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Toxins, Volume 9, Issue 12 (December 2017)

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Cover Story (view full-size image) Computer-aided design of the bioreceptor for ochratoxin monitoring: In solution, the unmodified [...] Read more.
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Open AccessReview Microbial Inhibition of Fusarium Pathogens and Biological Modification of Trichothecenes in Cereal Grains
Toxins 2017, 9(12), 408; https://doi.org/10.3390/toxins9120408
Received: 1 November 2017 / Revised: 15 December 2017 / Accepted: 18 December 2017 / Published: 20 December 2017
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Abstract
Fungi of the genus Fusarium infect cereal crops during the growing season and cause head blight and other diseases. Their toxic secondary metabolites (mycotoxins) contaminate grains. Several dozen toxic compounds produced by fungal pathogens have been identified to date. Type B trichothecenes—deoxynivalenol, its
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Fungi of the genus Fusarium infect cereal crops during the growing season and cause head blight and other diseases. Their toxic secondary metabolites (mycotoxins) contaminate grains. Several dozen toxic compounds produced by fungal pathogens have been identified to date. Type B trichothecenes—deoxynivalenol, its acetyl derivatives and nivalenol (produced mainly by F. graminearum and F. culmorum)—are most commonly detected in cereal grains. “T-2 toxin” (produced by, among others, F. sporotrichioides) belongs to type-A trichothecenes which are more toxic than other trichothecenes. Antagonistic bacteria and fungi can affect pathogens of the genus Fusarium via different modes of action: direct (mycoparasitism or hyperparasitism), mixed-path (antibiotic secretion, production of lytic enzymes) and indirect (induction of host defense responses). Microbial modification of trichothecenes involves acetylation, deacetylation, oxidation, de-epoxidation, and epimerization, and it lowers the pathogenic potential of fungi of the genus Fusarium. Other modifing mechanisms described in the paper involve the physical adsorption of mycotoxins in bacterial cells and the conjugation of mycotoxins to glucose and other compounds in plant and fungal cells. The development of several patents supports the commercialization and wider application of microorganisms biodegrading mycotoxins in grains and, consequently, in feed additives. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Food-Borne Outbreak Investigation and Molecular Typing: High Diversity of Staphylococcus aureus Strains and Importance of Toxin Detection
Toxins 2017, 9(12), 407; https://doi.org/10.3390/toxins9120407
Received: 14 November 2017 / Revised: 15 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
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Abstract
Staphylococcus aureus is an important aetiological agent of food intoxications in the European Union as it can cause gastro-enteritis through the production of various staphylococcal enterotoxins (SEs) in foods. Reported enterotoxin dose levels causing food-borne illness are scarce and varying. Three food poisoning
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Staphylococcus aureus is an important aetiological agent of food intoxications in the European Union as it can cause gastro-enteritis through the production of various staphylococcal enterotoxins (SEs) in foods. Reported enterotoxin dose levels causing food-borne illness are scarce and varying. Three food poisoning outbreaks due to enterotoxin-producing S. aureus strains which occurred in 2013 in Belgium are described. The outbreaks occurred in an elderly home, at a barbecue event and in a kindergarten and involved 28, 18, and six cases, respectively. Various food leftovers contained coagulase positive staphylococci (CPS). Low levels of staphylococcal enterotoxins ranging between 0.015 ng/g and 0.019 ng/g for enterotoxin A (SEA), and corresponding to 0.132 ng/g for SEC were quantified in the food leftovers for two of the reported outbreaks. Molecular typing of human and food isolates using pulsed-field gel electrophoresis (PFGE) and enterotoxin gene typing, confirmed the link between patients and the suspected foodstuffs. This also demonstrated the high diversity of CPS isolates both in the cases and in healthy persons carrying enterotoxin genes encoding emetic SEs for which no detection methods currently exist. For one outbreak, the investigation pointed out to the food handler who transmitted the outbreak strain to the food. Tools to improve staphylococcal food poisoning (SFP) investigations are presented. Full article
(This article belongs to the collection Staphylococcus aureus Toxins)
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Open AccessReview Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia
Toxins 2017, 9(12), 406; https://doi.org/10.3390/toxins9120406
Received: 30 October 2017 / Revised: 13 December 2017 / Accepted: 16 December 2017 / Published: 19 December 2017
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Abstract
Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted
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Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A2 (sPLA2s). These PLA2 belong to distinct PLA2s groups. For example, snake venom sPLA2s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA2 belongs to group III of sPLA2s. It is well known that PLA2, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA2s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA2s from animal venoms, particularly snake venoms. Full article
(This article belongs to the Special Issue Animal Venoms and Pain)
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Open AccessArticle Effects of Continuously Feeding Diets Containing Cereal Ergot Alkaloids on Nutrient Digestibility, Alkaloid Recovery in Feces, and Performance Traits of Ram Lambs
Toxins 2017, 9(12), 405; https://doi.org/10.3390/toxins9120405
Received: 26 October 2017 / Revised: 5 December 2017 / Accepted: 14 December 2017 / Published: 19 December 2017
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Abstract
Allowable limits for cereal ergot alkaloids in livestock feeds are being re-examined, and the objective of this study was to compare nutrient digestibility, growth performance and carcass characteristics of ram lambs fed a range of alkaloid concentrations, including the maximum currently allowed in
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Allowable limits for cereal ergot alkaloids in livestock feeds are being re-examined, and the objective of this study was to compare nutrient digestibility, growth performance and carcass characteristics of ram lambs fed a range of alkaloid concentrations, including the maximum currently allowed in Canada (2 to 3 ppm). Four pelleted diets were fed: control, with no added alkaloids; 930; 1402; and 2447 ppb alkaloids based on total R and S epimers. Eight ram lambs (30.0 ± 3.1 kg) were used to examine the impacts of dietary treatments on nutrient digestibility and alkaloid recovery from feces. Concentrations of dietary alkaloids evaluated did not affect nutrient digestibility or N metabolism. Excepting ergocornine and ergocryptine, recovery of alkaloids in feces varied among periods, suggesting that individual lambs may differ in their ability to metabolize ergocristine, ergometrine, ergosine, ergotamine and their S epimers. In a second experiment, ram lambs (n = 47, 30 ± 8 kg) were randomly assigned to a diet and weighed weekly until they achieved a slaughter weight of ≥ 45 kg (average 9 weeks; range 6 to 13 weeks). Intake of DM did not differ (p = 0.91) among diets, although lambs fed 2447 ppb alkaloids had a lower (p < 0.01) ADG than did lambs receiving other treatments. The concentration of serum prolactin linearly declined (p < 0.01) with increasing alkaloids. Feeding 2447 ppb total alkaloids negatively impacted growth, while feeding 1402 ppb did not harm growth performance, but reduced carcass dressing percentage. Due to different concentrations of alkaloids affecting growth and carcass characteristics in the present study, determining allowable limits for total dietary alkaloids will require a better understanding of impacts of alkaloid profiles and interactions among individual alkaloids. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessEditor’s ChoiceCommunication High Conservation of Tetanus and Botulinum Neurotoxins Cleavage Sites on Human SNARE Proteins Suggests That These Pathogens Exerted Little or No Evolutionary Pressure on Humans
Toxins 2017, 9(12), 404; https://doi.org/10.3390/toxins9120404
Received: 7 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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Abstract
The Genome Aggregation Database presently contains >120,000 human genomes. We searched in this database for the presence of mutations at the sites of tetanus (TeNT) and botulinum neurotoxins (BoNTs) cleavages of the three SNARE proteins: VAMP, SNAP-25 and Syntaxin. These mutations could account
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The Genome Aggregation Database presently contains >120,000 human genomes. We searched in this database for the presence of mutations at the sites of tetanus (TeNT) and botulinum neurotoxins (BoNTs) cleavages of the three SNARE proteins: VAMP, SNAP-25 and Syntaxin. These mutations could account for some of the BoNT/A resistant patients. At the same time, this approach was aimed at testing the possibility that TeNT and BoNT may have acted as selective agents in the development of resistance to tetanus or botulism. We found that mutations of the SNARE proteins are very rare and concentrated outside the SNARE motif required for the formation of the SNARE complex involved in neuroexocytosis. No changes were found at the BoNT cleavage sites of VAMP and syntaxins and only one very rare mutation was found in the essential C-terminus region of SNAP-25, where Arg198 was replaced with a Cys residue. This is the P1’ cleavage site for BoNT/A and the P1 cleavage site for BoNT/C. We found that the Arg198Cys mutation renders SNAP-25 resistant to BoNT/A. Nonetheless, its low frequency (1.8 × 10−5) indicates that mutations of SNAP-25 at the BoNT/A cleavage site are unlikely to account for the existence of BoNT/A resistant patients. More in general, the present findings indicate that tetanus and botulinum neurotoxins have not acted as selective agents during human evolution as it appears to have been the case for tetanus in rats and chicken. Full article
(This article belongs to the Section Bacterial Toxins)
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Open AccessReview Botulinum Toxin in the Field of Dermatology: Novel Indications
Toxins 2017, 9(12), 403; https://doi.org/10.3390/toxins9120403
Received: 20 November 2017 / Revised: 13 December 2017 / Accepted: 14 December 2017 / Published: 16 December 2017
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Abstract
Since its approval by the US Food and Drug Administration in 2002 for glabellar wrinkles, botulinum toxin (BTX) has been widely used to correct facial wrinkles. As a result, many consider BTX synonymous with cosmetic dermatology. Recent studies indicate that BTX elicits biological
[...] Read more.
Since its approval by the US Food and Drug Administration in 2002 for glabellar wrinkles, botulinum toxin (BTX) has been widely used to correct facial wrinkles. As a result, many consider BTX synonymous with cosmetic dermatology. Recent studies indicate that BTX elicits biological effects on various skin cell types via the modulation of neurotransmitter release, and it seems that BTX has a wider zone of dermatologic influence than originally understood. Clinicians and researchers are now beginning to explore the potential of BTX beyond the amelioration of facial lines and encouraging results are seen with BTX in a variety of skin conditions. In this paper, we review novel dermatological indications of BTX which includes (but not limited to) scar prevention, facial flushing, post-herpetic neuralgia and itch. These areas show great promise, but there is definite need for larger, double-blinded, randomized control trials against established treatments before BTX becomes a clinical reality. Full article
Open AccessReview In Vitro Toxicological Assessment of Cylindrospermopsin: A Review
Toxins 2017, 9(12), 402; https://doi.org/10.3390/toxins9120402
Received: 6 November 2017 / Revised: 12 December 2017 / Accepted: 13 December 2017 / Published: 16 December 2017
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Abstract
Cylindrospermopsin (CYN) is a cyanobacterial toxin that is gaining importance, owing to its increasing expansion worldwide and the increased frequency of its blooms. CYN mainly targets the liver, but also involves other organs. Various mechanisms have been associated with its toxicity, such as
[...] Read more.
Cylindrospermopsin (CYN) is a cyanobacterial toxin that is gaining importance, owing to its increasing expansion worldwide and the increased frequency of its blooms. CYN mainly targets the liver, but also involves other organs. Various mechanisms have been associated with its toxicity, such as protein synthesis inhibition, oxidative stress, etc. However, its toxic effects are not yet fully elucidated and additional data for hazard characterization purposes are required. In this regard, in vitro methods can play an important role, owing to their advantages in comparison to in vivo trials. The aim of this work was to compile and evaluate the in vitro data dealing with CYN available in the scientific literature, focusing on its toxicokinetics and its main toxicity mechanisms. This analysis would be useful to identify research needs and data gaps in order to complete knowledge about the toxicity profile of CYN. For example, it has been shown that research on various aspects, such as new emerging toxicity effects, the toxicity of analogs, or the potential interaction of CYN with other cyanotoxins, among others, is still very scarce. New in vitro studies are therefore welcome. Full article
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
Open AccessReview Expression of Staphylococcal Enterotoxins under Stress Encountered during Food Production and Preservation
Toxins 2017, 9(12), 401; https://doi.org/10.3390/toxins9120401
Received: 19 November 2017 / Revised: 12 December 2017 / Accepted: 14 December 2017 / Published: 15 December 2017
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Abstract
Staphylococcal food poisoning (SFP) is the most prevalent cause of food-borne intoxications worldwide. Consumption of enterotoxins preformed in food causes violent vomiting and can be fatal in children and the elderly. While being repressed by competing bacteria in most matrices, Staphylococcus aureus benefits
[...] Read more.
Staphylococcal food poisoning (SFP) is the most prevalent cause of food-borne intoxications worldwide. Consumption of enterotoxins preformed in food causes violent vomiting and can be fatal in children and the elderly. While being repressed by competing bacteria in most matrices, Staphylococcus aureus benefits from crucial competitive advantages in foods with high osmolarity or low pH. During recent years, the long-standing belief in the feasibility of assessing SFP risk based on colony-forming units of S. aureus present in food products has been disproven. Instead, researchers and food business operators are acutely aware of the imminent threat arising from unforeseeable enterotoxin production under stress conditions. This paradigm shift led to a variety of new publications enabling an improved understanding of enterotoxin expression under stress conditions encountered in food. The wealth of data provided by these studies is extremely diverse, as it is based on different methodological approaches, staphylococcal strains, stressors, and enterotoxins. Therefore, in this review, we aggregated and critically evaluated the complex findings of these studies, to provide readers with a current overview of the state of research in the field. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
Open AccessArticle Investigating β-N-Methylamino-l-alanine Misincorporation in Human Cell Cultures: A Comparative Study with Known Amino Acid Analogues
Toxins 2017, 9(12), 400; https://doi.org/10.3390/toxins9120400
Received: 30 November 2017 / Revised: 12 December 2017 / Accepted: 13 December 2017 / Published: 14 December 2017
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Abstract
Misincorporation of β-N-methylamino-l-alanine (BMAA) into proteins has been proposed to be a mechanism of toxicity to explain the role of BMAA in neurodegenerative disease development. However, studies have shown that all detectable BMAA can be removed from proteins by
[...] Read more.
Misincorporation of β-N-methylamino-l-alanine (BMAA) into proteins has been proposed to be a mechanism of toxicity to explain the role of BMAA in neurodegenerative disease development. However, studies have shown that all detectable BMAA can be removed from proteins by SDS-PAGE purification and that the toxicity of l-canavanine cannot be reproduced in prokaryotes or in a rat pheochromocytoma cell line, strongly indicating that the misincorporation hypothesis of BMAA should be re-investigated. The aim of this study was therefore to determine if BMAA misincorporates into proteins in cells of human origin with subsequent misincorporation-type toxicity. Almost complete loss of viability in response to exposure to l-4-fluorophenylalanine and l-m-tyrosine was observed in all of the cell lines, corresponding to a concentration-dependent increase of the analogues in protein extracts from exposed cells. In contrast, BMAA exposure resulted in slight toxicity in one of the cell lines but the observed toxicity was not the result of misincorporation of BMAA into proteins, as no BMAA was detected in any of the SDS-PAGE purified protein extracts that were obtained from the cells following BMAA exposure. The results show that BMAA is not misincorporated into human proteins and that misincorporation is not a valid mechanism of toxicity. Full article
(This article belongs to the Special Issue The Cyanobacterial Neurotoxin BMAA)
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Open AccessArticle A Deeper Examination of Thorellius atrox Scorpion Venom Components with Omic Technologies
Toxins 2017, 9(12), 399; https://doi.org/10.3390/toxins9120399
Received: 27 October 2017 / Revised: 7 December 2017 / Accepted: 8 December 2017 / Published: 12 December 2017
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Abstract
This communication reports a further examination of venom gland transcripts and venom composition of the Mexican scorpion Thorellius atrox using RNA-seq and tandem mass spectrometry. The RNA-seq, which was performed with the Illumina protocol, yielded more than 20,000 assembled transcripts. Following a database
[...] Read more.
This communication reports a further examination of venom gland transcripts and venom composition of the Mexican scorpion Thorellius atrox using RNA-seq and tandem mass spectrometry. The RNA-seq, which was performed with the Illumina protocol, yielded more than 20,000 assembled transcripts. Following a database search and annotation strategy, 160 transcripts were identified, potentially coding for venom components. A novel sequence was identified that potentially codes for a peptide with similarity to spider ω-agatoxins, which act on voltage-gated calcium channels, not known before to exist in scorpion venoms. Analogous transcripts were found in other scorpion species. They could represent members of a new scorpion toxin family, here named omegascorpins. The mass fingerprint by LC-MS identified 135 individual venom components, five of which matched with the theoretical masses of putative peptides translated from the transcriptome. The LC-MS/MS de novo sequencing allowed to reconstruct and identify 42 proteins encoded by assembled transcripts, thus validating the transcriptome analysis. Earlier studies conducted with this scorpion venom permitted the identification of only twenty putative venom components. The present work performed with more powerful and modern omic technologies demonstrates the capacity of accomplishing a deeper characterization of scorpion venom components and the identification of novel molecules with potential applications in biomedicine and the study of ion channel physiology. Full article
(This article belongs to the Special Issue Scorpion Toxins)
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Open AccessReview Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules
Toxins 2017, 9(12), 398; https://doi.org/10.3390/toxins9120398
Received: 2 November 2017 / Revised: 7 December 2017 / Accepted: 8 December 2017 / Published: 10 December 2017
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Abstract
Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion
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Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation. Full article
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Open AccessEditorial Editorial for Special Issue: The Insecticidal Bacterial Toxins in Modern Agriculture
Toxins 2017, 9(12), 396; https://doi.org/10.3390/toxins9120396
Received: 29 November 2017 / Revised: 4 December 2017 / Accepted: 4 December 2017 / Published: 9 December 2017
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Open AccessReview Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery
Toxins 2017, 9(12), 397; https://doi.org/10.3390/toxins9120397
Received: 26 October 2017 / Revised: 28 November 2017 / Accepted: 4 December 2017 / Published: 7 December 2017
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Abstract
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named
[...] Read more.
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With the rapid development of genomics and bioinformatics in recent years, functional predictions and investigations on conotoxins are making great progress in promoting the discovery of novel drugs. For example, ω-MVIIA was approved by the U.S. Food and Drug Administration in 2004 to treat chronic pain, and nine more conotoxins are at various stages of preclinical or clinical evaluation. In short, the genus Conus, the big family of cone snails, has become an important genetic resource for conotoxin identification and drug development. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology) Printed Edition available
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Open AccessPerspective Molecular Modeling and Simulation Tools in the Development of Peptide-Based Biosensors for Mycotoxin Detection: Example of Ochratoxin
Toxins 2017, 9(12), 395; https://doi.org/10.3390/toxins9120395
Received: 7 November 2017 / Revised: 28 November 2017 / Accepted: 3 December 2017 / Published: 6 December 2017
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Abstract
Mycotoxin contamination of food and feed is now ubiquitous. Exposures to mycotoxin via contact or ingestion can potentially induce adverse health outcomes. Affordable mycotoxin-monitoring systems are highly desired but are limited by (a) the reliance on technically challenging and costly molecular recognition by
[...] Read more.
Mycotoxin contamination of food and feed is now ubiquitous. Exposures to mycotoxin via contact or ingestion can potentially induce adverse health outcomes. Affordable mycotoxin-monitoring systems are highly desired but are limited by (a) the reliance on technically challenging and costly molecular recognition by immuno-capture technologies; and (b) the lack of predictive tools for directing the optimization of alternative molecular recognition modalities. Our group has been exploring the development of ochratoxin detection and monitoring systems using the peptide NFO4 as the molecular recognition receptor in fluorescence, electrochemical and multimodal biosensors. Using ochratoxin as the model mycotoxin, we share our perspective on addressing the technical challenges involved in biosensor fabrication, namely: (a) peptide receptor design; and (b) performance evaluation. Subsequently, the scope and utility of molecular modeling and simulation (MMS) approaches to address the above challenges are described. Informed and enabled by phage display, the subsequent application of MMS approaches can rationally guide subsequent biomolecular engineering of peptide receptors, including bioconjugation and bioimmobilization approaches to be used in the fabrication of peptide biosensors. MMS approaches thus have the potential to reduce biosensor development cost, extend product life cycle, and facilitate multi-analyte detection of mycotoxins, each of which positively contributes to the overall affordability of mycotoxin biosensor monitoring systems. Full article
(This article belongs to the Special Issue Advanced Sensors for Toxins)
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Open AccessReview The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
Toxins 2017, 9(12), 394; https://doi.org/10.3390/toxins9120394
Received: 1 November 2017 / Revised: 24 November 2017 / Accepted: 29 November 2017 / Published: 6 December 2017
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Abstract
Shock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET
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Shock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET respectively) both cause shock and likely contribute to the high lethality rate with B. anthracis. Selective inhibition of the toxins is protective in infection models, and administration of either toxin alone in animals produces hypotension with accompanying organ injury and lethality. Shock during infection is typically due to one of two mechanisms: (i) intravascular volume depletion related to disruption of endothelial barrier function; and (ii) extravasation of fluid and/or maladaptive dilation of peripheral resistance arteries. Although some data suggests that LT can produce myocardial dysfunction, growing evidence demonstrates that it may also interfere with endothelial integrity thereby contributing to the extravasation of fluid that helps characterize severe B. anthracis infection. Edema toxin, on the other hand, while known to produce localized tissue edema when injected subcutaneously, has potent vascular relaxant effects that could lead to pathologic arterial dilation. This review will examine recent data supporting a role for these two pathophysiologic mechanisms underlying the shock LT and ET produce. Further research and a better understanding of these mechanisms may lead to improved management of B. anthracis in patients. Full article
(This article belongs to the Section Bacterial Toxins)
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