nodularin and anatoxin-a

Cyanobacteria are capable of thriving in almost all environments. Recent changes in climatic conditions due to increased human activities favor the occurrence and severity of harmful cyanobacterial bloom all over the world. Knowledge of the regulation of cyanotoxins by the various environmental factors is essential for effective management of toxic cyanobacterial bloom. In recent years, progress in the field of molecular mechanisms involved in cyanotoxin production has paved the way for assessing the role of various factors on the cyanotoxin production. In this review, we present an overview of the influence of various environmental factors on the production of major group of cyanotoxins, including microcystins, nodularin, cylindrospermopsin, anatoxins and saxitoxins.

Topics: Alkaloids; Animals; Bacterial Toxins; Climate Change; Cyanobacteria; Cyanobacteria Toxins; Environment; Humans; Marine Toxins; Microcystins; Peptides, Cyclic; Saxitoxin; Tropanes; Uracil

The treatment of cyanobacterial metabolites can consume many resources for water authorities which can be problematic especially with the recent shift away from chemical- and energy-intensive processes towards carbon and climate neutrality. In recent times, there has been a renaissance in biological treatment, in particular, biological filtration processes, for cyanobacteria metabolite removal. This in part, is due to the advances in molecular microbiology which has assisted in further understanding the biodegradation processes of specific cyanobacteria metabolites. However, there is currently no concise portfolio which captures all the pertinent information for the biological treatment of a range of cyanobacterial metabolites. This review encapsulates all the relevant information to date in one document and provides insights into how biological treatment options can be implemented in treatment plants for optimum cyanobacterial metabolite removal.

Topics: Alkaloids; Animals; Bacterial Toxins; Biodegradation, Environmental; Camphanes; Cyanobacteria; Cyanobacteria Toxins; Filtration; Humans; Microcystins; Naphthols; Peptides, Cyclic; Saxitoxin; Tropanes; Uracil; Water Purification

Topics: Alkaloids; Amino Acids, Diamino; Animals; Bacterial Toxins; Cyanobacteria; Cyanobacteria Toxins; Eutrophication; Humans; Marine Toxins; Microcystins; Peptides, Cyclic; Pharmacokinetics; Public Health; Saxitoxin; Tropanes; Uracil

Topics: Alkaloids; Animals; Bacterial Proteins; Bacterial Toxins; Biological Evolution; Cyanobacteria; Cyanobacteria Toxins; Eutrophication; Fresh Water; Gene Expression; Genes, Bacterial; Genomics; Humans; Marine Toxins; Microcystins; Peptide Synthases; Peptides, Cyclic; Saxitoxin; Tropanes; Uracil

Poisoning of livestock by toxic cyanobacteria was first reported in the 19th century, and throughout the 20th century cyanobacteria-related poisonings of livestock and wildlife in all continents have been described. Some mass mortality events involving unrelated fauna in prehistoric times have also been attributed to cyanotoxin poisoning; if correct, this serves as a reminder that toxic cyanobacteria blooms predate anthropogenic manipulation of the environment, though there is probably general agreement that human intervention has led to increases in the frequency and extent of cyanobacteria blooms. Many of the early reports of cyanobacteria poisoning were anecdotal and circumstantial, albeit with good descriptions of the appearance and behaviour of cyanobacteria blooms that preceded or coincided with illness and death in exposed animals. Early necropsy findings of hepatotoxicity were subsequently confirmed by experimental investigations. More recent reports supplement clinical and post-mortem findings with investigative chemistry techniques to identify cyanotoxins in stomach contents and tissue fluids.

Topics: Alkaloids; Animals; Animals, Domestic; Animals, Wild; Bacterial Toxins; Birds; Cyanobacteria; Cyanobacteria Toxins; Eutrophication; History, 20th Century; History, 21st Century; History, Ancient; Marine Toxins; Microcystins; Peptides, Cyclic; Saxitoxin; Tropanes; Uracil

Blue-green algae are found in lakes, ponds, rivers and brackish waters throughout the world. In case of excessive growth such as bloom formation, these bacteria can produce inherent toxins in quantities causing toxicity in mammals, including humans. These cyanotoxins include cyclic peptides and alkaloids. Among the cyclic peptides are the microcystins and the nodularins. The alkaloids include anatoxin-a, anatoxin-a(S), cylindrospermopsin, saxitoxins (STXs), aplysiatoxins and lyngbyatoxin. Both biological and chemical methods are used to determine cyanotoxins. Bioassays and biochemical assays are nonspecific, so they can only be used as screening methods. HPLC has some good prospects. For the subsequent detection of these toxins different detectors may be used, ranging from simple UV-spectrometry via fluorescence detection to various types of MS. The main problem in the determination of cyanobacterial toxins is the lack of reference materials of all relevant toxins. In general, toxicity data on cyanotoxins are rather scarce. A majority of toxicity data are known to be of microcystin-LR. For nodularins, data from a few animal studies are available. For the alkaloids, limited toxicity data exist for anatoxin-a, cylindrospermopsin and STX. Risk assessment for acute exposure could be relevant for some types of exposure. Nevertheless, no acute reference doses have formally been derived thus far. For STX(s), many countries have established tolerance levels in bivalves, but these limits were set in view of STX(s) as biotoxins, accumulating in marine shellfish. Official regulations for other cyanotoxins have not been established, although some (provisional) guideline values have been derived for microcystins in drinking water by WHO and several countries.

Topics: Alkaloids; Bacterial Toxins; Biodegradation, Environmental; Cyanobacteria; Cyanobacteria Toxins; Lyngbya Toxins; Marine Toxins; Microcystins; Peptides, Cyclic; Saxitoxin; Tropanes; Uracil

Mass developments of cyanobacteria ("blue-green algae") in lakes and brackish waters have repeatedly led to serious concerns due to their frequent association with toxins. Among these are the widespread hepatotoxins microcystin (MC) and nodularin (NOD). Here, we give an overview about the ecostrategies of the diverse toxin-producing species and about the genes and enzymes that are involved in the biosynthesis of the cyclic peptides. We further summarize current knowledge about toxicological mechanisms of MC and NOD, including protein phosphatase inhibition, oxidative stress and their tumor-promoting capabilities. One biotransformation pathway for MC is described. Mechanisms of cyanobacterial neurotoxins (anatoxin-a, homanatoxin-a, and anatoxin-a(s)) are briefly explained. We highlight selected cases of human fatalities related to the toxins. A special focus is given to evident cases of contamination of food supplements with cyanobacterial toxins, and to the necessary precautions.

Topics: Animals; Bacterial Toxins; Carcinogens; Chemical and Drug Induced Liver Injury; Cyanobacteria; Cyanobacteria Toxins; Dietary Supplements; Ecosystem; Food Contamination; Humans; Marine Toxins; Microcystins; Oxidative Stress; Peptides, Cyclic; Phosphoprotein Phosphatases; Tropanes

Topics: Alkaloids; Bacterial Toxins; Chromatography, High Pressure Liquid; Cyanobacteria; Cyanobacteria Toxins; Drinking Water; Limit of Detection; Marine Toxins; Mass Spectrometry; Microcystins; Peptides, Cyclic; Reproducibility of Results; Tropanes; Water Microbiology; Water Supply

Topics: Bacterial Toxins; Chromatography, High Pressure Liquid; Cyanobacteria Toxins; Drinking Water; Fresh Water; Limit of Detection; Marine Toxins; Mass Spectrometry; Microcystins; Mycotoxins; Peptides, Cyclic; Solid Phase Extraction; Spain; Tropanes; Water Pollutants, Chemical

Cyanobacteria can form dense blooms under specific environmental conditions, and some species produce secondary metabolites known as cyanotoxins, which present significant risks to public health and the environment. Identifying toxins produced by cyanobacteria present in surface water and fish is critical to ensuring high quality food and water for consumption, and protectionn of recreational uses. Current analytical screening methods typically focus on one class of cyanotoxins in a single matrix and rarely include saxitoxin. Thus, a cross-class screening method for microcystins, nodularin, anatoxin-a, cylindrospermopsin, and saxitoxin was developed to examine target analytes in environmental water and fish tissue. This was done, due to the broad range of cyanotoxin physicochemical properties, by pairing two extraction and separation techniques to improve isolation and detection. For the first time a zwitterionic hydrophilic interaction liquid chromatography column was evaluated to separate anatoxin-a, cylindrospermopsin, and saxitoxin, demonstrating greater sensitivity for all three compounds over previous techniques. Further, the method for microcystins, nodularin, anatoxin-a, and cylindrospermopsin were validated using isotopically labeled internal standards, again for the first time, resulting in improved compensation for recovery bias and matrix suppression. Optimized extractions for water and fish tissue can be extended to other congeners in the future. These improved separation and isotope dilution techniques are a launching point for more complex, non-targeted analyses, with preliminary targeted screening.

Topics: Alkaloids; Animals; Bacterial Toxins; Chromatography, Liquid; Cyanobacteria; Cyanobacteria Toxins; Environmental Monitoring; Fishes; Isotopes; Marine Toxins; Microcystins; Peptides, Cyclic; Saxitoxin; Tandem Mass Spectrometry; Tropanes; Uracil; Water

Developing easy-to-use and miniaturized detectors is essential for in-field monitoring of environmentally hazardous substances, such as the cyanotoxins. We demonstrated a differential fluorescent sensor array made of aptamers and single-stranded DNA (ssDNA) dyes for multiplexed detection and discrimination of four common cyanotoxins with an ordinary smartphone within 5 min of reaction. The assay reagents were preloaded and dried in a microfluidic chip with a long shelf life over 60 days. Upon the addition of analyte solutions, competitive binding of cyanotoxin to the specific aptamer-dye conjugate occurred. A zone-specific and concentration-dependent reduction in the green fluorescence was observed as a result of the aptamer conformation change. The aptasensors are fully optimized by quantification of their dissociation constants, tuning the stoichiometric ratios of reaction mixtures, and implementation of an internal intensity correction step. The fluorescent sensor array allowed for accurate identification and measurement of four important cyanotoxins, including anatoxin-a (ATX), cylindrospermopsin (CYN), nodularin (NOD), and microcystin-LR (MC-LR), in parallel, with the limit of detection (LOD) down to a few nanomolar (<3 nM), which is close to the World Health Organization's guideline for the maximum concentration allowed in drinking water. The smartphone-based sensor platform also showed remarkable chemical specificity against potential interfering agents in water. The performance of the system was tested and validated with real lake water samples that were contaminated with trace levels of individual cyanotoxins as well as binary, ternary, and quaternary mixtures. Finally, a smartphone app interface has been developed for rapid on-site data processing and result display.

Topics: Alkaloids; Aptamers, Nucleotide; Bacterial Toxins; Biosensing Techniques; Cyanobacteria Toxins; DNA, Single-Stranded; Fluorescence; Fresh Water; Humans; Lab-On-A-Chip Devices; Lakes; Limit of Detection; Marine Toxins; Microarray Analysis; Microcystins; Peptides, Cyclic; Smartphone; Tropanes; Uracil; Water Pollutants, Chemical

In 2016, the Pennsylvania Department of Environmental Protection conducted a limited survey of streams in the Susquehanna River basin in Pennsylvania, USA, to screen for microcystins/nodularins, anatoxin-a (ATX) and homoanatoxin-a (HTX). Testing revealed the presence of HTX in samples collected from the Pine Creek basin, with ATX present at lower levels. Microcystins/nodularins (MCs/NODs) were also tested and found to be concomitant, with NOD-R confirmed present by LC-MS/MS.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Cyanobacteria Toxins; Microcystins; Pennsylvania; Peptides, Cyclic; Periphyton; Rivers; Toxins, Biological; Tropanes

Monitoring the quality of freshwater is an important issue for public health. In the context of the European project μAqua, 150 samples were collected from several waters in France, Germany, Ireland, Italy, and Turkey for 2 yr. These samples were analyzed using 2 multitoxin detection methods previously developed: a microsphere-based method coupled to flow-cytometry, and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The presence of microcystins, nodularin, domoic acid, cylindrospermopsin, and several analogues of anatoxin-a (ATX-a) was monitored. No traces of cylindrospermopsin or domoic acid were found in any of the environmental samples. Microcystin-LR and microcystin-RR were detected in 2 samples from Turkey and Germany. In the case of ATX-a derivatives, 75% of samples contained mainly H

Topics: Alkaloids; Bacterial Toxins; Bridged Bicyclo Compounds, Heterocyclic; Chromatography, Liquid; Cyanobacteria; Cyanobacteria Toxins; Environmental Monitoring; Eutrophication; Flow Cytometry; France; Fresh Water; Germany; Italy; Limit of Detection; Marine Toxins; Microcystins; Molecular Structure; Peptides, Cyclic; Tandem Mass Spectrometry; Tropanes; Turkey; Uracil; Water Pollutants, Chemical

A fast and sensitive LC-MS method was developed for the simultaneous analysis of 11 cyanotoxins in drinking water. The toxins in this method included eight microcystins, as well as nodularin, anatoxin-a, and cylindrospermopsin. Sample processing involved a small sample volume and a direct dilution procedure that could be performed in minutes rather than hours using traditional SPE procedures. This method also featured a short acquisition time of 12 min with an adequate separation of all analytes. Validation results demonstrated good sensitivity with LODs <100 ng/L and good precision (RSD < 20%) and accuracy. Analyte stability was also thoroughly studied. The matrix effect was minimal, and tap water used for calibrators and controls. No sample carryover was observed after the highest concentration calibrator.

Topics: Alkaloids; Bacterial Toxins; Chromatography, Liquid; Cyanobacteria Toxins; Drinking Water; Microcystins; Peptides, Cyclic; Tandem Mass Spectrometry; Tropanes; Uracil; Water Pollutants, Chemical

A solid-phase extraction (SPE)-liquid chromatography (LC)-mass spectrometry (MS) method was developed to concentrate and detect nine cyanotoxins simultaneously, including six microcystins (MCs) congeners, nodularin (NOD), anatoxin-a (ATX) and cylindrospermopsin (CYN), in pure and natural waters. A dual cartridge SPE assembly was tested for the operating parameters of cyanotoxin extraction. A surrogate standard (SS), 1,9-diaminononane, was spiked in all the samples before the SPE extraction, and an internal standard (IS), 2,3,5-trimethylphenyl methyl carbamate, was spiked before LC/MS analysis. The method detection limit (MDL) was 2-100 ng/L for nine cyanotoxins in pure water and was increased by a factor of three to ten in a more complicated water matrix. The recoveries based on SS were between 83 and 104%, while those based on IS were 80-120%. The developed method was successfully employed in analyzing 33 water samples collected from eutrophic lakes, water treatment plants and distribution taps. MCs, NOD, and CYN were detected in the reservoir water, with concentrations as high as 36 μg/L. In addition, for the first time in Taiwan's tap water, CYN was detected at concentrations as high as 8.6 μg/L. Quality control data for the field samples shows that the analytical scheme developed is appropriate for monitoring cyanotoxins.

Topics: Alkaloids; Bacterial Proteins; Bacterial Toxins; Calibration; Chromatography, High Pressure Liquid; Cyanobacteria; Cyanobacteria Toxins; Drinking Water; Lakes; Limit of Detection; Microcystins; Peptides, Cyclic; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Taiwan; Tropanes; Uracil; Water Supply

Topics: Alkaloids; Animals; Bacterial Toxins; Cyanobacteria; Cyanobacteria Toxins; Dietary Supplements; Environmental Monitoring; Eutrophication; Fishes; Fresh Water; Geologic Sediments; Humans; Marine Toxins; Microcystins; Peptides, Cyclic; Plants; Shellfish; Tropanes; Uracil

Simple and easy-to-use bioassays with Artemia salina (brine shrimp) larvae, luminescent bacteria and Pseudomonas putida were evaluated for the detection of toxicity due to cyanobacterial hepato- and neurotoxins. The hepatotoxins and a neurotoxin, anatoxin-a, were extracted from laboratory-grown cultures and natural bloom samples by the solid phase fractionation method and dissolved in diluent for different bioassays. The toxin concentration of cyanobacterial extracts was determined with HPLC. The Artemia biotest appeared to be quite sensitive to cyanobacterial hepatotoxins, with LC 50 values of 3-17 mg l-1. The Artemia test was also shown to be of value for the detection of toxicity caused by anatoxin-a. The fractionated extract of anatoxin-a was not lethal to Artemia but it disturbed the ability of the larvae to move forwards. Filtered cyanobacterial cultures with anatoxin-a, on the other hand, caused mortality of Artemia larvae at concentrations of 2-14 mg l-1. With the solid phase fractionation of cyanobacterial samples, no non-specific toxicity due to compounds other than hepato- and neurotoxins was observed. In the luminescent bacteria test, the inhibition of luminescence did not correlate with the abundance of hepatotoxins or anatoxin-a. The growth of Ps. putida was enhanced, rather than inhibited by cyanobacterial toxin fractions.

Topics: Animals; Artemia; Bacterial Toxins; Cyanobacteria; Cyanobacteria Toxins; Marine Toxins; Microcystins; Peptides, Cyclic; Photobacterium; Pseudomonas putida; Tropanes; Vibrio