Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Toxins, Volume 9, Issue 9 (September 2017)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-38
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle Genetic Divergence and Chemotype Diversity in the Fusarium Head Blight Pathogen Fusarium poae
Toxins 2017, 9(9), 255; doi:10.3390/toxins9090255
Received: 30 June 2017 / Accepted: 19 August 2017 / Published: 23 August 2017
PDF Full-text (1826 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fusarium head blight is a disease caused by a complex of Fusarium species. F. poae is omnipresent throughout Europe in spite of its low virulence. In this study, we assessed a geographically diverse collection of F. poae isolates for its genetic diversity using
[...] Read more.
Fusarium head blight is a disease caused by a complex of Fusarium species. F. poae is omnipresent throughout Europe in spite of its low virulence. In this study, we assessed a geographically diverse collection of F. poae isolates for its genetic diversity using AFLP (Amplified Fragment Length Polymorphism). Furthermore, studying the mating type locus and chromosomal insertions, we identified hallmarks of both sexual recombination and clonal spread of successful genotypes in the population. Despite the large genetic variation found, all F. poae isolates possess the nivalenol chemotype based on Tri7 sequence analysis. Nevertheless, Tri gene clusters showed two layers of genetic variability. Firstly, the Tri1 locus was highly variable with mostly synonymous mutations and mutations in introns pointing to a strong purifying selection pressure. Secondly, in a subset of isolates, the main trichothecene gene cluster was invaded by a transposable element between Tri5 and Tri6. To investigate the impact of these variations on the phenotypic chemotype, mycotoxin production was assessed on artificial medium. Complex blends of type A and type B trichothecenes were produced but neither genetic variability in the Tri genes nor variability in the genome or geography accounted for the divergence in trichothecene production. In view of its complex chemotype, it will be of utmost interest to uncover the role of trichothecenes in virulence, spread and survival of F. poae. Full article
(This article belongs to the Section Mycotoxins)
Figures

Figure 1

Open AccessArticle Spectral EMG Changes in Cervical Dystonia Patients and the Influence of Botulinum Toxin Treatment
Toxins 2017, 9(9), 256; doi:10.3390/toxins9090256
Received: 4 July 2017 / Revised: 10 August 2017 / Accepted: 14 August 2017 / Published: 23 August 2017
PDF Full-text (3161 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Botulinum toxin (BoNT) injections in the dystonic muscles is the preferred treatment for Cervical Dystonia (CD), but the proper identification of the dystonic muscles remains a challenge. Previous studies showed decreased 8–14 Hz autospectral power in the electromyography (EMG) of splenius muscles in
[...] Read more.
Botulinum toxin (BoNT) injections in the dystonic muscles is the preferred treatment for Cervical Dystonia (CD), but the proper identification of the dystonic muscles remains a challenge. Previous studies showed decreased 8–14 Hz autospectral power in the electromyography (EMG) of splenius muscles in CD patients. Cumulative distribution functions (CDF’s) of dystonic muscles showed increased CDF10 values, representing increased autospectral powers between 3 and 10 Hz, relative to power between 3 and 32 Hz. In this study, we evaluated both methods and investigated the effects of botulinum toxin. Intramuscular EMG recordings were obtained from the splenius, semispinalis, and sternocleidomastoid muscles during standardized isometric tasks in 4 BoNT-naïve CD patients, 12 BoNT-treated patients, and 8 healthy controls. BoNT-treated patients were measured 4–7 weeks after their last BoNT injections and again after 11–15 weeks. We found significantly decreased 8–14 Hz autospectral power in splenius muscles, but not in the semispinalis and sternocleidomastoid muscles of CD patients when compared to healthy controls. CDF10 analysis was superior in demonstrating subtle autospectral changes, and showed increased CDF10 values in all studied muscles of CD patients. These results did not change significantly after BoNT injections. Further studies are needed to investigate the origin of these autospectral changes in dystonia patients, and to assess their potential in muscle selection for BoNT treatment. Full article
(This article belongs to the Special Issue Muscle Selection for BoNT)
Figures

Figure 1a

Open AccessCommunication The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study
Toxins 2017, 9(9), 258; doi:10.3390/toxins9090258
Received: 28 April 2017 / Revised: 27 July 2017 / Accepted: 22 August 2017 / Published: 24 August 2017
PDF Full-text (5611 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects
[...] Read more.
Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced activity against malignant cells, we detected decreased tumor volumes and weights in beauvericin-treated mice compared to controls in both the allo- and the xenograft model without any adverse effects. No significant differences were detected concerning percentages of proliferating and mitotic cells in tumor sections from treated and untreated mice. However, a significant increase of necrotic areas within whole tumor sections of beauvericin-treated mice was found in both models corresponding to an enhanced number of TUNEL-positive, i.e., apoptotic, cells. Furthermore, moderate beauvericin accumulation was detected in tumor tissues. In conclusion, we suggest beauvericin as a promising novel natural compound for anticancer therapy. Full article
(This article belongs to the Section Mycotoxins)
Figures

Figure 1

Open AccessArticle Heterologous Expression, Purification and Immunoreactivity of the Antigen 5 from Polybia paulista Wasp Venom
Toxins 2017, 9(9), 259; doi:10.3390/toxins9090259
Received: 25 July 2017 / Revised: 15 August 2017 / Accepted: 18 August 2017 / Published: 24 August 2017
PDF Full-text (4504 KB) | HTML Full-text | XML Full-text
Abstract
Polybia paulista (Hymenoptera: Vespidae) is responsible for a high number of sting accidents and anaphylaxis events in Southeast Brazil, Argentina and Paraguay. The specific detection of allergy to the venom of this wasp is often hampered by the lack of recombinant allergens currently
[...] Read more.
Polybia paulista (Hymenoptera: Vespidae) is responsible for a high number of sting accidents and anaphylaxis events in Southeast Brazil, Argentina and Paraguay. The specific detection of allergy to the venom of this wasp is often hampered by the lack of recombinant allergens currently available for molecular diagnosis. Antigen 5 (~23 kDa) from P. paulista venom (Poly p 5) is a highly abundant and glycosylated allergenic protein that could be used for development of component-resolved diagnosis (CRD). Here, we describe the cloning and heterologous expression of the antigen 5 (rPoly p 5) from P. paulista venom using the eukaryotic system Pichia pastoris. The expression as a secreted protein yielded high levels of soluble rPoly p 5. The recombinant allergen was further purified to homogeneity (99%) using a two-step chromatographic procedure. Simultaneously, the native form of the allergen (nPoly p 5) was purified from the wasp venom by Ion exchange chromatography. The rPoly p 5 and nPoly p 5 were then submitted to a comparative analysis of IgE-mediated immunodetection using sera from patients previously diagnosed with sensitization to wasp venoms. Both rPoly p 5 and nPoly p 5 were recognized by specific IgE (sIgE) in the sera of the allergic individuals. The high levels of identity found between nPoly p 5 and rPoly p 5 by the alignment of its primary sequences as well as by 3-D models support the results obtained in the immunoblot. Overall, we showed that P. pastoris is a suitable system for production of soluble rPoly p 5 and that the recombinant allergen represents a potential candidate for molecular diagnosis of P.paulista venom allergy. Full article
(This article belongs to the Section Animal Venoms)
Figures

Open AccessArticle Orally Delivered Scorpion Antimicrobial Peptides Exhibit Activity against Pea Aphid (Acyrthosiphon pisum) and Its Bacterial Symbionts
Toxins 2017, 9(9), 261; doi:10.3390/toxins9090261
Received: 4 July 2017 / Revised: 3 August 2017 / Accepted: 22 August 2017 / Published: 24 August 2017
PDF Full-text (3239 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aphids are severe agricultural pests that damage crops by feeding on phloem sap and vectoring plant pathogens. Chemical insecticides provide an important aphid control strategy, but alternative and sustainable control measures are required to avoid rapidly emerging resistance, environmental contamination, and the risk
[...] Read more.
Aphids are severe agricultural pests that damage crops by feeding on phloem sap and vectoring plant pathogens. Chemical insecticides provide an important aphid control strategy, but alternative and sustainable control measures are required to avoid rapidly emerging resistance, environmental contamination, and the risk to humans and beneficial organisms. Aphids are dependent on bacterial symbionts, which enable them to survive on phloem sap lacking essential nutrients, as well as conferring environmental stress tolerance and resistance to parasites. The evolution of aphids has been accompanied by the loss of many immunity-related genes, such as those encoding antibacterial peptides, which are prevalent in other insects, probably because any harm to the bacterial symbionts would inevitably affect the aphids themselves. This suggests that antimicrobial peptides (AMPs) could replace or at least complement conventional insecticides for aphid control. We fed the pea aphids (Acyrthosiphon pisum) with AMPs from the venom glands of scorpions. The AMPs reduced aphid survival, delayed their reproduction, displayed in vitro activity against aphid bacterial symbionts, and reduced the number of symbionts in vivo. Remarkably, we found that some of the scorpion AMPs compromised the aphid bacteriome, a specialized organ that harbours bacterial symbionts. Our data suggest that scorpion AMPs holds the potential to be developed as bio-insecticides, and are promising candidates for the engineering of aphid-resistant crops. Full article
(This article belongs to the Section Animal Venoms)
Figures

Figure 1

Open AccessArticle Disease Modifying Effects of the Spider Toxin Parawixin2 in the Experimental Epilepsy Model
Toxins 2017, 9(9), 262; doi:10.3390/toxins9090262
Received: 12 January 2017 / Revised: 27 April 2017 / Accepted: 18 August 2017 / Published: 25 August 2017
PDF Full-text (6776 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(1) Background: Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. It is also the one with the highest percentage of drug-resistance to the current available anti-epileptic drugs (AED). Additionaly, most antiepileptic drugs are only able to control seizures
[...] Read more.
(1) Background: Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. It is also the one with the highest percentage of drug-resistance to the current available anti-epileptic drugs (AED). Additionaly, most antiepileptic drugs are only able to control seizures in epileptogenesis, but do not decrease the hippocampal neurodegenerative process. TLE patients have a reduced population of interneuronal cells, which express Parvalbumin (PV) proteins. This reduction is directly linked to seizure frequency and severity in the chronic period of epilepsy. There is therefore a need to seek new therapies with a disease-modifying profile, and with efficient antiepileptic and neuroprotective properties. Parawixin2, a compound isolated from the venom of the spider Parawixia bistriata, has been shown to inhibit GABA transporters (GAT) and to have acute anticonvulsant effects in rats. (2) Methods: In this work, we studied the effects of Parawixin2 and Tiagabine (an FDA- approved GAT inhibitor), and compared these effects in a TLE model. Rats were subjected to lithium-pilocarpine TLE model and the main features were evaluated over a chronic period including: (a) spontaneous recurrent seizures (SRS), (b) neuronal loss, and (c) PV cell density in different regions of the hippocampus (CA1, CA3, DG and Hilus). (3) Results: Parawixin2 treatment reduced SRS frequency whereas Tiagabine did not. We also found a significant reduction in neuronal loss in CA3 and in the hilus regions of the hippocampus, in animals treated with Parawixin2. Noteworthy, Parawixin2 significantly reversed PV cell loss observed particularly in DG layers. (4) Conclusions: Parawixin2 exerts a promising neuroprotective and anti-epileptic effect and has potential as a novel agent in drug design. Full article
(This article belongs to the Section Animal Venoms)
Figures

Figure 1

Open AccessArticle Reduced Enterotoxin D Formation on Boiled Ham in Staphylococcus aureus Δagr Mutant
Toxins 2017, 9(9), 263; doi:10.3390/toxins9090263
Received: 4 August 2017 / Revised: 21 August 2017 / Accepted: 24 August 2017 / Published: 25 August 2017
PDF Full-text (786 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcal food poisoning (SFP) is a common cause of foodborne illness worldwide, and enterotoxin D (SED) is one of the most frequent Staphylococcus aureus enterotoxins associated with it. It has been reported that the expression and formation of SED in S. aureus is
[...] Read more.
Staphylococcal food poisoning (SFP) is a common cause of foodborne illness worldwide, and enterotoxin D (SED) is one of the most frequent Staphylococcus aureus enterotoxins associated with it. It has been reported that the expression and formation of SED in S. aureus is regulated by the quorum sensing Agr system. In this study, the effect of agr deletion on sed expression in S. aureus grown on boiled ham was investigated. Growth, sed mRNA and SED protein levels in an S. aureus wild type strain and its isogenic Δagr mutant were monitored for 14 days at 22 °C. The results showed that although deletion of the agr gene did not affect the growth rate or maximum cell density of S. aureus on boiled ham, it had a pronounced effect on SED formation during the first 5 days of incubation. The SED concentration was not reflected in the amount of preceding sed transcripts, suggesting that sed transcription levels may not always reflect SED formation. The expression of RNAIII transcript, the regulatory signal of the Agr system, was also monitored. Similar transcription patterns were observed for RNAIII and sed. Surprisingly, in the Δagr mutant, sed expression was comparable to that in the wild type strain, and was thus unaffected by deletion of the Agr system. These results demonstrate that the Agr system appears to only partially affect SED formation, even in a real food environment. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
Figures

Figure 1

Open AccessArticle Sinapic Acid Affects Phenolic and Trichothecene Profiles of F. culmorum and F. graminearum Sensu Stricto
Toxins 2017, 9(9), 264; doi:10.3390/toxins9090264
Received: 8 August 2017 / Revised: 18 August 2017 / Accepted: 24 August 2017 / Published: 28 August 2017
PDF Full-text (544 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plant-derived compounds for reducing the mycotoxin load in food and feed have become a rapidly developing research field of importance for plant breeding efforts and in the search for natural fungicides. In this study, toxigenic strains of Fusarium culmorum and F. graminearum sensu
[...] Read more.
Plant-derived compounds for reducing the mycotoxin load in food and feed have become a rapidly developing research field of importance for plant breeding efforts and in the search for natural fungicides. In this study, toxigenic strains of Fusarium culmorum and F. graminearum sensu stricto were exposed to sinapic acid on solid YES media at levels close to those reported in wheat bran. Fusaria produced phenolic acids, whose accumulation was decreased by exogenous sinapic acid. Strains exposed to the lowest doses of sinapic acid showed more efficient reduction of phenolic acid production than fungi kept at higher concentrations of this compound. Fungi reduced exogenous sinapic acid, leading to the formation of syringic aldehyde. Treatment with sinapic acid led to a dramatic accumulation of its parent compound ferulic acid, presumably due to inhibition of the further conversion of this phenolic compound. Exogenous sinapic acid decreased the production of trichothecenes by fungi. Higher doses of sinapic acid resulted in more efficient reduction of mycotoxin accumulation in the media. Gene expression studies of Tri genes responsible for trichothecene biosynthesis (Tri4, Tri5 and Tri10) proved that the inhibition of mycotoxin production by sinapic acid occurred at the transcriptional level. Fusaria respond to sinapic acid by stimulation of ergosterol biosynthesis. Full article
(This article belongs to the collection Fusarium Toxins – Relevance for Human and Animal Health)
Figures

Figure 1

Open AccessArticle High Throughput Identification of Antimicrobial Peptides from Fish Gastrointestinal Microbiota
Toxins 2017, 9(9), 266; doi:10.3390/toxins9090266
Received: 10 August 2017 / Revised: 25 August 2017 / Accepted: 28 August 2017 / Published: 30 August 2017
PDF Full-text (10587 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antimicrobial peptides (AMPs) are a group of small peptides, which are secreted by almost all creatures in nature. They have been explored in therapeutic and agricultural aspects as they are toxic to many bacteria. A considerable amount of work has been conducted in
[...] Read more.
Antimicrobial peptides (AMPs) are a group of small peptides, which are secreted by almost all creatures in nature. They have been explored in therapeutic and agricultural aspects as they are toxic to many bacteria. A considerable amount of work has been conducted in analyzing 16S and metagenomics of the gastrointestinal (GI) microbiome of grass carp (Ctenopharyngodon idellus). However, these datasets are still untapped resources. In this present study, a homologous search was performed to predict AMPs from our newly generated metagenome of grass carp. We identified five AMPs with high similarities to previously reported bacterial toxins, such as lantibiotic and class II bacteriocins. In addition, we observed that the top abundant genus in the GI microbiota of the grass carp was generally consistent with the putative AMP-producing strains, which are mainly from Lactobacillales. Furthermore, we constructed the phylogenetic relationship of these putative AMP-producing bacteria existing in the GI of grass carp and some popular commercial probiotics (commonly used for microecologics), demonstrating that they are closely related. Thus, these strains have the potential to be developed into novel microecologics. In a word, we provide a high-throughput way to discover AMPs from fish GI microbiota, which can be developed as alternative pathogen antagonists (toxins) for microecologics or probiotic supplements. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle Recombinant Botulinum Neurotoxin Hc Subunit (BoNT Hc) and Catalytically Inactive Clostridium botulinum Holoproteins (ciBoNT HPs) as Vaccine Candidates for the Prevention of Botulism
Toxins 2017, 9(9), 269; doi:10.3390/toxins9090269
Received: 19 July 2017 / Revised: 29 August 2017 / Accepted: 30 August 2017 / Published: 3 September 2017
PDF Full-text (915 KB) | HTML Full-text | XML Full-text
Abstract
There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering
[...] Read more.
There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering have resulted in subsequent vaccine efforts being primarily focused on the production of highly purified recombinant protein antigens representing one or more domains of the botulinum neurotoxin. Recombinant subunit vaccines based on the carboxy one-third of the toxin (Hc) developed in our lab against serotypes A-F have been shown to be safe and effective. However, in response to the identification of an ever increasing number of BoNT subtypes with significant amino acid heterogeneity, we have developed catalytically inactive BoNT holoproteins (ciBoNT HPs) in an attempt to elicit greater protective immunity to address these toxin variants. Here we report the production of ciBoNT/B1 HP, ciBoNT/C1 HP, ciBoNT/E1 HP and ciBoNT/F1 HP and compare the immunological and protective abilities of ciBoNT HPs and BoNT/A Hc, BoNT/B Hc, BoNT/C Hc, BoNT/E Hc and BoNT/F Hc vaccines when challenged with homologous and heterologous toxins. Our results suggest the ciBoNT HP vaccines exhibit superior potency after single vaccinations but multiple vaccinations with BoNT/Hc antigens resulted in increased survival rates at the toxin challenge levels used. Full article
(This article belongs to the Special Issue Botulinum Neurotoxins Antibody and Vaccine)
Figures

Figure 1

Open AccessArticle Spread of Tst–Positive Staphylococcus aureus Strains Belonging to ST30 Clone among Patients and Healthcare Workers in Two Intensive Care Units
Toxins 2017, 9(9), 270; doi:10.3390/toxins9090270
Received: 9 August 2017 / Revised: 24 August 2017 / Accepted: 31 August 2017 / Published: 4 September 2017
PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus is a major cause of infections. Toxic shock syndrome toxin (TSST-1) and Panton–Valentine leukocidin (PVL) are associated with severe clinical syndromes. S. aureus colonizing isolates recovered from healthcare workers and patients in the intensive care unit (ICU) of a university hospital
[...] Read more.
Staphylococcus aureus is a major cause of infections. Toxic shock syndrome toxin (TSST-1) and Panton–Valentine leukocidin (PVL) are associated with severe clinical syndromes. S. aureus colonizing isolates recovered from healthcare workers and patients in the intensive care unit (ICU) of a university hospital comprising Group A were compared with those from adult non-ICU carriers (Group B). mecA, lukS/lukF-PV (Panton–Valentine leukocidin, PVL), and tst (toxic shock syndrome toxin) gene carriage was detected by PCR. Clones were identified in all methicillin-resistant S. aureus (MRSA) and toxin-positive methicillin-susceptible strains (MSSA) by pulsed-field gel electrophoresis (PFGE), agr groups, and multi locus sequencing typing (MLST). Group A included 90 S. aureus isolates, whereas Group B 53. PVL was more frequently found among MRSA vs. MSSA (p < 0.001) and in strains of Group B as compared to Group A (p < 0.001), consistent with the spread of ST80-IV. Higher incidence of tst gene carriage was identified among MSSA vs. MRSA (P 0.005) belonging mainly to ST30, and Group A vs. Group B (P 0.002). The wide dissemination of ST80-IV mainly in the community is responsible for a high percentage of PVL-positive MRSA, while silent spread of tst-positive S. aureus clones among ICU patients and personnel poses a threat of hospital transmission and possible severe infections. Full article
(This article belongs to the collection Staphylococcus aureus Toxins)
Figures

Figure 1

Open AccessArticle Benthic Archives Reveal Recurrence and Dominance of Toxigenic Cyanobacteria in a Eutrophic Lake over the Last 220 Years
Toxins 2017, 9(9), 271; doi:10.3390/toxins9090271
Received: 3 August 2017 / Revised: 25 August 2017 / Accepted: 1 September 2017 / Published: 4 September 2017
PDF Full-text (2274 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Akinetes are resistant cells which have the ability to persist in sediment for several decades. We have investigated the temporal distribution of akinetes of two species, Dolichospermum macrosporum and Dolichospermum flos-aquae, in a sediment core sampled in Lake Aydat (France), which covers
[...] Read more.
Akinetes are resistant cells which have the ability to persist in sediment for several decades. We have investigated the temporal distribution of akinetes of two species, Dolichospermum macrosporum and Dolichospermum flos-aquae, in a sediment core sampled in Lake Aydat (France), which covers 220 years. The upper part, from 1907 to 2016, the number of akinetes fluctuated but stayed at high concentrations, especially for D. macrosporum in surface sediment (with the maximal value close to 6.105 akinetes g DW−1 of sediment), suggesting a recurrence of blooms of this species which was probably closely related to anthropic eutrophication since the 1960s. Before 1907, the abundance of akinetes of both species was very low, suggesting only a modest presence of these cyanobacteria. In addition, the percentage of intact akinetes was different for each species, suggesting different ecological processes in the water column. This percentage also decreased with depth, revealing a reduction in germination potential over time. In addition, biosynthetic genes of anatoxin-a (anaC) and microcystin (mcyA) were detected. First results show a high occurrence of mcyA all down the core. In contrast, anaC gene was mostly detected in the surface sediment (since the 1980s), revealing a potentially more recent occurrence of this cyanotoxin in Lake Aydat which may be associated with the recurrence of blooms of D. macrosporum and thus with anthropic activities. Full article
Figures

Figure 1

Open AccessFeature PaperCommunication Use of a Yeast tRNase Killer Toxin to Diagnose Kti12 Motifs Required for tRNA Modification by Elongator
Toxins 2017, 9(9), 272; doi:10.3390/toxins9090272
Received: 31 July 2017 / Revised: 29 August 2017 / Accepted: 3 September 2017 / Published: 5 September 2017
PDF Full-text (5304 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin’s action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence,
[...] Read more.
Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin’s action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g., nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them. Full article
(This article belongs to the Special Issue Yeast Killer Toxins)
Figures

Figure 1

Open AccessArticle Listeriolysin O Regulates the Expression of Optineurin, an Autophagy Adaptor That Inhibits the Growth of Listeria monocytogenes
Toxins 2017, 9(9), 273; doi:10.3390/toxins9090273
Received: 31 July 2017 / Revised: 31 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
PDF Full-text (1820 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Autophagy, a well-established defense mechanism, enables the elimination of intracellular pathogens including Listeria monocytogenes. Host cell recognition results in ubiquitination of L. monocytogenes and interaction with autophagy adaptors p62/SQSTM1 and NDP52, which target bacteria to autophagosomes by binding to microtubule-associated protein
[...] Read more.
Autophagy, a well-established defense mechanism, enables the elimination of intracellular pathogens including Listeria monocytogenes. Host cell recognition results in ubiquitination of L. monocytogenes and interaction with autophagy adaptors p62/SQSTM1 and NDP52, which target bacteria to autophagosomes by binding to microtubule-associated protein 1 light chain 3 (LC3). Although studies have indicated that L. monocytogenes induces autophagy, the significance of this process in the infectious cycle and the mechanisms involved remain poorly understood. Here, we examined the role of the autophagy adaptor optineurin (OPTN), the phosphorylation of which by the TANK binding kinase 1 (TBK1) enhances its affinity for LC3 and promotes autophagosomal degradation, during L. monocytogenes infection. In LC3- and OPTN-depleted host cells, intracellular replicating L. monocytogenes increased, an effect not seen with a mutant lacking the pore-forming toxin listeriolysin O (LLO). LLO induced the production of OPTN. In host cells expressing an inactive TBK1, bacterial replication was also inhibited. Our studies have uncovered an OPTN-dependent pathway in which L. monocytogenes uses LLO to restrict bacterial growth. Hence, manipulation of autophagy by L. monocytogenes, either through induction or evasion, represents a key event in its intracellular life style and could lead to either cytosolic growth or persistence in intracellular vacuolar structures. Full article
(This article belongs to the Special Issue Cellular Entry of Binary and Pore-Forming Bacterial Toxins)
Figures

Open AccessArticle Cobra Venom Factor and Ketoprofen Abolish the Antitumor Effect of Nerve Growth Factor from Cobra Venom
Toxins 2017, 9(9), 274; doi:10.3390/toxins9090274
Received: 17 August 2017 / Revised: 1 September 2017 / Accepted: 2 September 2017 / Published: 6 September 2017
PDF Full-text (3125 KB) | HTML Full-text | XML Full-text
Abstract
We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor
[...] Read more.
We showed recently that nerve growth factor (NGF) from cobra venom inhibited the growth of Ehrlich ascites carcinoma (EAC) inoculated subcutaneously in mice. Here, we studied the influence of anti-complementary cobra venom factor (CVF) and the non-steroidal anti-inflammatory drug ketoprofen on the antitumor NGF effect, as well as on NGF-induced changes in EAC histological patterns, the activity of lactate and succinate dehydrogenases in tumor cells and the serum level of some cytokines. NGF, CVF and ketoprofen reduced the tumor volume by approximately 72%, 68% and 30%, respectively. The antitumor effect of NGF was accompanied by an increase in the lymphocytic infiltration of the tumor tissue, the level of interleukin 1β and tumor necrosis factor α in the serum, as well as the activity of lactate and succinate dehydrogenases in tumor cells. Simultaneous administration of NGF with either CVF or ketoprofen abolished the antitumor effect and reduced all other effects of NGF, whereas NGF itself significantly decreased the antitumor action of both CVF and ketoprofen. Thus, the antitumor effect of NGF critically depended on the status of the immune system and was abolished by the disturbance of the complement system; the disturbance of the inflammatory response canceled the antitumor effect as well. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle Typhonium giganteum Lectin Exerts A Pro-Inflammatory Effect on RAW 264.7 via ROS and The NF-κB Signaling Pathway
Toxins 2017, 9(9), 275; doi:10.3390/toxins9090275
Received: 8 August 2017 / Revised: 4 September 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
PDF Full-text (4087 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Typhonii rhizoma, a widely used herb in traditional Chinese medicine, has acute irritating toxicity related to Typhonium giganteum lectin (TGL). TGL exhibits acute inflammatory effects, but the underlying molecular mechanisms are largely unknown. This paper is designed to assess the pro-inflammatory response
[...] Read more.
Typhonii rhizoma, a widely used herb in traditional Chinese medicine, has acute irritating toxicity related to Typhonium giganteum lectin (TGL). TGL exhibits acute inflammatory effects, but the underlying molecular mechanisms are largely unknown. This paper is designed to assess the pro-inflammatory response of TGL on RAW 264.7 cells. RAW 264.7 treated with 6.25, 12.5, 25, and 50 µg/mL TGL showed elevated levels of inflammatory factors (TNF-α, IL-1β) and of p-IκB and p-p65, all dose-dependent, indicating that TGL had a substantial inflammatory effect and mobilized the nuclear factor-κB (NF-κB) pathway. All four TGL treatments also induced the up-regulation of reactive oxygen species (ROS) and cytosolic free Ca2+ and down-regulation of mitochondrial membrane potential (MMP). The production of cytokines and p-IκB, p-p65 were reduced by N-acetylcysteine (NAC), an ROS scavenger, which somewhat abrogated ROS production. The results showed the TGL-activated inflammatory signaling pathway NF-κB to be associated with the overproduction of ROS. Moreover, 50 μg/mL treatment with TGL led to cell apoptosis after 1 h and increased necrosis over time. These results provided potential molecular mechanisms for the observed inflammatory response to TGL including up-regulation of ROS and cytosolic free Ca2+, down-regulation of MMP, the mobilization of the NF-κB pathway, and the subsequent overproduction of pro-inflammatory factors resulting in apoptosis. Long-term stimulation with TGL resulted in strong toxic effects related to inflammation that induced necrosis in macrophages. Full article
(This article belongs to the Section Plant Toxins)
Figures

Figure 1

Open AccessArticle Total Body Irradiation Mitigates Inflammation and Extends the Therapeutic Time Window for Anti-Ricin Antibody Treatment against Pulmonary Ricinosis in Mice
Toxins 2017, 9(9), 278; doi:10.3390/toxins9090278
Received: 16 August 2017 / Revised: 5 September 2017 / Accepted: 9 September 2017 / Published: 11 September 2017
PDF Full-text (903 KB) | HTML Full-text | XML Full-text
Abstract
Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biowarfare and bioterrorism due to its pronounced toxicity, high availability, and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency
[...] Read more.
Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biowarfare and bioterrorism due to its pronounced toxicity, high availability, and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Massive neutrophil recruitment to the lungs may contribute significantly to ricin-mediated morbidity. In this study, total body irradiation (TBI) served as a non-pharmacological tool to decrease the potential neutrophil-induced lung injury. TBI significantly postponed the time to death of intranasally ricin-intoxicated mice, given that leukopenia remained stable following intoxication. This increase in time to death coincided with a significant reduction in pro-inflammatory marker levels, and led to marked extension of the therapeutic time window for anti-ricin antibody treatment. Full article
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
Figures

Figure 1

Open AccessFeature PaperArticle ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice
Toxins 2017, 9(9), 279; doi:10.3390/toxins9090279
Received: 15 August 2017 / Revised: 31 August 2017 / Accepted: 6 September 2017 / Published: 12 September 2017
PDF Full-text (2186 KB) | HTML Full-text | XML Full-text
Abstract
There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries,
[...] Read more.
There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
Figures

Figure 1

Open AccessArticle α-Conotoxin Decontamination Protocol Evaluation: What Works and What Doesn’t
Toxins 2017, 9(9), 281; doi:10.3390/toxins9090281
Received: 11 August 2017 / Revised: 4 September 2017 / Accepted: 9 September 2017 / Published: 14 September 2017
PDF Full-text (1188 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nine publically available biosafety protocols for safely handling conotoxin peptides were tested to evaluate their decontamination efficacy. Circular dichroism (CD) spectroscopy and mass spectrometry (MS) were used to assess the effect of each chemical treatment on the secondary and primary structure of α-CTx
[...] Read more.
Nine publically available biosafety protocols for safely handling conotoxin peptides were tested to evaluate their decontamination efficacy. Circular dichroism (CD) spectroscopy and mass spectrometry (MS) were used to assess the effect of each chemical treatment on the secondary and primary structure of α-CTx MII (L10V, E11A). Of the nine decontamination methods tested, treatment with 1% (m/v) solution of the enzymatic detergent Contrex™ EZ resulted in a 76.8% decrease in α-helical content as assessed by the mean residue ellipticity at 222 nm, and partial peptide digestion was demonstrated using high performance liquid chromatography mass spectrometry (HPLC-MS). Additionally, treatment with 6% sodium hypochlorite (m/v) resulted in 80.5% decrease in α-helical content and complete digestion of the peptide. The Contrex™ EZ treatment was repeated with three additional α-conotoxins (α-CTxs), α-CTxs LvIA, ImI and PeIA, which verified the decontamination method was reasonably robust. These results support the use of either 1% Contrex™ EZ solution or 6% sodium hypochlorite in biosafety protocols for the decontamination of α-CTxs in research laboratories. Full article
(This article belongs to the collection Marine and Freshwater Toxins)
Figures

Open AccessArticle Zearalenone (ZEN) and Its Influence on Regulation of Gene Expression in Carp (Cyprinus carpio L.) Liver Tissue
Toxins 2017, 9(9), 283; doi:10.3390/toxins9090283
Received: 11 August 2017 / Revised: 7 September 2017 / Accepted: 12 September 2017 / Published: 15 September 2017
PDF Full-text (1085 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Zearalenone (ZEN) is a frequently-occurring mycotoxin in both animal and fish feeds. In order to characterize its effects on carp, three groups of fish were fed for 28 days with feeds contaminated with three different levels of ZEN (low: 332 µg kg−1
[...] Read more.
Zearalenone (ZEN) is a frequently-occurring mycotoxin in both animal and fish feeds. In order to characterize its effects on carp, three groups of fish were fed for 28 days with feeds contaminated with three different levels of ZEN (low: 332 µg kg−1, medium: 621 µg kg−1, and high: 797 µg kg−1 feed). The reversibility of the effects of ZEN was assessed by feeding all of the groups with uncontaminated feed for a further 14 days. Gene expression of immune genes in the liver tissue of the fish was analysed, revealing reduced expressions of immune, antioxidative, and estrogen-related genes after the fish had been exposed to ZEN. However, the expression of vacuole-type H+ ATPase increased substantially with ZEN exposure, thus supporting the previously-reported sensitivity of lysosomal functions to ZEN. Feeding the fish with a ZEN-free diet for a further two weeks changed the effects of ZEN on the expression of some genes, including the expressions of the cytokines IL-1β, IL-8, IL-10, and arginase 2, which were not influenced after four weeks of treatment, but showed lower values after the recovery phase in fish previously treated with ZEN compared with the control group. In summary, this study confirmed the broad effects of ZEN on different essential functions in carp and suggests that the current maximum allowable levels in compound feed are too high to prevent damage to fish. Full article
(This article belongs to the Section Mycotoxins)
Figures

Figure 1

Open AccessArticle Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I)
Toxins 2017, 9(9), 285; doi:10.3390/toxins9090285
Received: 25 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
PDF Full-text (3528 KB) | HTML Full-text | XML Full-text
Abstract
Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic
[...] Read more.
Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic effect of BV in a CPIP model remains unknown. The application of a tight-fitting O-ring around the left ankle for a period of 3 h generated CPIP in C57/Bl6 male adult mice. BV (1 mg/kg ; 1, 2, and 3 times) was administered into the SC layer of the hind paw, and the antiallodynic effects were investigated using the von Frey test and by measuring the expression of neurokinin type 1 (NK-1) receptors in dorsal root ganglia (DRG). The administration of BV dose-dependently reduced the pain withdrawal threshold to mechanical stimuli compared with the pre-administration value and with that of the control group. After the development of the CPIP model, the expression of NK-1 receptors in DRG increased and then decreased following the administration of BV. SC administration of BV results in the attenuation of allodynia in a mouse model of CPIP. The antiallodynic effect was objectively proven through a reduction in the increased expression of NK-1 receptors in DRG. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessArticle A Decrease of Incidence Cases of Fumonisins in South Korean Feedstuff between 2011 and 2016
Toxins 2017, 9(9), 286; doi:10.3390/toxins9090286
Received: 24 August 2017 / Revised: 6 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
PDF Full-text (2780 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several plant pathogen Fusarium species produce fumonisins (FUMs); which can end up in food and feed and; when ingested; can exhibit harmful effects on humans and livestock. Mycotoxin intoxication by fumonisin B1 (FB1) and fumonisin B2 (FB2)
[...] Read more.
Several plant pathogen Fusarium species produce fumonisins (FUMs); which can end up in food and feed and; when ingested; can exhibit harmful effects on humans and livestock. Mycotoxin intoxication by fumonisin B1 (FB1) and fumonisin B2 (FB2) can cause porcine pulmonary edema; leukoencephalomalacia in equines; esophageal cancer and birth defects by natural contamination. Herein; the occurrence of FB1 and FB2 in feedstuff (compound feed and feed ingredients) was investigated between 2011 and 2016 in South Korea. A total of 535 animal feed samples (425 compound feed samples and 110 feed ingredients) produced domestically were sampled four times between 2011 and 2016 (2011; 2012; 2014 and 2016) from feed factories in South Korea. The limit of detection (LOD) for FB1 and FB2 was 20 μg/kg and 25 μg/kg; respectively; and the limit of quantitation (LOQ) was 30 μg/kg and 35 μg/kg; respectively. The recovery range (%) was between 86.4% and 108.8%; and the relative standard deviation (RSD) (%) was 4.7–12.1%. Seven (swine feed samples) out of the 425 feed samples exceeded the European Union (EU) and South Korea commission regulations over the six-year test period; and no feed ingredients exceeded the guidelines. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
Figures

Figure 1

Open AccessArticle The Fungal bZIP Transcription Factor AtfB Controls Virulence-Associated Processes in Aspergillus parasiticus
Toxins 2017, 9(9), 287; doi:10.3390/toxins9090287
Received: 30 July 2017 / Revised: 24 August 2017 / Accepted: 7 September 2017 / Published: 16 September 2017
PDF Full-text (3315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fungal basic leucine zipper (bZIP) transcription factors mediate responses to oxidative stress. The ability to regulate stress response pathways in Aspergillus spp. was postulated to be an important virulence-associated cellular process, because it helps establish infection in humans, plants, and animals. Previous studies
[...] Read more.
Fungal basic leucine zipper (bZIP) transcription factors mediate responses to oxidative stress. The ability to regulate stress response pathways in Aspergillus spp. was postulated to be an important virulence-associated cellular process, because it helps establish infection in humans, plants, and animals. Previous studies have demonstrated that the fungal transcription factor AtfB encodes a protein that is associated with resistance to oxidative stress in asexual conidiospores, and AtfB binds to the promoters of several stress response genes. Here, we conducted a gene silencing of AtfB in Aspergillus parasiticus, a well-characterized fungal pathogen of plants, animals, and humans that produces the secondary metabolite and carcinogen aflatoxin, in order to determine the mechanisms by which AtfB contributes to virulence. We show that AtfB silencing results in a decrease in aflatoxin enzyme levels, the down-regulation of aflatoxin accumulation, and impaired conidiospore development in AtfB-silenced strains. This observation is supported by a decrease of AtfB protein levels, and the down-regulation of many genes in the aflatoxin cluster, as well as genes involved in secondary metabolism and conidiospore development. Global expression analysis (RNA Seq) demonstrated that AtfB functionally links oxidative stress response pathways to a broader and novel subset of target genes involved in cellular defense, as well as in actin and cytoskeleton arrangement/transport. Thus, AtfB regulates the genes involved in development, stress response, and secondary metabolism in A. parasiticus. We propose that the bZIP regulatory circuit controlled by AtfB provides a large number of excellent cellular targets to reduce fungal virulence. More importantly, understanding key players that are crucial to initiate the cellular response to oxidative stress will enable better control over its detrimental impacts on humans. Full article
Figures

Figure 1

Open AccessArticle Evidence for Complex Formation of the Bacillus cereus Haemolysin BL Components in Solution
Toxins 2017, 9(9), 288; doi:10.3390/toxins9090288
Received: 16 August 2017 / Revised: 11 September 2017 / Accepted: 12 September 2017 / Published: 16 September 2017
PDF Full-text (4388 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Haemolysin BL is an important virulence factor regarding the diarrheal type of food poisoning caused by Bacillus cereus. However, the pathogenic importance of this three-component enterotoxin is difficult to access, as nearly all natural B. cereus culture supernatants additionally contain the highly
[...] Read more.
Haemolysin BL is an important virulence factor regarding the diarrheal type of food poisoning caused by Bacillus cereus. However, the pathogenic importance of this three-component enterotoxin is difficult to access, as nearly all natural B. cereus culture supernatants additionally contain the highly cytotoxic Nhe, the second three-component toxin involved in the aetiology of B. cereus-induced food-borne diseases. To better address the toxic properties of the Hbl complex, a system for overexpression and purification of functional, cytotoxic, recombinant (r)Hbl components L2, L1 and B from E. coli was established and an nheABC deletion mutant was constructed from B. cereus reference strain F837/76. Furthermore, 35 hybridoma cell lines producing monoclonal antibodies (mAbs) against Hbl L2, L1 and B were generated. While mAbs 1H9 and 1D8 neutralized Hbl toxicity and thus, represent important tools for future investigations of the mode-of-action of Hbl on the target cell surface, mAb 1D7, in contrast, even enhanced Hbl toxicity by supporting the binding of Hbl B to the cell surface. By using the specific mAbs in Dot blots, indirect and hybrid sandwich enzyme immuno assays (EIAs), complex formation between Hbl L1 and B, as well as L1 and L2 in solution could be shown for the first time. Surface plasmon resonance experiments with the rHbl components confirmed these results with KD values of 4.7 × 10−7 M and 1.5 × 10−7 M, respectively. These findings together with the newly created tools lay the foundation for the detailed elucidation of the molecular mode-of-action of the highly complex three-component Hbl toxin. Full article
(This article belongs to the Special Issue Cellular Entry of Binary and Pore-Forming Bacterial Toxins)
Figures

Figure 1

Open AccessFeature PaperArticle New Insights into the Genome Organization of Yeast Killer Viruses Based on “Atypical” Killer Strains Characterized by High-Throughput Sequencing
Toxins 2017, 9(9), 292; doi:10.3390/toxins9090292
Received: 31 August 2017 / Revised: 15 September 2017 / Accepted: 16 September 2017 / Published: 19 September 2017
PDF Full-text (1870 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used
[...] Read more.
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located around the central poly(A) region. A continuous sequence of the ScV-M2 genome was obtained for the first time. M1 virus was found for the first time in wine yeasts, coexisting with Mbarr-1 virus in T. delbrueckii. Extra 5′- and 3′-sequences were found in all M-genomes. The presence of repeated short sequences in the non-coding 3′-region of most M-genomes indicates that they have a common phylogenetic origin. High identity between amino acid sequences of killer toxins and some unclassified proteins of yeast, bacteria, and wine grapes suggests that killer viruses recruited some sequences from the genome of these organisms, or vice versa, during evolution. Full article
(This article belongs to the Special Issue Yeast Killer Toxins)
Figures

Figure 1

Review

Jump to: Research, Other

Open AccessReview Botulinum Toxin for the Treatment of Neuropathic Pain
Toxins 2017, 9(9), 260; doi:10.3390/toxins9090260
Received: 10 August 2017 / Revised: 18 August 2017 / Accepted: 21 August 2017 / Published: 24 August 2017
PDF Full-text (638 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves
[...] Read more.
Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves inhibiting the release of inflammatory mediators and peripheral neurotransmitters from sensory nerves. Recent journals have demonstrated that BoNT is effective for neuropathic pain, such as postherpetic neuralgia, trigeminal neuralgia, and peripheral neuralgia. The purpose of this review is to summarize the experimental and clinical evidence of the mechanism by which BoNT acts on various types of neuropathic pain and describe why BoNT can be applied as treatment. The PubMed database was searched from 1988 to May 2017. Recent studies have demonstrated that BoNT injections are effective treatments for post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, and intractable neuropathic pain, such as poststroke pain and spinal cord injury. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
Figures

Figure 1

Open AccessReview Structural Features of Apicomplexan Pore-Forming Proteins and Their Roles in Parasite Cell Traversal and Egress
Toxins 2017, 9(9), 265; doi:10.3390/toxins9090265
Received: 2 August 2017 / Revised: 20 August 2017 / Accepted: 22 August 2017 / Published: 29 August 2017
PDF Full-text (3412 KB) | HTML Full-text | XML Full-text
Abstract
Apicomplexan parasites cause diseases, including malaria and toxoplasmosis, in a range of hosts, including humans. These intracellular parasites utilize pore-forming proteins that disrupt host cell membranes to either traverse host cells while migrating through tissues or egress from the parasite-containing vacuole after replication.
[...] Read more.
Apicomplexan parasites cause diseases, including malaria and toxoplasmosis, in a range of hosts, including humans. These intracellular parasites utilize pore-forming proteins that disrupt host cell membranes to either traverse host cells while migrating through tissues or egress from the parasite-containing vacuole after replication. This review highlights recent insight gained from the newly available three-dimensional structures of several known or putative apicomplexan pore-forming proteins that contribute to cell traversal or egress. These new structural advances suggest that parasite pore-forming proteins use distinct mechanisms to disrupt host cell membranes at multiple steps in parasite life cycles. How proteolytic processing, secretion, environment, and the accessibility of lipid receptors regulate the membranolytic activities of such proteins is also discussed. Full article
(This article belongs to the Special Issue Cellular Entry of Binary and Pore-Forming Bacterial Toxins)
Figures

Figure 1

Open AccessReview Vaccines against Botulism
Toxins 2017, 9(9), 268; doi:10.3390/toxins9090268
Received: 8 August 2017 / Revised: 30 August 2017 / Accepted: 30 August 2017 / Published: 2 September 2017
PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used
[...] Read more.
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin. Full article
(This article belongs to the Special Issue Botulinum Neurotoxins Antibody and Vaccine)
Figures

Figure 1

Open AccessReview Bordetella Adenylate Cyclase-Hemolysin Toxins
Toxins 2017, 9(9), 277; doi:10.3390/toxins9090277
Received: 22 August 2017 / Revised: 3 September 2017 / Accepted: 7 September 2017 / Published: 11 September 2017
PDF Full-text (275 KB) | HTML Full-text | XML Full-text
Abstract
Adenylate cyclase-hemolysin toxin is secreted and produced by three classical species of the genus Bordetella: Bordetella pertussis, B. parapertussis and B. bronchiseptica. This toxin has several properties such as: (i) adenylate cyclase activity, enhanced after interaction with the eukaryotic protein,
[...] Read more.
Adenylate cyclase-hemolysin toxin is secreted and produced by three classical species of the genus Bordetella: Bordetella pertussis, B. parapertussis and B. bronchiseptica. This toxin has several properties such as: (i) adenylate cyclase activity, enhanced after interaction with the eukaryotic protein, calmodulin; (ii) a pore-forming activity; (iii) an invasive activity. It plays an important role in the pathogenesis of these Bordetella species responsible for whooping cough in humans or persistent respiratory infections in mammals, by modulating host immune responses. In contrast with other Bordetella toxins or adhesins, lack of (or very low polymorphism) is observed in the structural gene encoding this toxin, supporting its importance as well as a potential role as a vaccine antigen against whooping cough. In this article, an overview of the investigations undertaken on this toxin is presented. Full article
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
Open AccessReview Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?
Toxins 2017, 9(9), 280; doi:10.3390/toxins9090280
Received: 3 August 2017 / Revised: 2 September 2017 / Accepted: 7 September 2017 / Published: 12 September 2017
PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing,
[...] Read more.
Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing, harvesting, and packing, leading to increased colonization as the fruit ripens. Of particular concern are fungal pathogens that not only macerate the host tissue but also secrete significant amounts of mycotoxins. Many studies have described the importance of physiological factors, including stage of fruit development, biochemical factors (ripening, C and N content), and environmental factors (humidity, temperature, water deficit) on the occurrence of mycotoxins. However, those factors usually show a correlative effect on fungal growth and mycotoxin accumulation. Recent reports have suggested that host factors can induce fungal metabolism, leading to the synthesis and accumulation of mycotoxins. This review describes the new vision of host-factor impact on the regulation of mycotoxin biosynthetic gene clusters underlying the complex regulation of mycotoxin accumulation in ripening fruit. Full article
Open AccessFeature PaperReview The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, as a Pharmacological Target in Colorectal Cancer Immunotherapy: A Bench-to-Bedside Current Report
Toxins 2017, 9(9), 282; doi:10.3390/toxins9090282
Received: 15 August 2017 / Revised: 5 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
PDF Full-text (583 KB) | HTML Full-text | XML Full-text
Abstract
Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient
[...] Read more.
Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient population while sparing healthy tissue from damaging autoimmunity. The intestinally restricted receptor guanylyl cyclase C (GUCY2C) is a target that has been investigated for the treatment of colorectal cancer and numerous animal, and clinical studies have demonstrated both efficacy and safety. Here, we describe the current state of GUCY2C-directed cancer immunotherapy and the future directions of this work. Full article
(This article belongs to the Special Issue Heat-Stable Enterotoxins)
Figures

Figure 1

Open AccessReview Worldwide Occurrence and Investigations of Contamination of Herbal Medicines by Tropane Alkaloids
Toxins 2017, 9(9), 284; doi:10.3390/toxins9090284
Received: 7 August 2017 / Revised: 12 September 2017 / Accepted: 14 September 2017 / Published: 15 September 2017
PDF Full-text (434 KB) | HTML Full-text | XML Full-text
Abstract
Tropane alkaloids occur mainly in Solanaceae plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after
[...] Read more.
Tropane alkaloids occur mainly in Solanaceae plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after consumption of any medicinal plant if Solanaceae plants or plant parts are present as contaminants. Globally, almost all reports in 1978–2014 involve herbal teas and one of the prescribed herbs in composite formulae. Contamination most likely occurs during harvest or processing. As for prescribed herbs, on-site inspection is necessary to exclude cross-contamination and accidental mix-up at the retail level. The diagnosis is confirmed by screening for the presence of Solanaceae species and tropane alkaloids. Herbal teas and herbs contaminated by tropane alkaloids can pose a serious health hazard because these relatively heat-stable alkaloids may exist in large quantities. The WHO repeatedly emphasises the importance of good agricultural and collection practices for medicinal plants. DNA barcoding is increasingly used to exclude the presence of contaminants (particularly toxic species) and product substitution. All suspected cases should be reported to health authorities so that investigations along the supply chain and early intervention measures to protect the public can be initiated. Full article
(This article belongs to the collection Toxicity of Natural Alkaloids)
Figures

Figure 1

Open AccessReview Block V RTX Domain of Adenylate Cyclase from Bordetella pertussis: A Conformationally Dynamic Scaffold for Protein Engineering Applications
Toxins 2017, 9(9), 289; doi:10.3390/toxins9090289
Received: 30 August 2017 / Revised: 12 September 2017 / Accepted: 12 September 2017 / Published: 17 September 2017
PDF Full-text (941 KB) | HTML Full-text | XML Full-text
Abstract
The isolated Block V repeats-in-toxin (RTX) peptide domain of adenylate cyclase (CyaA) from Bordetella pertussis reversibly folds into a β-roll secondary structure upon calcium binding. In this review, we discuss how the conformationally dynamic nature of the peptide is being engineered and employed
[...] Read more.
The isolated Block V repeats-in-toxin (RTX) peptide domain of adenylate cyclase (CyaA) from Bordetella pertussis reversibly folds into a β-roll secondary structure upon calcium binding. In this review, we discuss how the conformationally dynamic nature of the peptide is being engineered and employed as a switching mechanism to mediate different protein functions and protein-protein interactions. The peptide has been used as a scaffold for diverse applications including: a precipitation tag for bioseparations, a cross-linking domain for protein hydrogel formation and as an alternative scaffold for biomolecular recognition applications. Proteins and peptides such as the RTX domains that exhibit natural stimulus-responsive behavior are valuable building blocks for emerging synthetic biology applications. Full article
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
Figures

Figure 1

Open AccessReview A Review and Database of Snake Venom Proteomes
Toxins 2017, 9(9), 290; doi:10.3390/toxins9090290
Received: 1 September 2017 / Revised: 15 September 2017 / Accepted: 15 September 2017 / Published: 18 September 2017
PDF Full-text (2615 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the value of this information is increased when it is collated, allowing
[...] Read more.
Advances in the last decade combining transcriptomics with established proteomics methods have made possible rapid identification and quantification of protein families in snake venoms. Although over 100 studies have been published, the value of this information is increased when it is collated, allowing rapid assimilation and evaluation of evolutionary trends, geographical variation, and possible medical implications. This review brings together all compositional studies of snake venom proteomes published in the last decade. Compositional studies were identified for 132 snake species: 42 from 360 (12%) Elapidae (elapids), 20 from 101 (20%) Viperinae (true vipers), 65 from 239 (27%) Crotalinae (pit vipers), and five species of non-front-fanged snakes. Approximately 90% of their total venom composition consisted of eight protein families for elapids, 11 protein families for viperines and ten protein families for crotalines. There were four dominant protein families: phospholipase A2s (the most common across all front-fanged snakes), metalloproteases, serine proteases and three-finger toxins. There were six secondary protein families: cysteine-rich secretory proteins, l-amino acid oxidases, kunitz peptides, C-type lectins/snaclecs, disintegrins and natriuretic peptides. Elapid venoms contained mostly three-finger toxins and phospholipase A2s and viper venoms metalloproteases, phospholipase A2s and serine proteases. Although 63 protein families were identified, more than half were present in <5% of snake species studied and always in low abundance. The importance of these minor component proteins remains unknown. Full article
(This article belongs to the Section Animal Venoms)
Figures

Open AccessReview Shiga Toxin Therapeutics: Beyond Neutralization
Toxins 2017, 9(9), 291; doi:10.3390/toxins9090291
Received: 25 August 2017 / Revised: 15 September 2017 / Accepted: 15 September 2017 / Published: 19 September 2017
PDF Full-text (1228 KB) | HTML Full-text | XML Full-text
Abstract
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal
[...] Read more.
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells. The preclinical development of toxin-targeted HUS therapies has been hindered by the sporadic, geographically dispersed nature of STEC outbreaks with HUS cases and the limited financial incentive for the commercial development of therapies for an acute disease with an inconsistent patient population. The following review considers potential therapeutic targeting of the downstream cellular impacts of Shiga toxicity, which include the unfolded protein response (UPR) and the ribotoxic stress response (RSR). Outcomes of the UPR and RSR are relevant to other diseases with large global incidence and prevalence rates, thus reducing barriers to the development of commercial drugs that could improve STEC and HUS patient outcomes. Full article
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
Figures

Figure 1

Other

Jump to: Research, Review

Open AccessObituary Remembering Dr. Rex Munday
Toxins 2017, 9(9), 257; doi:10.3390/toxins9090257
Received: 18 August 2017 / Revised: 21 August 2017 / Accepted: 21 August 2017 / Published: 24 August 2017
PDF Full-text (726 KB) | HTML Full-text | XML Full-text
Abstract
Rex Munday was a scientist working for AgResearch Ltd. in New Zealand. He was a leading figure in the area of marine toxin toxicity. His passing in July 2017 marked a loss for his family, as well as for colleagues who knew him
[...] Read more.
Rex Munday was a scientist working for AgResearch Ltd. in New Zealand. He was a leading figure in the area of marine toxin toxicity. His passing in July 2017 marked a loss for his family, as well as for colleagues who knew him as a dedicated professional, and a lively scientist with a great sense of humor. Full article
Figures

Figure 1

Open AccessCase Report Recreational Exposure during Algal Bloom in Carrasco Beach, Uruguay: A Liver Failure Case Report
Toxins 2017, 9(9), 267; doi:10.3390/toxins9090267
Received: 1 August 2017 / Revised: 24 August 2017 / Accepted: 24 August 2017 / Published: 31 August 2017
PDF Full-text (10195 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure
[...] Read more.
In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child’s case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II–III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr−1 tissue) and [D-Leu1]MC-LR (75.4 ng·gr−1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis. Full article
(This article belongs to the Special Issue Selected Papers from the 5th Iberoamerican Cyanotoxins Meeting)
Figures

Figure 1

Open AccessMeeting Report Report from the 1st MYCOKEY International Conference Global Mycotoxin Reduction in the Food and Feed Chain Held in Ghent, Belgium, 11–14 September 2017
Toxins 2017, 9(9), 276; doi:10.3390/toxins9090276
Received: 31 August 2017 / Revised: 1 September 2017 / Accepted: 1 September 2017 / Published: 8 September 2017
PDF Full-text (1241 KB) | HTML Full-text | XML Full-text
Abstract
This conference is organized within the framework of the H2020—Research and Innovation Action—Societal Challenge 2—“Food security, sustainable agriculture and forestry, marine, maritime and inland water research and the bioeconomy challenge”—GA 678781 MycoKey “Integrated and innovative key actions for mycotoxin management in the food
[...] Read more.
This conference is organized within the framework of the H2020—Research and Innovation Action—Societal Challenge 2—“Food security, sustainable agriculture and forestry, marine, maritime and inland water research and the bioeconomy challenge”—GA 678781 MycoKey “Integrated and innovative key actions for mycotoxin management in the food and feed chain” [...]
Full article

Journal Contact

MDPI AG
Toxins Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
E-Mail: 
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Toxins Edit a special issue Review for Toxins
logo
loading...
Back to Top