A Novel Cyanobacterial Nostocyclopeptide is a Potent Antitoxin against Microcystins (original) (raw)
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The cyanotoxin-microcystins: current overview
Reviews in Environmental Science and Bio/Technology, 2014
The monocyclic heptapeptides microcystins (MCs), are a group of hepatotoxins, produced worldwide by some bloom-forming cyanobacterial species/strains both in marine and freshwater ecosystems. MCs are synthesized non-ribosomally by large multi-enzyme complexes consisting of different modules including polyketide synthases and non-ribosomal peptide synthetases, as well as several tailoring enzymes. More than 85 different variants of MCs have been reported to exist in nature. These are chemically stable, but undergo bio-degradation in natural water reservoirs. Direct or indirect intake of MCs through the food web is assumed to be a highly exposed route in risk assessment of cyanotoxins. MCs are the most commonly found cyanobacterial toxins that cause a major challenge for the production of safe drinking water and pose a serious threat to global public health as well as fundamental ecological processes due to their potential carcinogenicity. Here, we emphasize recent updates on different modes of action of their possible carcinogenicity. Besides the harmful effects on human and animals, MC producing cyanobacteria can also present a harmful effect on growth and development of agriculturally important plants. Overall, this review emphasizes the current understanding of MCs with their occurrence, geographical distribution, accumulation in the aquatic as well as terrestrial ecosystems, biosynthesis, climate-driven changes in their synthesis, stability and current aspects on its degradation, analysis, mode of action and their ecotoxicological effects.
Applied and Environmental Microbiology
A strain of the filamentous cyanobacterium Nostoc sp. isolated from a lake in Finland was found to produce at least nine hepatotoxic peptides with chemical and toxicological properties similar to those of the hepatotoxic heptaand pentapeptides produced by other cyanobacteria. Toxins were isolated and purified by highperformance liquid chromatography. Amounts available for five of the purified toxins (P6, P14, P15, P16, and P18) were adequate for high-performance liquid chromatography amino acid analysis and determination of molecular weight by fast-atom bombardment-mass spectrometry (FAB-MS). Quantities of three toxins (P14, P15, and P16) were adequate for further analysis by high-resolution FAB-MS, FAB-MS/MS, and 'H-nuclear magnetic resonance. Analysis showed that the toxins are new types of microcystin-LR homologs. Microcystin-LR contains equimolar amounts of D-alanine, L-leucine, D-erythro-4-methylaspartic acid, L-arginine, ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid), D-glutamic acid, and N-methyldehy-
Applied and …, 1990
A strain of the filamentous cyanobacterium Nostoc sp. isolated from a lake in Finland was found to produce at least nine hepatotoxic peptides with chemical and toxicological properties similar to those of the hepatotoxic heptaand pentapeptides produced by other cyanobacteria. Toxins were isolated and purified by highperformance liquid chromatography. Amounts available for five of the purified toxins (P6, P14, P15, P16, and P18) were adequate for high-performance liquid chromatography amino acid analysis and determination of molecular weight by fast-atom bombardment-mass spectrometry (FAB-MS). Quantities of three toxins (P14, P15, and P16) were adequate for further analysis by high-resolution FAB-MS, FAB-MS/MS, and 'H-nuclear magnetic resonance. Analysis showed that the toxins are new types of microcystin-LR homologs. Microcystin-LR contains equimolar amounts of D-alanine, L-leucine, D-erythro-4-methylaspartic acid, L-arginine, ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid), D-glutamic acid, and N-methyldehydroalanine (molecular weight [MW], 994). Nostoc sp. strain 152 was found to produce the following microcystin-LR homologs: (i) P6 contains an extra methylene group most probably due to the presence of N-methyldehydrobutyrine instead of N-methyldehydroalanine (MW, 1,008); (ii) P14 is O-acetyl-O-demethyl ADDA-microcystin-LR (MW, 1,022); (iii) P15 is 3-demethyl-O-acetylADDA-homoarginine-microcystin-LR (MW, 1,036); (iv) P16 is 3-demethyl-O-acetyl-O-demethylADDA-microcystin-LR (MW, 1,008); (v) P18 is 3demethyl-O-acetyl-O-demethylADDA-homoarginine-microcystin-LR (MW, 1,022). The toxicities of the new microcystin homologs were not significantly different from those of microcystin-LR or demethylmicrocystin-LR.
FEMS Microbiology Letters, 2000
Immunoassays are increasingly used to investigate the production, properties and fates of the cyanobacterial hepatotoxic microcystins in vitro and in vivo. Responses of an ELISA immunoassay to microcystins have been determined using the authentic toxin antigen, microcystin-LR, and conjugation products between the toxin and glutathione, cysteine-glycine and cysteine. The antibodies against microcystin-LR crossreacted with the toxin conjugation products with similar affinities (96^112%) to that of microcystin-LR, when assayed at a concentration of 1 Wg l 31 . Toxicity assessment of the conjugates, in comparison to microcystin-LR, indicated a reduction according to mouse bioassay. In vitro protein phosphatase inhibition assay indicated that the conjugates possessed approximately 3^9-fold lower toxicity than microcystin-LR. ß : S 0 3 7 8 -1 0 9 7 ( 0 0 ) 0 0 2 7 0 -6
Methods for determining microcystins (peptide hepatotoxins) and microcystin-producing cyanobacteria
Water Research, 2006
Episodes of cyanobacterial toxic blooms and fatalities to animals and humans due to cyanobacterial toxins (CBT) are known worldwide. The hepatotoxins and neurotoxins (cyanotoxins) produced by bloom-forming cyanobacteria have been the cause of human and animal health hazards and even death. Prevailing concentration of cell bound endotoxin, exotoxin and the toxin variants depend on developmental stages of the bloom and the cyanobacterial (CB) species involved. Toxic and non-toxic strains do not show any predictable morphological difference. The current instrumental, immunological and molecular methods applied for determining microcystins (peptide hepatotoxins) and microcystin-producing cyanobacteria are reviewed.
Environmental Toxicology, 2018
Cylindrospermopsin (CYN) and Microcystin-LR (MC-LR) are toxins produced by different cyanobacterial species, which are found mainly in freshwater reservoirs. Both of them can induce, separately, toxic effects in humans and wildlife. However, little is known about the toxic effects of the combined exposure, which could likely happen, taking into account the concomitant occurrence of the producers. As both cyanotoxins are well known to induce hepatic damage, the human hepatocellular HepG2 cell line was selected for the present study. Thus, the cytotoxicity of both pure cyanotoxins alone (0-5 μg/mL CYN and 0-120 μg/mL MC-LR) and in combination for 24 and 48 h was assayed, as long as the cytotoxicity of extracts from CYN-producing and nonproducing cyanobacterial species. The potential interaction of the combination was evaluated by the isobologram or Chou-Talalay's method, which provides a combination index as a quantitative measure of the two cyanotoxins interaction's degree. Moreover, a morphological study of the individual pure toxins and their combinations was also performed. Results showed that CYN was the most toxic pure cyanotoxin, being the mean effective concentrations obtained ≈4 and 90 μg/mL for CYN and MC-LR, respectively after 24 h. However, the simultaneous exposure showed an antagonistic effect. Morphologically, autophagy, at low concentrations, and apoptosis, at high concentrations were observed, with affectation of the rough endoplasmic reticulum and mitochondria. These effects were more pronounced with the combination. Therefore, it is important to assess the toxicological profile of cyanotoxins combinations in order to perform more realistic risk evaluations.