thoröe-Boveleth, Tobias Beck, Kirsten Oleschko, Ansgar Erlenkötter, Ulrich Tschulena, Sonja Steppan, Thimoteus Speer, Claudia Goettsch, Vera Jankowski, Joachim Jankowski, Heidi Noels and The European Uremic Toxin Work Group-EUTox

Toxins 2019, 11(7), 389; https://doi.org/10.3390/toxins11070389 - 3 Jul 2019

Cited by 18 | Viewed by 4861

Abstract

Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques [...] Read more.

Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques may be an appropriate alternative to increase hydrophobic uremic toxin removal. We developed an extracorporeal, whole-blood bifunctional adsorber particle consisting of a porous, activated charcoal core with a hydrophilic polyvinylpyrrolidone surface coating. The adsorption capacity was quantified using analytical chromatography after perfusion of the particles with an albumin solution or blood, each containing mixtures of hydrophobic uremic toxins. A time-dependent increase in hydrophobic uremic toxin adsorption was depicted and all toxins showed a high binding affinity to the adsorber particles. Further, the particle showed a sufficient hemocompatibility without significant effects on complement component 5a, thrombin-antithrombin III complex, or thrombocyte concentration in blood in vitro, although leukocyte counts were slightly reduced. In conclusion, the bifunctional adsorber particle with cross-linked polyvinylpyrrolidone coating showed a high adsorption capacity without adverse effects on hemocompatibility in vitro. Thus, it may be an interesting candidate for further in vivo studies with the aim to increase the efficiency of conventional dialysis techniques. Full article

(This article belongs to the Section Uremic Toxins)

► Show Figures

Graphical abstract

10 pages, 1519 KiB

Open AccessEditor’s ChoiceArticle

Fumonisin B₁ Induces Oxidative Stress and Breaks Barrier Functions in Pig Iliac Endothelium Cells

by Qiaoling Yuan, Yancheng Jiang, Ying Fan, Yingfeng Ma, Hongyu Lei and Jianming Su

Toxins 2019, 11(7), 387; https://doi.org/10.3390/toxins11070387 - 2 Jul 2019

Cited by 26 | Viewed by 3493

Abstract

Fumonisins (Fums) are types of mycotoxin that widely contaminante feed material crops, and can trigger potential biological toxicities to humans and various animals. However, the toxicity of Fums on porcine blood vessels has not been fully explored. Fumonisin B₁ (FB₁) [...] Read more.

Fumonisins (Fums) are types of mycotoxin that widely contaminante feed material crops, and can trigger potential biological toxicities to humans and various animals. However, the toxicity of Fums on porcine blood vessels has not been fully explored. Fumonisin B₁ (FB₁) is the main component of Fums. Therefore, the aim of this study was to explore the effects of FB₁ on the oxidative stress and tight junctions of the pig iliac endothelial cells (PIECs) in vitro. The results showed that FB₁ reduced the viability of PIECs, increased the contents of lipid peroxidation product malondialdehyde (MDA), decreased the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thioredoxin reductase (TrxR), and decreased the level of glutathione (GSH). In addition, the barrier functions were destroyed, along with the down-regulations on Claudin 1, Occludin and ZO-1 and the increase of paracellular permeability. Thus, this research indicates that FB₁ facilitates oxidative stress and breaks barrier functions to damage pig iliac endothelium cells. Full article

► Show Figures

Figure 1

13 pages, 1600 KiB

Open AccessEditor’s ChoiceArticle

Fluorescence Polarization Immunoassay for the Determination of T-2 and HT-2 Toxins and Their Glucosides in Wheat

by Vincenzo Lippolis, Anna C. R. Porricelli, Erminia Mancini, Biancamaria Ciasca, Veronica M. T. Lattanzio, Annalisa De Girolamo, Chris M. Maragos, Susan McCormick, Peiwu Li, Antonio F. Logrieco and Michelangelo Pascale

Toxins 2019, 11(7), 380; https://doi.org/10.3390/toxins11070380 - 1 Jul 2019

Cited by 22 | Viewed by 4132

Abstract

T-2 and HT-2 toxins and their main modified forms (T-2 glucoside and HT-2 glucoside) may co-occur in cereals and cereal-based products. A fluorescence polarization immunoassay (FPIA) was developed for the simultaneous determination of T-2 toxin, HT-2 toxin and relevant glucosides, expressed as sum. [...] Read more.

T-2 and HT-2 toxins and their main modified forms (T-2 glucoside and HT-2 glucoside) may co-occur in cereals and cereal-based products. A fluorescence polarization immunoassay (FPIA) was developed for the simultaneous determination of T-2 toxin, HT-2 toxin and relevant glucosides, expressed as sum. The developed FPIA, using a HT-2-specific antibody, showed high sensitivity (IC₅₀ = 2.0 ng/mL) and high cross-reactivity (100% for T-2 toxin and 80% for T-2 and HT-2 glucosides). The FPIA has been used to develop two rapid and easy-to-use methods using two different extraction protocols, based on the use of organic (methanol/water, 90:10, v/v) and non-organic (water) solvents, for the determination of these toxins in wheat. The two proposed methods showed analytical performances in terms of sensitivity (LOD 10 µg/kg) recovery (92–97%) and precision (relative standard deviations ≤13%), fulfilling the criteria for acceptability of an analytical method for the quantitative determination of T-2 and HT-2 toxins established by the European Union. Furthermore, the methods were then validated in accordance with the harmonized guidelines for the validation of screening methods included in the Regulation (EU) No. 519/2014. The satisfactory analytical performances, in terms of intermediate precision (≤25%), cut-off level (80 and 96 µg/kg for the two methods) and rate of false positives (<0.1%) confirmed the applicability of the proposed methods as screening method for assessing the content of these toxins in wheat at the EU indicative levels reported for T-2 and HT-2 toxins. Full article

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

► Show Figures

Graphical abstract

25 pages, 5336 KiB

Open AccessEditor’s ChoiceArticle

Identification and Evaluations of Novel Insecticidal Proteins from Plants of the Class Polypodiopsida for Crop Protection against Key Lepidopteran Pests

by Lu Liu, Eric Schepers, Amy Lum, Janet Rice, Nasser Yalpani, Ryan Gerber, Nuria Jiménez-Juárez, Fikru Haile, Alejandra Pascual, Jennifer Barry, Xiuli Qi, Adane Kassa, Matthew J. Heckert, Weiping Xie, Changkui Ding, Jarred Oral, Minh Nguyen, James Le, Lisa Procyk, Scott H. Diehn, Virginia C. Crane, Howard Damude, Carol Pilcher, Russ Booth, Lu Liu, Genhai Zhu, Timothy M. Nowatzki, Mark E. Nelson, Albert L. Lu and Gusui Wu Show full author list Hide full author list

Toxins 2019, 11(7), 383; https://doi.org/10.3390/toxins11070383 - 1 Jul 2019

Cited by 18 | Viewed by 9104

Abstract

Various lepidopteran insects are responsible for major crop losses worldwide. Although crop plant varieties developed to express Bacillus thuringiensis (Bt) proteins are effective at controlling damage from key lepidopteran pests, some insect populations have evolved to be insensitive to certain Bt proteins. Here, [...] Read more.

Various lepidopteran insects are responsible for major crop losses worldwide. Although crop plant varieties developed to express Bacillus thuringiensis (Bt) proteins are effective at controlling damage from key lepidopteran pests, some insect populations have evolved to be insensitive to certain Bt proteins. Here, we report the discovery of a family of homologous proteins, two of which we have designated IPD083Aa and IPD083Cb, which are from Adiantum spp. Both proteins share no known peptide domains, sequence motifs, or signatures with other proteins. Transgenic soybean or corn plants expressing either IPD083Aa or IPD083Cb, respectively, show protection from feeding damage by several key pests under field conditions. The results from comparative studies with major Bt proteins currently deployed in transgenic crops indicate that the IPD083 proteins function by binding to different target sites. These results indicate that IPD083Aa and IPD083Cb can serve as alternatives to traditional Bt-based insect control traits with potential to counter insect resistance to Bt proteins. Full article

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

► Show Figures

Graphical abstract

13 pages, 1245 KiB

Open AccessEditor’s ChoiceArticle

Pig Urinary Concentration of Mycotoxins and Metabolites Reflects Regional Differences, Mycotoxin Intake and Feed Contaminations

by Lucia Gambacorta, Monica Olsen and Michele Solfrizzo

Toxins 2019, 11(7), 378; https://doi.org/10.3390/toxins11070378 - 30 Jun 2019

Cited by 20 | Viewed by 4010

Abstract

The determination of mycotoxin and metabolite concentrations in human and animal urine is currently used for risk assessment and mycotoxin intake measurement. In this study, pig urine (n = 195) was collected at slaughterhouses in 2012 by the Swedish National Food Agency [...] Read more.

The determination of mycotoxin and metabolite concentrations in human and animal urine is currently used for risk assessment and mycotoxin intake measurement. In this study, pig urine (n = 195) was collected at slaughterhouses in 2012 by the Swedish National Food Agency in three counties representing East, South and West regions of Sweden. Urinary concentrations of four mycotoxins, (deoxynivalenol (DON), zearalenone (ZEA), fumonisin B₁ (FB₁), and ochratoxin A (OTA)), and four key metabolites, (deepoxy-deoxynivalenol (DOM-1), aflatoxin M₁ (AFM₁, biomarker of AFB₁), α-zearalenol (α-ZOL), and β-zearalenol (β-ZOL)) were identified and measured by UPLC-MS/MS. Statistically significant regional differences were detected for both total DON (DON + DOM-1) and total ZEA (ZEA + α-ZOL + β-ZOL) concentrations in pig urine from the three regions. These regional differences were in good agreement with the occurrence of Fusarium graminearum mycotoxins (DON + ZEA) in cereal grains harvested in 2011 in Sweden. There were no statistically significant differences in FB₁, AFM₁ and OTA urinary concentrations in pigs from the three regions. The overall incidence of positive samples was high for total ZEA (99–100%), total DON (96–100%) and OTA (85–95%), medium for FB₁ (30–61%) and low for AFM₁ (0–13%) in the three regions. Urinary mycotoxin biomarker concentrations were used to estimate mycotoxin intake and the level of mycotoxins in feeds consumed by the monitored pigs. The back-calculated levels of mycotoxins in feeds were low with the exception of seven samples that were higher the European limits. Full article

(This article belongs to the Special Issue Mycotoxin Contamination Management Tools and Efficient Strategies in Feed Industry)

► Show Figures

Figure 1

11 pages, 1639 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin

by Yaqun Fang, Xiaoqin He, Pengcheng Zhang, Chuanbin Shen, James Mwangi, Cheng Xu, Guoxiang Mo, Ren Lai and Zhiye Zhang

Toxins 2019, 11(7), 379; https://doi.org/10.3390/toxins11070379 - 30 Jun 2019

Cited by 28 | Viewed by 4446

Abstract

Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed [...] Read more.

Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stage Plasmodium falciparum (P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against Plasmodium berghei (P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during P. berghei infection. Furthermore, by employing inhibitors against glycolysis and oxidative phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the pyruvate kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development. Full article

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

► Show Figures

Figure 1

15 pages, 16104 KiB

Open AccessEditor’s ChoiceArticle

Ochratoxin A-Induced Hepatotoxicity through Phase I and Phase II Reactions Regulated by AhR in Liver Cells

by Hye Soo Shin, Hyun Jung Lee, Min Cheol Pyo, Dojin Ryu and Kwang-Won Lee

Toxins 2019, 11(7), 377; https://doi.org/10.3390/toxins11070377 - 29 Jun 2019

Cited by 47 | Viewed by 4865

Abstract

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The [...] Read more.

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress. Full article

(This article belongs to the Special Issue Ochratoxin in Food Safety and Public Health)

► Show Figures

Graphical abstract

25 pages, 15781 KiB

Open AccessEditor’s ChoiceArticle

Global Mycotoxin Occurrence in Feed: A Ten-Year Survey

by Christiane Gruber-Dorninger, Timothy Jenkins and Gerd Schatzmayr

Toxins 2019, 11(7), 375; https://doi.org/10.3390/toxins11070375 - 27 Jun 2019

Cited by 489 | Viewed by 17265

Abstract

Mycotoxins contaminating animal feed can exert toxic effects in animals and be transferred into animal products. Therefore, mycotoxin occurrence in feed should be monitored. To this end, we performed a large-scale global survey of mycotoxin contamination in feed and assessed regional differences and [...] Read more.

Mycotoxins contaminating animal feed can exert toxic effects in animals and be transferred into animal products. Therefore, mycotoxin occurrence in feed should be monitored. To this end, we performed a large-scale global survey of mycotoxin contamination in feed and assessed regional differences and year-to-year variation of mycotoxin occurrence. Concentrations of aflatoxin B₁, zearalenone, fumonisins, ochratoxin A, deoxynivalenol, and T-2 toxin were analyzed in 74,821 samples of feed and feed raw materials (e.g., maize, wheat, soybean) collected from 100 countries from 2008 to 2017. In total, 88% of the samples were contaminated with at least one mycotoxin. Mycotoxin occurrence showed distinct regional trends and climate was a key determinant governing these trends. In most regions, the majority of samples complied with maximum levels and guidance values for mycotoxins in animal feed that are in effect in the European Union. However, 41.1%, 38.5%, and 20.9% of samples from South Asia, Sub-Saharan Africa, and Southeast Asia, respectively, exceeded the maximum level for aflatoxin B₁ (20 µg/kg). In several regions, mycotoxin concentrations in maize showed a pronounced year-to-year variation that could be explained by rainfall or temperature during sensitive periods of grain development. A large fraction of samples (64%) was co-contaminated with ≥ 2 mycotoxins. Most frequently observed mycotoxin mixtures were combinations of deoxynivalenol, zearalenone, and fumonisins, as well as fumonisins and aflatoxin B₁. Deoxynivalenol and zearalenone concentrations were correlated in maize and wheat. In conclusion, according to an extensive global survey, mycotoxin (co-)contamination of animal feed is common, shows regional trends, and is governed in part by climate and weather. Full article

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

► Show Figures

Figure 1

29 pages, 747 KiB

Open AccessEditor’s ChoiceReview

Potential Therapeutic Applications of Bee Venom on Skin Disease and Its Mechanisms: A Literature Review

by Haejoong Kim, Soo-Yeon Park and Gihyun Lee

Toxins 2019, 11(7), 374; https://doi.org/10.3390/toxins11070374 - 27 Jun 2019

Cited by 43 | Viewed by 21184

Abstract

Skin is larger than any other organ in humans. Like other organs, various bacterial, viral, and inflammatory diseases, as well as cancer, affect the skin. Skin diseases like acne, atopic dermatitis, and psoriasis often reduce the quality of life seriously. Therefore, effective treatment [...] Read more.

Skin is larger than any other organ in humans. Like other organs, various bacterial, viral, and inflammatory diseases, as well as cancer, affect the skin. Skin diseases like acne, atopic dermatitis, and psoriasis often reduce the quality of life seriously. Therefore, effective treatment of skin disorders is important despite them not being life-threatening. Conventional medicines for skin diseases include corticosteroids and antimicrobial drugs, which are effective in treating many inflammatory and infectious skin diseases; however, there are growing concerns about the side effects of these therapies, especially during long-term use in relapsing or intractable diseases. Hence, many researchers are trying to develop alternative treatments, especially from natural sources, to resolve these limitations. Bee venom (BV) is an attractive candidate because many experimental and clinical reports show that BV exhibits anti-inflammatory, anti-apoptotic, anti-fibrotic, antibacterial, antiviral, antifungal, and anticancer effects. Here, we review the therapeutic applications of BV in skin diseases, including acne, alopecia, atopic dermatitis, melanoma, morphea, photoaging, psoriasis, wounds, wrinkles, and vitiligo. Moreover, we explore the therapeutic mechanisms of BV in the treatment of skin diseases and killing effects of BV on skin disease-causing pathogens, including bacteria, fungi and viruses. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

► Show Figures

Figure 1

14 pages, 604 KiB

Open AccessEditor’s ChoiceReview

Association of Pertussis Toxin with Severe Pertussis Disease

by Karen Scanlon, Ciaran Skerry and Nicholas Carbonetti

Toxins 2019, 11(7), 373; https://doi.org/10.3390/toxins11070373 - 27 Jun 2019

Cited by 43 | Viewed by 20491

Abstract

Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, [...] Read more.

Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis. Full article

(This article belongs to the Special Issue Pertussis Toxin)

► Show Figures

Figure 1

11 pages, 817 KiB

Open AccessEditor’s ChoiceReview

From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent

by Yu-Ju Kuo, Ching-Hu Chung and Tur-Fu Huang

Toxins 2019, 11(7), 372; https://doi.org/10.3390/toxins11070372 - 26 Jun 2019

Cited by 24 | Viewed by 4365

Abstract

Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell–matrix and cell–cell [...] Read more.

Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell–matrix and cell–cell interactions and for the development of antithrombotic and antiangiogenic agents according to their anti-adhesive and anti-migration effect on tumor cells and antiangiogenesis activities. Disintegrins represent a family of low molecular weight, cysteine-rich, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing polypeptides, which inhibit fibrinogen binding to integrin αIIbβ3 (i.e., platelet glycoprotein IIb/IIIa), as well as ligand binding to integrins αvβ3, and α5β1 expressed on cells (i.e., fibroblasts, tumor cells, and endothelial cells). This review focuses on the current efforts attained from studies using disintegrins as a tool in the field of arterial thrombosis, angiogenesis, inflammation, and tumor metastasis, and briefly describes their potential therapeutic applications and side effects in integrin-related diseases. Additionally, novel R(K)GD-containing disintegrin TMV-7 mutants are being designed as safer antithrombotics without causing thrombocytopenia and bleeding. Full article

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

► Show Figures

Figure 1

14 pages, 3673 KiB

Open AccessEditor’s ChoiceArticle

Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis

by Robin C. Su, Thomas M. Blomquist, Andrew L. Kleinhenz, Fatimah K. Khalaf, Prabhatchandra Dube, Apurva Lad, Joshua D. Breidenbach, Chrysan J. Mohammed, Shungang Zhang, Caitlin E. Baum, Deepak Malhotra, David J. Kennedy and Steven T. Haller

Toxins 2019, 11(6), 371; https://doi.org/10.3390/toxins11060371 - 25 Jun 2019

Cited by 29 | Viewed by 6106

Abstract

Inflammatory Bowel Disease (IBD) represents a collection of gastrointestinal disorders resulting from genetic and environmental factors. Microcystin-leucine arginine (MC-LR) is a toxin produced by cyanobacteria during algal blooms and demonstrates bioaccumulation in the intestinal tract following ingestion. Little is known about the impact [...] Read more.

Inflammatory Bowel Disease (IBD) represents a collection of gastrointestinal disorders resulting from genetic and environmental factors. Microcystin-leucine arginine (MC-LR) is a toxin produced by cyanobacteria during algal blooms and demonstrates bioaccumulation in the intestinal tract following ingestion. Little is known about the impact of MC-LR ingestion in individuals with IBD. In this study, we sought to investigate MC-LR’s effects in a dextran sulfate sodium (DSS)-induced colitis model. Mice were separated into four groups: (a) water only (control), (b) DSS followed by water (DSS), (c) water followed by MC-LR (MC-LR), and (d) DSS followed by MC-LR (DSS + MC-LR). DSS resulted in weight loss, splenomegaly, and severe colitis marked by transmural acute inflammation, ulceration, shortened colon length, and bloody stools. DSS + MC-LR mice experienced prolonged weight loss and bloody stools, increased ulceration of colonic mucosa, and shorter colon length as compared with DSS mice. DSS + MC-LR also resulted in greater increases in pro-inflammatory transcripts within colonic tissue (TNF-α, IL-1β, CD40, MCP-1) and the pro-fibrotic marker, PAI-1, as compared to DSS-only ingestion. These findings demonstrate that MC-LR exposure not only prolongs, but also worsens the severity of pre-existing colitis, strengthening evidence of MC-LR as an under-recognized environmental toxin in vulnerable populations, such as those with IBD. Full article

(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)

► Show Figures

Graphical abstract

21 pages, 2954 KiB

Open AccessEditor’s ChoicePerspective

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

by Esperanza Rivera-de-Torre, Juan Palacios-Ortega, José G. Gavilanes, Álvaro Martínez-del-Pozo and Sara García-Linares

Toxins 2019, 11(6), 370; https://doi.org/10.3390/toxins11060370 - 25 Jun 2019

Cited by 17 | Viewed by 5890

Abstract

Animal venoms are complex mixtures of highly specialized toxic molecules. Cnidarians and arachnids produce pore-forming proteins (PFPs) directed against the plasma membrane of their target cells. Among PFPs from cnidarians, actinoporins stand out for their small size and molecular simplicity. While native actinoporins [...] Read more.

Animal venoms are complex mixtures of highly specialized toxic molecules. Cnidarians and arachnids produce pore-forming proteins (PFPs) directed against the plasma membrane of their target cells. Among PFPs from cnidarians, actinoporins stand out for their small size and molecular simplicity. While native actinoporins require only sphingomyelin for membrane binding, engineered chimeras containing a recognition antibody-derived domain fused to an actinoporin isoform can nonetheless serve as highly specific immunotoxins. Examples of such constructs targeted against malignant cells have been already reported. However, PFPs from arachnid venoms are less well-studied from a structural and functional point of view. Spiders from the Latrodectus genus are professional insect hunters that, as part of their toxic arsenal, produce large PFPs known as latrotoxins. Interestingly, some latrotoxins have been identified as potent and highly-specific insecticides. Given the proteinaceous nature of these toxins, their promising future use as efficient bioinsecticides is discussed throughout this Perspective. Protein engineering and large-scale recombinant production are critical steps for the use of these PFPs as tools to control agriculturally important insect pests. In summary, both families of PFPs, from Cnidaria and Arachnida, appear to be molecules with promising biotechnological applications. Full article

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

► Show Figures

Figure 1

16 pages, 559 KiB

Open AccessEditor’s ChoiceReview

Impact of Ergot Alkaloids on Female Reproduction in Domestic Livestock Species

by Rebecca K. Poole and Daniel H. Poole

Toxins 2019, 11(6), 364; https://doi.org/10.3390/toxins11060364 - 21 Jun 2019

Cited by 21 | Viewed by 4860

Abstract

Fescue toxicosis is a multifaceted syndrome that elicits many negative effects on livestock consuming ergot alkaloids produced by endophyte-infected tall fescue. The economic losses associated with fescue toxicosis are primarily due to reproductive failure including altered cyclicity, suppressed hormone secretion, reduced pregnancy rates, [...] Read more.

Fescue toxicosis is a multifaceted syndrome that elicits many negative effects on livestock consuming ergot alkaloids produced by endophyte-infected tall fescue. The economic losses associated with fescue toxicosis are primarily due to reproductive failure including altered cyclicity, suppressed hormone secretion, reduced pregnancy rates, agalactia, and reduced offspring birth weights. For decades, a multitude of research has investigated the physiological and cellular mechanisms of these reproductive failures associated with fescue toxicosis. This review will summarize the various effects of ergot alkaloids on female reproduction in grazing livestock species. Full article

(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)

► Show Figures

Figure 1

7 pages, 708 KiB

Open AccessEditor’s ChoiceCommunication

Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium

by Hiroshi Nagai, Shingo Sato, Kaori Iida, Kazutaka Hayashi, Mioko Kawaguchi, Hajime Uchida and Masayuki Satake

Toxins 2019, 11(6), 366; https://doi.org/10.3390/toxins11060366 - 21 Jun 2019

Cited by 29 | Viewed by 4094

Abstract

Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is aplysiatoxin. We have isolated various [...] Read more.

Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is aplysiatoxin. We have isolated various aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid–liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis. Full article

(This article belongs to the Special Issue Marine Toxins Detection)

► Show Figures

Figure 1

21 pages, 2502 KiB

Open AccessEditor’s ChoiceArticle

Chemical Synthesis, Proper Folding, Na_v Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1

by Sébastien Nicolas, Claude Zoukimian, Frank Bosmans, Jérôme Montnach, Sylvie Diochot, Eva Cuypers, Stephan De Waard, Rémy Béroud, Dietrich Mebs, David Craik, Didier Boturyn, Michel Lazdunski, Jan Tytgat and Michel De Waard

Toxins 2019, 11(6), 367; https://doi.org/10.3390/toxins11060367 - 21 Jun 2019

Cited by 20 | Viewed by 5157

Abstract

Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (Phlogius species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide [...] Read more.

Phlotoxin-1 (PhlTx1) is a peptide previously identified in tarantula venom (Phlogius species) that belongs to the inhibitory cysteine-knot (ICK) toxin family. Like many ICK-based spider toxins, the synthesis of PhlTx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. Herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of PhlTx1 that allows for a straightforward production of this challenging peptide. We also performed extensive functional testing of PhlTx1 on 31 ion channel types and identified the voltage-gated sodium (Na_v) channel Na_v1.7 as the main target of this toxin. Moreover, we compared PhlTx1 activity to 10 other spider toxin activities on an automated patch-clamp system with Chinese Hamster Ovary (CHO) cells expressing human Na_v1.7. Performing these analyses in reproducible conditions allowed for classification according to the potency of the best natural Na_v1.7 peptide blockers. Finally, subsequent in vivo testing revealed that intrathecal injection of PhlTx1 reduces the response of mice to formalin in both the acute pain and inflammation phase without signs of neurotoxicity. PhlTx1 is thus an interesting toxin to investigate Na_v1.7 involvement in cellular excitability and pain. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

► Show Figures

Figure 1

10 pages, 662 KiB

Open AccessEditor’s ChoiceArticle

Structural Domains of the Bacillus thuringiensis Vip3Af Protein Unraveled by Tryptic Digestion of Alanine Mutants

by Yudong Quan and Juan Ferré

Toxins 2019, 11(6), 368; https://doi.org/10.3390/toxins11060368 - 21 Jun 2019

Cited by 20 | Viewed by 3510

Abstract

Vip3 proteins are increasingly used in insect control in transgenic crops. To shed light on the structure of these proteins, we used the approach of the trypsin fragmentation of mutants altering the conformation of the Vip3Af protein. From an alanine scanning of Vip3Af, [...] Read more.

Vip3 proteins are increasingly used in insect control in transgenic crops. To shed light on the structure of these proteins, we used the approach of the trypsin fragmentation of mutants altering the conformation of the Vip3Af protein. From an alanine scanning of Vip3Af, we selected mutants with an altered proteolytic pattern. Based on protease digestion patterns, their effect on oligomer formation, and theoretical cleavage sites, we generated a map of the Vip3Af protein with five domains which match some of the domains proposed independently by two in silico models. Domain I ranges amino acids (aa) 12–198, domain II aa199–313, domain III aa314–526, domain IV aa527–668, and domain V aa669–788. The effect of some mutations on the ability to form a tetrameric molecule revealed that domains I–II are required for tetramerization, while domain V is not. The involvement of domain IV in the tetramer formation is not clear. Some mutations distributed from near the end of domain I up to the end of domain II affect the stability of the first three domains of the protein and destroy the tetrameric form upon trypsin treatment. Because of the high sequence similarity among Vip3 proteins, we propose that our domain map can be extended to the Vip3 family of proteins. Full article

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

► Show Figures

Figure 1

13 pages, 2003 KiB

Open AccessEditor’s ChoiceArticle

Phytochemicals of Apple Pomace as Prospect Bio-Fungicide Agents against Mycotoxigenic Fungal Species—In Vitro Experiments

by Marta Oleszek, Łukasz Pecio, Solomiia Kozachok, Żaneta Lachowska-Filipiuk, Karolina Oszust and Magdalena Frąc

Toxins 2019, 11(6), 361; https://doi.org/10.3390/toxins11060361 - 20 Jun 2019

Cited by 31 | Viewed by 4084

Abstract

The phytochemical constituents of apple waste were established as potential antifungal agents against four crops pathogens, specifically, Botrytis sp., Fusarium oxysporum, Petriella setifera, and Neosartorya fischeri. Crude, purified extracts and fractions of apple pomace were tested in vitro to evaluate their [...] Read more.

The phytochemical constituents of apple waste were established as potential antifungal agents against four crops pathogens, specifically, Botrytis sp., Fusarium oxysporum, Petriella setifera, and Neosartorya fischeri. Crude, purified extracts and fractions of apple pomace were tested in vitro to evaluate their antifungal and antioxidant properties. The phytochemical constituents of the tested materials were mainly represented by phloridzin and quercetin derivatives, as well as previously undescribed in apples, monoterpene–pinnatifidanoside D. Its structure was confirmed by 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopic analyses. The fraction containing quercetin pentosides possessed the highest antioxidant activity, while the strongest antifungal activity was exerted by a fraction containing phloridzin. Sugar moieties differentiated the antifungal activity of quercetin glycosides. Quercetin hexosides possessed stronger antifungal activity than quercetin pentosides. Full article

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

► Show Figures

Figure 1

29 pages, 3450 KiB

Open AccessEditor’s ChoiceReview

The Urgent Need to Develop Novel Strategies for the Diagnosis and Treatment of Snakebites

by Harry F. Williams, Harry J. Layfield, Thomas Vallance, Ketan Patel, Andrew B. Bicknell, Steven A. Trim and Sakthivel Vaiyapuri

Toxins 2019, 11(6), 363; https://doi.org/10.3390/toxins11060363 - 20 Jun 2019

Cited by 87 | Viewed by 19826

Abstract

Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated [...] Read more.

Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA₂ inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late to effectively treat SBE. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, with new treatments and diagnostics rapidly emerging. Here we critically review the urgent necessity for the development of diagnostic tools and improved therapeutics to mitigate the deaths and disabilities caused by SBE. Full article

(This article belongs to the Special Issue Novel Strategies for the Diagnosis and Treatment of Snakebites)

► Show Figures

Figure 1

18 pages, 1461 KiB

Open AccessEditor’s ChoiceReview

An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation

by Roger Astley, Frederick C. Miller, Md Huzzatul Mursalin, Phillip S. Coburn and Michelle C. Callegan

Toxins 2019, 11(6), 356; https://doi.org/10.3390/toxins11060356 - 19 Jun 2019

Cited by 49 | Viewed by 14865

Abstract

Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes [...] Read more.

Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes capable of causing profound damage to tissues and organs, as well as modulating the immune response to these infections. Unfortunately, in the context of ocular infections, this can mean blindness for the patient. The role of α-toxin in corneal infection (keratitis) and infection of the interior of the eye (endophthalmitis) has been well established by comparing virulence in animal models and α-toxin-deficient isogenic mutants with their wild-type parental strains. The importance of other toxins, such as β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL), have been analyzed to a lesser degree and their roles in eye infections are less clear. Other toxins such as the phenol-soluble modulins have yet to be examined in any animal models for their contributions to virulence in eye infections. This review discusses the state of current knowledge of the roles of S. aureus toxins in eye infections and the controversies existing as a result of the use of different infection models. The strengths and limitations of these ocular infection models are discussed, as well as the need for physiological relevance in the study of staphylococcal toxins in these models. Full article

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

► Show Figures

Figure 1

14 pages, 1399 KiB

Open AccessEditor’s ChoiceArticle

Emerging Fusarium Mycotoxins Fusaproliferin, Beauvericin, Enniatins, and Moniliformin in Serbian Maize

by Igor Jajić, Tatjana Dudaš, Saša Krstović, Rudolf Krska, Michael Sulyok, Ferenc Bagi, Zagorka Savić, Darko Guljaš and Aleksandra Stankov

Toxins 2019, 11(6), 357; https://doi.org/10.3390/toxins11060357 - 19 Jun 2019

Cited by 58 | Viewed by 6213

Abstract

Emerging mycotoxins such as moniliformin (MON), enniatins (ENs), beauvericin (BEA), and fusaproliferin (FUS) may contaminate maize and negatively influence the yield and quality of grain. The aim of this study was to determine the content of emerging Fusarium mycotoxins in Serbian maize from [...] Read more.

Emerging mycotoxins such as moniliformin (MON), enniatins (ENs), beauvericin (BEA), and fusaproliferin (FUS) may contaminate maize and negatively influence the yield and quality of grain. The aim of this study was to determine the content of emerging Fusarium mycotoxins in Serbian maize from the 2016, 2017, and 2018 harvests. A total of 190 samples from commercial maize production operations in Serbia were analyzed for the presence of MON, ENs, BEA, and FUS using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The obtained results were interpreted together with weather data from each year. MON, BEA, and FUS were major contaminants, while other emerging mycotoxins were not detected or were found in fewer samples (<20%). Overall contamination was highest in 2016 when MON and BEA were found in 50–80% of samples. In 2017 and 2018, high levels of MON, FUS, and BEA were detected in regions with high precipitation and warm weather during the silking phase of maize (July and the beginning of August), when the plants are most susceptible to Fusarium infections. Since environmental conditions in Serbia are favorable for the occurrence of mycotoxigenic fungi, monitoring Fusarium toxins is essential for the production of safe food and feed. Full article

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

► Show Figures

Figure 1

22 pages, 2162 KiB

Open AccessEditor’s ChoiceReview

Brown Spider (Loxosceles) Venom Toxins as Potential Biotools for the Development of Novel Therapeutics

by Daniele Chaves-Moreira, Fernando Hitomi Matsubara, Zelinda Schemczssen-Graeff, Elidiana De Bona, Vanessa Ribeiro Heidemann, Clara Guerra-Duarte, Luiza Helena Gremski, Carlos Chávez-Olórtegui, Andrea Senff-Ribeiro, Olga Meiri Chaim, Raghuvir Krishnaswamy Arni and Silvio Sanches Veiga

Toxins 2019, 11(6), 355; https://doi.org/10.3390/toxins11060355 - 19 Jun 2019

Cited by 24 | Viewed by 6137

Abstract

Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic manifestations such as renal failure and hematological disturbances. Several toxins make up the venom of these species, and they are mainly peptides [...] Read more.

Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic manifestations such as renal failure and hematological disturbances. Several toxins make up the venom of these species, and they are mainly peptides and proteins ranging from 5–40 kDa. The venoms have three major families of toxins: phospholipases-D, astacin-like metalloproteases, and the inhibitor cystine knot (ICK) peptides. Serine proteases, serpins, hyaluronidases, venom allergens, and a translationally controlled tumor protein (TCTP) are also present. Toxins hold essential biological properties that enable interactions with a range of distinct molecular targets. Therefore, the application of toxins as research tools and clinical products motivates repurposing their uses of interest. This review aims to discuss possibilities for brown spider venom toxins as putative models for designing molecules likely for therapeutics based on the status quo of brown spider venoms. Herein, we explore new possibilities for the venom components in the context of their biochemical and biological features, likewise their cellular targets, three-dimensional structures, and mechanisms of action. Full article

(This article belongs to the Special Issue Arthropod Venom Components and Their Potential Usage)

► Show Figures

Figure 1

18 pages, 1836 KiB

Open AccessEditor’s ChoiceReview

Membrane Permeabilization by Pore-Forming RTX Toxins: What Kind of Lesions Do These Toxins Form?

by Helena Ostolaza, David González-Bullón, Kepa B. Uribe, Cesar Martín, Jone Amuategi and Xabier Fernandez-Martínez

Toxins 2019, 11(6), 354; https://doi.org/10.3390/toxins11060354 - 18 Jun 2019

Cited by 32 | Viewed by 9219

Abstract

Pore-forming toxins (PFTs) form nanoscale pores across target membranes causing cell death. The pore-forming cytolysins of the RTX (repeats in toxin) family belong to a steadily increasing family of proteins characterized by having in their primary sequences a number of glycine- and aspartate-rich [...] Read more.

Pore-forming toxins (PFTs) form nanoscale pores across target membranes causing cell death. The pore-forming cytolysins of the RTX (repeats in toxin) family belong to a steadily increasing family of proteins characterized by having in their primary sequences a number of glycine- and aspartate-rich nonapeptide repeats. They are secreted by a variety of Gram-negative bacteria and form ion-permeable pores in several cell types, such as immune cells, epithelial cells, or erythrocytes. Pore-formation by RTX-toxins leads to the dissipation of ionic gradients and membrane potential across the cytoplasmic membrane of target cells, which results in cell death. The pores formed in lipid bilayers by the RTX-toxins share some common properties such as cation selectivity and voltage-dependence. Hemolytic and cytolytic RTX-toxins are important virulence factors in the pathogenesis of the producing bacteria. And hence, understanding the function of these proteins at the molecular level is critical to elucidating their role in disease processes. In this review we summarize the current state of knowledge on pore-formation by RTX toxins, and include recent results from our own laboratory regarding the pore-forming activity of adenylate cyclase toxin (ACT or CyaA), a large protein toxin secreted by Bordetella pertussis, the bacterium causative of whooping cough. Full article

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

► Show Figures

Figure 1

37 pages, 2584 KiB

Open AccessEditor’s ChoiceReview

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin

by Natalia Sowa-Rogozińska, Hanna Sominka, Jowita Nowakowska-Gołacka, Kirsten Sandvig and Monika Słomińska-Wojewódzka

Toxins 2019, 11(6), 350; https://doi.org/10.3390/toxins11060350 - 18 Jun 2019

Cited by 61 | Viewed by 12350

Abstract

Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical [...] Read more.

Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin. Full article

(This article belongs to the Special Issue Ricin Toxins)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI