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Toxins, Volume 6, Issue 6 (June 2014), Pages 1696-1950

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Research

Jump to: Review

Open AccessArticle Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure
Toxins 2014, 6(6), 1724-1741; doi:10.3390/toxins6061724
Received: 6 February 2014 / Revised: 7 May 2014 / Accepted: 20 May 2014 / Published: 30 May 2014
Cited by 4 | PDF Full-text (553 KB) | HTML Full-text | XML Full-text
Abstract
Toxic shock syndrome (TSS) results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs [...] Read more.
Toxic shock syndrome (TSS) results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs). There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days) lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1) neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation), determination of IL-2 release in the cell supernatant (ELISA), and IL-2 gene activation (real-time PCR (RT-PCR)). Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure. Full article
Open AccessArticle Differential Effects of Indoxyl Sulfate and Inorganic Phosphate in a Murine Cerebral Endothelial Cell Line (bEnd.3)
Toxins 2014, 6(6), 1742-1760; doi:10.3390/toxins6061742
Received: 4 April 2014 / Revised: 17 May 2014 / Accepted: 26 May 2014 / Published: 4 June 2014
Cited by 4 | PDF Full-text (1352 KB) | HTML Full-text | XML Full-text
Abstract
Endothelial dysfunction plays a key role in stroke in chronic kidney disease patients. To explore the underlying mechanisms, we evaluated the effects of two uremic toxins on cerebral endothelium function. bEnd.3 cells were exposed to indoxyl sulfate (IS) and inorganic phosphate (Pi). [...] Read more.
Endothelial dysfunction plays a key role in stroke in chronic kidney disease patients. To explore the underlying mechanisms, we evaluated the effects of two uremic toxins on cerebral endothelium function. bEnd.3 cells were exposed to indoxyl sulfate (IS) and inorganic phosphate (Pi). Nitric oxide (NO), reactive oxygen species (ROS) and O2 were measured using specific fluorophores. Peroxynitrite and eNOS uncoupling were evaluated using ebselen, a peroxide scavenger, and tetrahydrobiopterin (BH4), respectively. Cell viability decreased after IS or Pi treatment (p < 0.01). Both toxins reduced NO production (IS, p < 0.05; Pi, p < 0.001) and induced ROS production (p < 0.001). IS and 2 mM Pi reduced O2 production (p < 0.001). Antioxidant pretreatment reduced ROS levels in both IS- and Pi-treated cells, but a more marked reduction of O2 production was observed in Pi-treated cells (p < 0.001). Ebselen reduced the ROS production induced by the two toxins (p < 0.001); suggesting a role of peroxynitrite in this process. BH4 addition significantly reduced O2 and increased NO production in Pi-treated cells (p < 0.001), suggesting eNOS uncoupling, but had no effect in IS-treated cells. This study shows, for the first time, that IS and Pi induce cerebral endothelial dysfunction by decreasing NO levels due to enhanced oxidative stress. However, Pi appears to be more deleterious, as it also induces eNOS uncoupling. Full article
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Open AccessArticle Further Insights into Brevetoxin Metabolism by de Novo Radiolabeling
Toxins 2014, 6(6), 1785-1798; doi:10.3390/toxins6061785
Received: 6 April 2014 / Revised: 23 May 2014 / Accepted: 27 May 2014 / Published: 10 June 2014
Cited by 2 | PDF Full-text (1210 KB) | HTML Full-text | XML Full-text
Abstract
The toxic dinoflagellate Karenia brevis, responsible for early harmful algal blooms in the Gulf of Mexico, produces many secondary metabolites, including potent neurotoxins called brevetoxins (PbTx). These compounds have been identified as toxic agents for humans, and they are also responsible [...] Read more.
The toxic dinoflagellate Karenia brevis, responsible for early harmful algal blooms in the Gulf of Mexico, produces many secondary metabolites, including potent neurotoxins called brevetoxins (PbTx). These compounds have been identified as toxic agents for humans, and they are also responsible for the deaths of several marine organisms. The overall biosynthesis of these highly complex metabolites has not been fully ascertained, even if there is little doubt on a polyketide origin. In addition to gaining some insights into the metabolic events involved in the biosynthesis of these compounds, feeding studies with labeled precursors helps to discriminate between the de novo biosynthesis of toxins and conversion of stored intermediates into final toxic products in the response to environmental stresses. In this context, the use of radiolabeled precursors is well suited as it allows working with the highest sensitive techniques and consequently with a minor amount of cultured dinoflagellates. We were then able to incorporate [U-14C]-acetate, the renowned precursor of the polyketide pathway, in several PbTx produced by K. brevis. The specific activities of PbTx-1, -2, -3, and -7, identified by High-Resolution Electrospray Ionization Mass Spectrometer (HRESIMS), were assessed by HPLC-UV and highly sensitive Radio-TLC counting. We demonstrated that working at close to natural concentrations of acetate is a requirement for biosynthetic studies, highlighting the importance of highly sensitive radiolabeling feeding experiments. Quantification of the specific activity of the four, targeted toxins led us to propose that PbTx-1 and PbTx-2 aldehydes originate from oxidation of the primary alcohols of PbTx-7 and PbTx-3, respectively. This approach will open the way for a better comprehension of the metabolic pathways leading to PbTx but also to a better understanding of their regulation by environmental factors. Full article
(This article belongs to the collection Marine and Freshwater Toxins)
Open AccessArticle Microcystins Alter Chemotactic Behavior in Caenorhabditis elegans by Selectively Targeting the AWA Sensory Neuron
Toxins 2014, 6(6), 1813-1836; doi:10.3390/toxins6061813
Received: 28 January 2014 / Revised: 17 May 2014 / Accepted: 28 May 2014 / Published: 10 June 2014
Cited by 3 | PDF Full-text (1399 KB) | HTML Full-text | XML Full-text
Abstract
Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model [...] Read more.
Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition. Full article
(This article belongs to the Special Issue Neurotoxins: Health Threats and Biological Tools)
Open AccessArticle Exposure of Lycopersicon Esculentum to Microcystin-LR: Effects in the Leaf Proteome and Toxin Translocation from Water to Leaves and Fruits
Toxins 2014, 6(6), 1837-1854; doi:10.3390/toxins6061837
Received: 26 March 2014 / Revised: 30 May 2014 / Accepted: 3 June 2014 / Published: 11 June 2014
Cited by 5 | PDF Full-text (990 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Natural toxins such as those produced by freshwater cyanobacteria have been regarded as an emergent environmental threat. However, the impact of these water contaminants in agriculture is not yet fully understood. The aim of this work was to investigate microcystin-LR (MC-LR) toxicity [...] Read more.
Natural toxins such as those produced by freshwater cyanobacteria have been regarded as an emergent environmental threat. However, the impact of these water contaminants in agriculture is not yet fully understood. The aim of this work was to investigate microcystin-LR (MC-LR) toxicity in Lycopersicon esculentum and the toxin accumulation in this horticultural crop. Adult plants (2 month-old) grown in a greenhouse environment were exposed for 2 weeks to either pure MC-LR (100 μg/L) or Microcystis aeruginosa crude extracts containing 100 μg/L MC-LR. Chlorophyll fluorescence was measured, leaf proteome investigated with two-dimensional gel electrophoresis and Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF)/TOF, and toxin bioaccumulation assessed by liquid chromatography-mass spectrometry (LC-MS)/MS. Variations in several protein markers (ATP synthase subunits, Cytochrome b6-f complex iron-sulfur, oxygen-evolving enhancer proteins) highlight the decrease of the capacity of plants to synthesize ATP and to perform photosynthesis, whereas variations in other proteins (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit and ribose-5-phosphate isomerase) suggest an increase of carbon fixation and decrease of carbohydrate metabolism reactions in plants exposed to pure MC-LR and cyanobacterial extracts, respectively. MC-LR was found in roots (1635.21 μg/kg fw), green tomatoes (5.15–5.41 μg/kg fw), mature tomatoes (10.52–10.83 μg/kg fw), and leaves (12,298.18 μg/kg fw). The results raise concerns relative to food safety and point to the necessity of monitoring the bioaccumulation of water toxins in agricultural systems affected by cyanotoxin contamination. Full article
(This article belongs to the Special Issue Genomics and Proteomics of Cyanotoxins)
Open AccessArticle A High-Throughput, Precipitating Colorimetric Sandwich ELISA Microarray for Shiga Toxins
Toxins 2014, 6(6), 1855-1872; doi:10.3390/toxins6061855
Received: 18 April 2014 / Revised: 30 May 2014 / Accepted: 3 June 2014 / Published: 11 June 2014
Cited by 1 | PDF Full-text (1397 KB) | HTML Full-text | XML Full-text
Abstract
Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC) bacteria were simultaneously detected with a newly developed, high-throughput antibody microarray platform. The proteinaceous toxins were immobilized and sandwiched between biorecognition elements (monoclonal antibodies) and pooled horseradish peroxidase [...] Read more.
Shiga toxins 1 and 2 (Stx1 and Stx2) from Shiga toxin-producing E. coli (STEC) bacteria were simultaneously detected with a newly developed, high-throughput antibody microarray platform. The proteinaceous toxins were immobilized and sandwiched between biorecognition elements (monoclonal antibodies) and pooled horseradish peroxidase (HRP)-conjugated monoclonal antibodies. Following the reaction of HRP with the precipitating chromogenic substrate (metal enhanced 3,3-diaminobenzidine tetrahydrochloride or DAB), the formation of a colored product was quantitatively measured with an inexpensive flatbed page scanner. The colorimetric ELISA microarray was demonstrated to detect Stx1 and Stx2 at levels as low as ~4.5 ng/mL within ~2 h of total assay time with a narrow linear dynamic range of ~1–2 orders of magnitude and saturation levels well above background. Stx1 and/or Stx2 produced by various strains of STEC were also detected following the treatment of cultured cells with mitomycin C (a toxin-inducing antibiotic) and/or B-PER (a cell-disrupting, protein extraction reagent). Semi-quantitative detection of Shiga toxins was demonstrated to be sporadic among various STEC strains following incubation with mitomycin C; however, further reaction with B-PER generally resulted in the detection of or increased detection of Stx1, relative to Stx2, produced by STECs inoculated into either axenic broth culture or culture broth containing ground beef. Full article
(This article belongs to the Special Issue Advances in Toxin Detection)
Open AccessArticle Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes
Toxins 2014, 6(6), 1873-1881; doi:10.3390/toxins6061873
Received: 6 May 2014 / Revised: 26 May 2014 / Accepted: 27 May 2014 / Published: 12 June 2014
Cited by 3 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text
Abstract
Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings [...] Read more.
Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms. Full article
(This article belongs to the Section Animal Venoms)
Open AccessArticle Cloning and Characterization of a Unique Cytotoxic Protein Parasporin-5 Produced by Bacillus thuringiensis A1100 Strain
Toxins 2014, 6(6), 1882-1895; doi:10.3390/toxins6061882
Received: 28 April 2014 / Revised: 29 May 2014 / Accepted: 9 June 2014 / Published: 18 June 2014
Cited by 5 | PDF Full-text (382 KB) | HTML Full-text | XML Full-text
Abstract
Parasporin is the cytocidal protein present in the parasporal inclusion of the non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity but has cytocidal activities, preferentially killing cancer cells. In this study, we characterized a cytocidal protein that belongs to this category, [...] Read more.
Parasporin is the cytocidal protein present in the parasporal inclusion of the non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity but has cytocidal activities, preferentially killing cancer cells. In this study, we characterized a cytocidal protein that belongs to this category, which was designated parasporin-5 (PS5). PS5 was purified from B. thuringiensis serovar tohokuensis strain A1100 based on its cytocidal activity against human leukemic T cells (MOLT-4). The 50% effective concentration (EC50) of PS5 to MOLT-4 cells was approximately 0.075 μg/mL. PS5 was expressed as a 33.8-kDa inactive precursor protein and exhibited cytocidal activity only when degraded by protease at the C-terminal into smaller molecules of 29.8 kDa. Although PS5 showed no significant homology with other known parasporins, a Position Specific Iterative-Basic Local Alignment Search Tool (PSI-BLAST) search revealed that the protein showed slight homology to, not only some B. thuringiensis Cry toxins, but also to aerolysin-type β-pore-forming toxins (β-PFTs). The recombinant PS5 protein could be obtained as an active protein only when it was expressed in a precursor followed by processing with proteinase K. The cytotoxic activities of the protein against various mammalian cell lines were evaluated. PS5 showed strong cytocidal activity to seven of 18 mammalian cell lines tested, and low to no cytotoxicity to the others. Full article
(This article belongs to the Special Issue <i>Bacillus thuringiensis</i> Toxins)
Open AccessArticle Impact of Nitrogen Sources on Gene Expression and Toxin Production in the Diazotroph Cylindrospermopsis raciborskii CS-505 and Non-Diazotroph Raphidiopsis brookii D9
Toxins 2014, 6(6), 1896-1915; doi:10.3390/toxins6061896
Received: 1 May 2014 / Revised: 31 May 2014 / Accepted: 9 June 2014 / Published: 20 June 2014
Cited by 10 | PDF Full-text (1136 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Different environmental nitrogen sources play selective roles in the development of cyanobacterial blooms and noxious effects are often exacerbated when toxic cyanobacteria are dominant. Cylindrospermopsis raciborskii CS-505 (heterocystous, nitrogen fixing) and Raphidiopsis brookii D9 (non-N2 fixing) produce the nitrogenous toxins cylindrospermopsin [...] Read more.
Different environmental nitrogen sources play selective roles in the development of cyanobacterial blooms and noxious effects are often exacerbated when toxic cyanobacteria are dominant. Cylindrospermopsis raciborskii CS-505 (heterocystous, nitrogen fixing) and Raphidiopsis brookii D9 (non-N2 fixing) produce the nitrogenous toxins cylindrospermopsin (CYN) and paralytic shellfish toxins (PSTs), respectively. These toxin groups are biosynthesized constitutively by two independent putative gene clusters, whose flanking genes are target for nitrogen (N) regulation. It is not yet known how or if toxin biosynthetic genes are regulated, particularly by N-source dependency. Here we show that binding boxes for NtcA, the master regulator of N metabolism, are located within both gene clusters as potential regulators of toxin biosynthesis. Quantification of intra- and extracellular toxin content in cultures at early stages of growth under nitrate, ammonium, urea and N-free media showed that N-sources influence neither CYN nor PST production. However, CYN and PST profiles were altered under N-free medium resulting in a decrease in the predicted precursor toxins (doCYN and STX, respectively). Reduced STX amounts were also observed under growth in ammonium. Quantification of toxin biosynthesis and transport gene transcripts revealed a constitutive transcription under all tested N-sources. Our data support the hypothesis that PSTs and CYN are constitutive metabolites whose biosynthesis is correlated to cyanobacterial growth rather than directly to specific environmental conditions. Overall, the constant biosynthesis of toxins and expression of the putative toxin-biosynthesis genes supports the usage of qPCR probes in water quality monitoring of toxic cyanobacteria. Full article
(This article belongs to the Special Issue Genomics and Proteomics of Cyanotoxins)
Open AccessCommunication Comparison of Expression of Secondary Metabolite Biosynthesis Cluster Genes in Aspergillus flavus, A. parasiticus, and A. oryzae
Toxins 2014, 6(6), 1916-1928; doi:10.3390/toxins6061916
Received: 21 March 2014 / Revised: 9 June 2014 / Accepted: 13 June 2014 / Published: 23 June 2014
Cited by 7 | PDF Full-text (675 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fifty six secondary metabolite biosynthesis gene clusters are predicted to be in the Aspergillus flavus genome. In spite of this, the biosyntheses of only seven metabolites, including the aflatoxins, kojic acid, cyclopiazonic acid and aflatrem, have been assigned to a particular gene [...] Read more.
Fifty six secondary metabolite biosynthesis gene clusters are predicted to be in the Aspergillus flavus genome. In spite of this, the biosyntheses of only seven metabolites, including the aflatoxins, kojic acid, cyclopiazonic acid and aflatrem, have been assigned to a particular gene cluster. We used RNA-seq to compare expression of secondary metabolite genes in gene clusters for the closely related fungi A. parasiticus, A. oryzae, and A. flavus S and L sclerotial morphotypes. The data help to refine the identification of probable functional gene clusters within these species. Our results suggest that A. flavus, a prevalent contaminant of maize, cottonseed, peanuts and tree nuts, is capable of producing metabolites which, besides aflatoxin, could be an underappreciated contributor to its toxicity. Full article

Review

Jump to: Research

Open AccessReview Type I Interferons as Regulators of Human Antigen Presenting Cell Functions
Toxins 2014, 6(6), 1696-1723; doi:10.3390/toxins6061696
Received: 24 March 2014 / Revised: 15 May 2014 / Accepted: 16 May 2014 / Published: 26 May 2014
Cited by 3 | PDF Full-text (888 KB) | HTML Full-text | XML Full-text
Abstract
Type I interferons (IFNs) are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN [...] Read more.
Type I interferons (IFNs) are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN action mostly relies on their ability to modulate host innate and adaptive immune responses. Work in recent years has begun to elucidate the mechanisms by which type I IFNs modify the immune response, and this is now recognized to be due to effects on multiple cell types, including monocytes, dendritic cells (DCs), NK cells, T and B lymphocytes. An ensemble of results from both animal models and in vitro studies emphasized the key role of type I IFNs in the development and function of DCs, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate to adaptive immunity. The identification of IFN signatures in DCs and their dysregulation under pathological conditions will therefore be pivotal to decipher the complexity of this DC-IFN interaction and to better exploit the therapeutic potential of these cells. Full article
(This article belongs to the collection Toxicity and Therapeutic Interventions in the Immune System)
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Open AccessReview Overall View of Chemical and Biochemical Weapons
Toxins 2014, 6(6), 1761-1784; doi:10.3390/toxins6061761
Received: 11 April 2014 / Revised: 15 May 2014 / Accepted: 26 May 2014 / Published: 4 June 2014
Cited by 5 | PDF Full-text (504 KB) | HTML Full-text | XML Full-text
Abstract
This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical [...] Read more.
This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist. Full article
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Open AccessReview Designing Vaccines to Neutralize Effective Toxin Delivery by Enterotoxigenic Escherichia coli
Toxins 2014, 6(6), 1799-1812; doi:10.3390/toxins6061799
Received: 7 March 2014 / Revised: 23 April 2014 / Accepted: 15 May 2014 / Published: 10 June 2014
Cited by 2 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
Enterotoxigenic Escherichia coli (ETEC) are a leading cause of diarrheal illness in developing countries. Despite the discovery of these pathogens as a cause of cholera-like diarrhea over 40 years ago, and decades of vaccine development effort, there remains no broadly protective ETEC [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) are a leading cause of diarrheal illness in developing countries. Despite the discovery of these pathogens as a cause of cholera-like diarrhea over 40 years ago, and decades of vaccine development effort, there remains no broadly protective ETEC vaccine. The discovery of new virulence proteins and an improved appreciation of the complexity of the molecular events required for effective toxin delivery may provide additional avenues to pursue in development of an effective vaccine to prevent severe diarrhea caused by these important pathogens. Full article
(This article belongs to the Special Issue Toxin-Antibody Interactions)
Open AccessReview Oligopeptides as Biomarkers of Cyanobacterial Subpopulations. Toward an Understanding of Their Biological Role
Toxins 2014, 6(6), 1929-1950; doi:10.3390/toxins6061929
Received: 23 April 2014 / Revised: 9 June 2014 / Accepted: 16 June 2014 / Published: 23 June 2014
Cited by 12 | PDF Full-text (552 KB) | HTML Full-text | XML Full-text
Abstract
Cyanobacterial oligopeptides comprise a wide range of bioactive and/or toxic compounds. While current research is strongly focused on exploring new oligopeptide variants and their bioactive properties, the biological role of these compounds remains elusive. Oligopeptides production abilities show a remarkably patchy distribution [...] Read more.
Cyanobacterial oligopeptides comprise a wide range of bioactive and/or toxic compounds. While current research is strongly focused on exploring new oligopeptide variants and their bioactive properties, the biological role of these compounds remains elusive. Oligopeptides production abilities show a remarkably patchy distribution among conspecific strains. This observation has prompted alternative approaches to unveil their adaptive value, based on the use of cellular oligopeptide compositions as biomarkers of intraspecific subpopulations or chemotypes in freshwater cyanobacteria. Studies addressing the diversity, distribution, and dynamics of chemotypes in natural systems have provided important insights into the structure and ecology of cyanobacterial populations and the adaptive value of oligopeptides. This review presents an overview of the fundamentals of this emerging approach and its most relevant findings, and discusses our current understanding of the role of oligopeptides in the ecology of cyanobacteria. Full article
(This article belongs to the Special Issue Genomics and Proteomics of Cyanotoxins)

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