Research

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16 pages, 2985 KiB

Open AccessArticle

Mutations at Two Key Sites in PP2A Safeguard Caenorhabditis elegans Neurons from Microcystin-LR Toxicity

by Chunhua Zhan and Jianke Gong

Toxins 2024, 16(3), 145; https://doi.org/10.3390/toxins16030145 - 13 Mar 2024

Viewed by 825

Microcystin-LR (MC-LR) is a secondary metabolite produced by cyanobacteria, globally renowned for its potent hepatotoxicity. However, an increasing body of research suggests that it also exhibits pronounced neurotoxicity. PP2A is a fundamental intracellular phosphatase that plays a pivotal role in cell development and [...] Read more.

Microcystin-LR (MC-LR) is a secondary metabolite produced by cyanobacteria, globally renowned for its potent hepatotoxicity. However, an increasing body of research suggests that it also exhibits pronounced neurotoxicity. PP2A is a fundamental intracellular phosphatase that plays a pivotal role in cell development and survival. Although extensive research has focused on the binding of MC-LR to the C subunit of PP2A, few studies have explored the key amino acid sites that can prevent the binding of MC-LR to PP2A-C. Due to the advantages of Caenorhabditis elegans (C. elegans), such as ease of genetic editing and a short lifespan, we exposed nematodes to MC-LR in a manner that simulated natural exposure conditions based on MC-LR concentrations in natural water bodies (immersion exposure). Our findings demonstrate that MC-LR exerts comprehensive toxicity on nematodes, including reducing lifespan, impairing reproductive capabilities, and diminishing sensory functions. Notably, and for the first time, we observed that MC-LR neurotoxic effects can persist up to the F3 generation, highlighting the significant threat that MC-LR poses to biological populations in natural environments. Furthermore, we identified two amino acid sites (L252 and C278) in PP2A-C through mutations that prevented MC-LR binding without affecting PP2A activity. This discovery was robustly validated through behavioral studies and neuronal calcium imaging using nematodes. In conclusion, we identified two crucial amino acid sites that could prevent MC-LR from binding to PP2A-C, which holds great significance for the future development of MC-LR detoxification drugs. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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17 pages, 7090 KiB

Open AccessArticle

Gut Microbiota of Freshwater Gastropod (Bellamya aeruginosa) Assist the Adaptation of Host to Toxic Cyanobacterial Stress

by Hongfang Liu, Xianming Yang, Wen Yang, Zhongming Zheng and Jinyong Zhu

Toxins 2023, 15(4), 252; https://doi.org/10.3390/toxins15040252 - 29 Mar 2023

Cited by 3 | Viewed by 1711

Abstract

Gut microbes play a critical role in helping hosts adapt to external environmental changes and are becoming an important phenotype for evaluating the response of aquatic animals to environmental stresses. However, few studies have reported the role that gut microbes play after the [...] Read more.

Gut microbes play a critical role in helping hosts adapt to external environmental changes and are becoming an important phenotype for evaluating the response of aquatic animals to environmental stresses. However, few studies have reported the role that gut microbes play after the exposure of gastropods to bloom-forming cyanobacteria and toxins. In this study, we investigated the response pattern and potential role of intestinal flora in freshwater gastropod Bellamya aeruginosa when exposed to toxic and non-toxic strains of Microcystis aeruginosa, respectively. Results showed that the composition of the intestinal flora of the toxin-producing cyanobacteria group (T group) changed significantly over time. The concentration of microcystins (MCs) in hepatopancreas tissue decreased from 2.41 ± 0.12 on day 7 to 1.43 ± 0.10 μg·g⁻¹ dry weight on day 14 in the T group. The abundance of cellulase-producing bacteria (Acinetobacter) was significantly higher in the non-toxic cyanobacteria group (NT group) than that in the T group on day 14, whereas the relative abundance of MC-degrading bacteria (Pseudomonas and Ralstonia) was significantly higher in the T group than that in the NT group on day 14. In addition, the co-occurrence networks in the T group were more complex than that in the NT group at day 7 and day 14. Some genera identified as key nodes, such as Acinetobacter, Pseudomonas, and Ralstonia, showed different patterns of variation in the co-occurrence network. Network nodes clustered to Acinetobacter increased in the NT group from day 7 to day 14, whereas the interactions between Pseudomonas and Ralstonia and other bacteria almost changed from positive correlations in the D7T group to negative correlations in the D14T group. These results suggested that these bacteria not only have the ability to improve host resistance to toxic cyanobacterial stress by themselves, but they can also further assist host adaptation to environmental stress by regulating the interaction patterns within the community. This study provides useful information for understanding the role of freshwater gastropod gut flora in response to toxic cyanobacteria and reveals the underlying tolerance mechanisms of B. aeruginosa to toxic cyanobacteria. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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19 pages, 3065 KiB

Open AccessArticle

Integration of Transcriptomics and Microbiomics Reveals the Responses of Bellamya aeruginosa to Toxic Cyanobacteria

by Xianming Yang, Jinyong Zhu, Chaoyang Hu, Wen Yang and Zhongming Zheng

Toxins 2023, 15(2), 119; https://doi.org/10.3390/toxins15020119 - 01 Feb 2023

Cited by 2 | Viewed by 1497

Abstract

Frequent outbreaks of harmful cyanobacterial blooms and the cyanotoxins they produce not only seriously jeopardize the health of freshwater ecosystems but also directly affect the survival of aquatic organisms. In this study, the dynamic characteristics and response patterns of transcriptomes and gut microbiomes [...] Read more.

Frequent outbreaks of harmful cyanobacterial blooms and the cyanotoxins they produce not only seriously jeopardize the health of freshwater ecosystems but also directly affect the survival of aquatic organisms. In this study, the dynamic characteristics and response patterns of transcriptomes and gut microbiomes in gastropod Bellamya aeruginosa were investigated to explore the underlying response mechanisms to toxic cyanobacterial exposure. The results showed that toxic cyanobacteria exposure induced overall hepatopancreatic transcriptome changes. A total of 2128 differentially expressed genes were identified at different exposure stages, which were mainly related to antioxidation, immunity, and metabolism of energy substances. In the early phase (the first 7 days of exposure), the immune system may notably be the primary means of resistance to toxin stress, and it performs apoptosis to kill damaged cells. In the later phase (the last 7 days of exposure), oxidative stress and the degradation activities of exogenous substances play a dominant role, and nutrient substance metabolism provides energy to the body throughout the process. Microbiomic analysis showed that toxic cyanobacteria increased the diversity of gut microbiota, enhanced interactions between gut microbiota, and altered microbiota function. In addition, the changes in gut microbiota were correlated with the expression levels of antioxidant-, immune-, metabolic-related differentially expressed genes. These results provide a comprehensive understanding of gastropods and intestinal microbiota response to toxic cyanobacterial stress. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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25 pages, 6207 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Subchronic Oral Cylindrospermopsin Exposure Alters the Host Gut Microbiome and Is Associated with Progressive Hepatic Inflammation, Stellate Cell Activation, and Mild Fibrosis in a Preclinical Study

by Punnag Saha, Macayla Upright, Dipro Bose, Subhajit Roy, Ayushi Trivedi, Madhura More, Geoff I. Scott, Bryan W. Brooks and Saurabh Chatterjee

Toxins 2022, 14(12), 835; https://doi.org/10.3390/toxins14120835 - 01 Dec 2022

Cited by 4 | Viewed by 3031

Abstract

Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among [...] Read more.

Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among the emerging threats from cyanotoxins, new evidence shows cylindrospermopsin release in freshwater lakes. A known hepatotoxin in higher concentrations, we examined the possible role of cylindrospermopsin in causing host gut dysbiosis and its association with liver pathology in a mouse model of toxico-pharmacokinetics and hepatic pathology. The results showed that oral exposure to cylindrospermopsin caused decreased diversity of gut bacteria phyla accompanied by an increased abundance of Clostridioides difficile and decreased abundance of probiotic flora such as Roseburia, Akkermanssia, and Bacteroides thetaiotamicron, a signature most often associated with intestinal and hepatic pathology and underlying gastrointestinal disease. The altered gut dysbiosis was also associated with increased Claudin2 protein in the intestinal lumen, a marker of gut leaching and endotoxemia. The study of liver pathology showed marked liver inflammation, the release of damage-associated molecular patterns, and activation of toll-like receptors, a hallmark of consistent and progressive liver damage. Hepatic pathology was also linked to increased Kupffer cell activation and stellate cell activation, markers of progressive liver damage often linked to the development of liver fibrosis and carcinoma. In conclusion, the present study provides additional evidence of cylindrospermopsin-linked progressive liver pathology that may be very well-linked to gut dysbiosis, though definitive evidence involving this link needs to be studied further. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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17 pages, 2568 KiB

Open AccessArticle

Transcriptome Analysis Reveals the Algicidal Mechanism of Brevibacillus laterosporus against Microcystis aeruginosa through Multiple Metabolic Pathways

by Yulei Zhang, Jieyi Li, Zhangxi Hu, Dong Chen, Feng Li, Xianghu Huang and Changling Li

Toxins 2022, 14(7), 492; https://doi.org/10.3390/toxins14070492 - 15 Jul 2022

Cited by 6 | Viewed by 2188

Abstract

It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality and ecological environment and causes huge economic losses. Algicidal bacteria have a promising application prospect in controlling cyanobacterial [...] Read more.

It is widely accepted that eutrophication has played an important role in the formation of harmful cyanobacterial blooms in recent decades, which impacts water quality and ecological environment and causes huge economic losses. Algicidal bacteria have a promising application prospect in controlling cyanobacterial blooms in aquaculture water. Here, the process of the algicidal bacterium Brevibacillus laterosporus strain Bl-zj acting on Microcystis aeruginosa was explored using transcriptome analysis to elucidate the algicidal mechanism. The results of the co-culture of bacterium and alga showed a strong alga-lysing effect of B. laterosporus against M. aeruginosa with an extreme morphology deformation of the algal cells. A total of 2744 differentially expressed genes of B. laterosporus were identified, which were mainly involved in the metabolism of amino acid, carbohydrate, and lipid. In the co-cultured group, the expression of genes mainly enriched in valine, leucine and isoleucine degradation, and fatty acid degradation were significantly increased. However, the expression of the genes related to ribosome were mainly inhibited. Transcriptome analysis showed that B. laterosporus obtained ATP and energy by the degradation of valine, leucine, isoleucine, and fatty acids, and destroyed algal cells by efflux pump transporters, secretion of hydrolytic enzymes, antibiotics, proteases, and other secondary metabolites, resulting in algal death and achieving the algicidal effect. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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17 pages, 3173 KiB

Open AccessArticle

Gill Junction Injury and Microbial Disorders Induced by Microcystin-Leucine Arginine in Lithobates catesbeianus Tadpoles

by Huiling Jiang, Jun He, Hui Wang, Lingling Zheng, Xiaoran Wang, Huijuan Zhang, Hailong Wu and Yilin Shu

Toxins 2022, 14(7), 479; https://doi.org/10.3390/toxins14070479 - 13 Jul 2022

Cited by 3 | Viewed by 1823

Abstract

Microcystin-LR (MC-LR) is widely present in waters around the world, but its potential toxic effects and mechanisms on amphibian gills remain unknown. In the present study, tadpoles (Lithobates catesbeianus) were exposed to environmentally realistic concentrations of 0.5, 2 μg/L MC-LR, and [...] Read more.

Microcystin-LR (MC-LR) is widely present in waters around the world, but its potential toxic effects and mechanisms on amphibian gills remain unknown. In the present study, tadpoles (Lithobates catesbeianus) were exposed to environmentally realistic concentrations of 0.5, 2 μg/L MC-LR, and 0 μg/L MC-LR (Control) for 30 days with the objective to unveil the impairment of gill health. The lysozyme was downregulated, while pattern recognition receptors and complement and adaptive immune processes were upregulated and the ability of gill supernatant to inhibit pathogenic bacteria decreased in the 0.5 and 2 μg/L MC-LR groups. The transcriptions of epithelial barrier components (e.g., CLDN1) were significantly decreased in MC-LR-exposed gills, while the gill content of lipopolysaccharide (LPS) endotoxins and the transcriptions of downstream responsive genes (e.g., TLR4 and NF-κB) were concurrently increased. In addition, the number of eosinophils and the expression of pro-inflammatory cytokines (e.g., IL-1β and TNF-α) were increased. These results imply that exposure of tadpoles to low environmentally concentrations of MC-LR leads to inflammation, increased permeability, and a reduced ability to inhibit pathogenic bacteria. The epithelial cells of inner gill filaments increased and transcriptions of hypoxic stress genes (e.g., HIF-1α, FLT1, and SERPINE1) were upregulated within the exposed group. As a consequence, exposure to MC-LR may lead to hypoxic stress. MC-LR exposure also drove gill microbiota to a dysbiosis. The relative abundance of Elizabethkingia was positively correlated with content of LPS and transcriptions of NF-κB and TNF-α. Overall, this study presents the first evidence about the pronounced impacts of MC-LR exposure on gills of amphibians, highlighting the susceptibility of early developing tadpoles to the environmental risks of MC-LR. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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17 pages, 3599 KiB

Open AccessArticle

Genotoxicity of Natural Water during the Mass Development of Cyanobacteria Evaluated by the Allium Test Method: A Model Experiment with Microcosms

by Dmitry S. Pesnya, Svetlana A. Kurbatova, Andrey N. Sharov, Ekaterina N. Chernova, Igor Y. Yershov, Galina V. Shurganova and Ekaterina L. Vodeneeva

Toxins 2022, 14(5), 359; https://doi.org/10.3390/toxins14050359 - 21 May 2022

Cited by 3 | Viewed by 2589

Abstract

Cyanobacteria, which develop abundantly in aquatic ecosystems, can be harmful to humans and animals not only by releasing toxins that cause poisoning but also by provoking cytogenetic effects. The influence of the mass development of cyanobacteria on the genotoxic properties of natural water [...] Read more.

Cyanobacteria, which develop abundantly in aquatic ecosystems, can be harmful to humans and animals not only by releasing toxins that cause poisoning but also by provoking cytogenetic effects. The influence of the mass development of cyanobacteria on the genotoxic properties of natural water has been studied in model ecosystems (microcosms) with different compositions of biotic components (zooplankton, amphipods and fish). The validated plant test system “Allium test” was used in this study. Genotoxic effects were detected at microcystin concentrations below those established by the World Health Organization (WHO) for drinking water. In all experimental treatments, cells with disorders such as polyploidy and mitotic abnormalities associated with damage to the mitotic spindle, including c-mitosis, as well as lagging chromosomes were found. Genotoxic effects were associated with the abundance of cyanobacteria, which, in turn, depended on the composition of aquatic organisms in the experimental ecosystem. Fish, to a greater extent than other aquatic animals, maintain an abundance of cyanobacteria. After one month, in microcosms with fish, mitotic abnormalities and polyploidy continued to be detected, whereas in other treatments, there were no statistically significant genotoxic effects. In microcosms with amphipods, the number and biomass of cyanobacteria decreased to the greatest extent, and only one parameter of genotoxic activity (frequency of polyploidy) significantly differed from the control. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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14 pages, 1760 KiB

Open AccessArticle

Lipopolysaccharide from the Cyanobacterium Geitlerinema sp. Induces Neutrophil Infiltration and Lung Inflammation

by Julie A. Swartzendruber, Rosalinda Monroy Del Toro, Ryan Incrocci, Nessa Seangmany, Joshua R. Gurr, Alejandro M. S. Mayer, Philip G. Williams and Michelle Swanson-Mungerson

Toxins 2022, 14(4), 267; https://doi.org/10.3390/toxins14040267 - 09 Apr 2022

Cited by 6 | Viewed by 2637

Abstract

Glucocorticoid-resistant asthma, which predominates with neutrophils instead of eosinophils, is an increasing health concern. One potential source for the induction of neutrophil-predominant asthma is aerosolized lipopolysaccharide (LPS). Cyanobacteria have recently caused significant tidal blooms, and aerosolized cyanobacterial LPS has been detected near the [...] Read more.

Glucocorticoid-resistant asthma, which predominates with neutrophils instead of eosinophils, is an increasing health concern. One potential source for the induction of neutrophil-predominant asthma is aerosolized lipopolysaccharide (LPS). Cyanobacteria have recently caused significant tidal blooms, and aerosolized cyanobacterial LPS has been detected near the cyanobacterial overgrowth. We hypothesized that cyanobacterial LPS contributes to lung inflammation by increasing factors that promote lung inflammation and neutrophil recruitment. To test this hypothesis, c57Bl/6 mice were exposed intranasally to LPS from the cyanobacterium member, Geitlerinema sp., in vivo to assess neutrophil infiltration and the production of pro-inflammatory cytokines and chemokines from the bronchoalveolar fluid by ELISA. Additionally, we exposed the airway epithelial cell line, A549, to Geitlerinema sp. LPS in vitro to confirm that airway epithelial cells were stimulated by this LPS to increase cytokine production and the expression of the adhesion molecule, ICAM-1. Our data demonstrate that Geitlerinema sp. LPS induces lung neutrophil infiltration, the production of pro-inflammatory cytokines such as Interleukin (IL)-6, Tumor necrosis factor-alpha, and Interferongamma as well as the chemokines IL-8 and RANTES. Additionally, we demonstrate that Geitlerinema sp. LPS directly activates airway epithelial cells to produce pro-inflammatory cytokines and the adhesion molecule, Intercellular Adhesion Molecule-1 (ICAM-1), in vitro using the airway epithelial cell line, A549. Based on our findings that use Geitlerinema sp. LPS as a model system, the data indicate that cyanobacteria LPS may contribute to the development of glucocorticoid-resistant asthma seen near water sources that contain high levels of cyanobacteria. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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16 pages, 1134 KiB

Open AccessArticle

Assessment of Common Cyanotoxins in Cyanobacteria of Biological Loess Crusts

by Tamara Dulić, Zorica Svirčev, Tamara Palanački Malešević, Elisabeth J. Faassen, Henna Savela, Qingzhen Hao and Jussi Meriluoto

Toxins 2022, 14(3), 215; https://doi.org/10.3390/toxins14030215 - 16 Mar 2022

Cited by 5 | Viewed by 3125

Abstract

Cyanotoxins are a diverse group of bioactive compounds produced by cyanobacteria that have adverse effects on human and animal health. While the phenomenon of cyanotoxin production in aquatic environments is well studied, research on cyanotoxins in terrestrial environments, where cyanobacteria abundantly occur in [...] Read more.

Cyanotoxins are a diverse group of bioactive compounds produced by cyanobacteria that have adverse effects on human and animal health. While the phenomenon of cyanotoxin production in aquatic environments is well studied, research on cyanotoxins in terrestrial environments, where cyanobacteria abundantly occur in biocrusts, is still in its infancy. Here, we investigated the potential cyanotoxin production in cyanobacteria-dominated biological loess crusts (BLCs) from three different regions (China, Iran, and Serbia) and in cyanobacterial cultures isolated from the BLCs. The presence of cyanotoxins microcystins, cylindrospermopsin, saxitoxins, and β-N-methylamino-L-alanine was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, while the presence of cyanotoxin-encoding genes (mcyE, cyrJ, sxtA, sxtG, sxtS, and anaC) was investigated by polymerase chain reaction (PCR) method. We could not detect any of the targeted cyanotoxins in the biocrusts or the cyanobacterial cultures, nor could we amplify any cyanotoxin-encoding genes in the cyanobacterial strains. The results are discussed in terms of the biological role of cyanotoxins, the application of cyanobacteria in land restoration programs, and the use of cyanotoxins as biosignatures of cyanobacterial populations in loess research. The article highlights the need to extend the field of research on cyanobacteria and cyanotoxin production to terrestrial environments. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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13 pages, 12768 KiB

Open AccessArticle

Temporal Patterns of Bacterial and Viral Communities during Algae Blooms of a Reservoir in Macau

by Dini Hu, John P. Giesy, Min Guo, Wai Kin Ung, Yijun Kong, Kai Meng Mok and Simon Ming-Yuen Lee

Toxins 2021, 13(12), 894; https://doi.org/10.3390/toxins13120894 - 13 Dec 2021

Cited by 2 | Viewed by 2736

Abstract

Compositions of microbial communities associated with blooms of algae in a storage reservoir in Macau, China were investigated between 2013 and 2016. Algae were enumerated by visible light microscopy. Profiles of organisms in water were examined by 16S rRNA sequences and viral metagenomics, [...] Read more.

Compositions of microbial communities associated with blooms of algae in a storage reservoir in Macau, China were investigated between 2013 and 2016. Algae were enumerated by visible light microscopy. Profiles of organisms in water were examined by 16S rRNA sequences and viral metagenomics, based on next generation sequencing. Results of 16S rRNA sequencing indicated that majority of the identified organisms were bacteria closely related to Proteobacteria, Cyanobacteria, Verrucomicrobia, Bacteroidetes, and Actinobacteria. Metagenomics sequences demonstrated that the dominant virus was Phycodnavirus, accounting for 70% of the total population. Patterns of relative numbers of bacteria in the microbial community and their temporal changes were determined through alpha diversity indices, principal coordinates analysis (PCoA), relative abundance, and visualized by Venn diagrams. Ways in which the bacterial and viral communities are influenced by various water-related variables were elucidated based on redundancy analysis (RDA). Relationships of the relative numbers of bacteria with trophic status in a reservoir used for drinking water in Macau, provided insight into associations of Phycodnavirus and Proteobacteria with changes in blooms of algae. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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Review

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24 pages, 1599 KiB

Open AccessReview

Cyanobacterial Harmful Algal Bloom Toxin Microcystin and Increased Vibrio Occurrence as Climate-Change-Induced Biological Co-Stressors: Exposure and Disease Outcomes via Their Interaction with Gut–Liver–Brain Axis

by Saurabh Chatterjee and Madhura More

Toxins 2023, 15(4), 289; https://doi.org/10.3390/toxins15040289 - 17 Apr 2023

Cited by 7 | Viewed by 4196

Abstract

The effects of global warming are not limited to rising global temperatures and have set in motion a complex chain of events contributing to climate change. A consequence of global warming and the resultant climate change is the rise in cyanobacterial harmful algal [...] Read more.

The effects of global warming are not limited to rising global temperatures and have set in motion a complex chain of events contributing to climate change. A consequence of global warming and the resultant climate change is the rise in cyanobacterial harmful algal blooms (cyano-HABs) across the world, which pose a threat to public health, aquatic biodiversity, and the livelihood of communities that depend on these water systems, such as farmers and fishers. An increase in cyano-HABs and their intensity is associated with an increase in the leakage of cyanotoxins. Microcystins (MCs) are hepatotoxins produced by some cyanobacterial species, and their organ toxicology has been extensively studied. Recent mouse studies suggest that MCs can induce gut resistome changes. Opportunistic pathogens such as Vibrios are abundantly found in the same habitat as phytoplankton, such as cyanobacteria. Further, MCs can complicate human disorders such as heat stress, cardiovascular diseases, type II diabetes, and non-alcoholic fatty liver disease. Firstly, this review describes how climate change mediates the rise in cyanobacterial harmful algal blooms in freshwater, causing increased levels of MCs. In the later sections, we aim to untangle the ways in which MCs can impact various public health concerns, either solely or in combination with other factors resulting from climate change. In conclusion, this review helps researchers understand the multiple challenges brought forth by a changing climate and the complex relationships between microcystin, Vibrios, and various environmental factors and their effect on human health and disease. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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30 pages, 1972 KiB

Open AccessReview

Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases

by Galina Nugumanova, Eugene D. Ponomarev, Sholpan Askarova, Elizaveta Fasler-Kan and Natasha S. Barteneva

Toxins 2023, 15(3), 233; https://doi.org/10.3390/toxins15030233 - 21 Mar 2023

Cited by 6 | Viewed by 4603

Abstract

Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute [...] Read more.

Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. Major mechanisms related to the neurotoxicity of cyanobacteria compounds include (1) blocking of key proteins and channels; (2) inhibition of essential enzymes in mammalian cells such as protein phosphatases and phosphoprotein phosphatases as well as new molecular targets such as toll-like receptors 4 and 8. One of the widely discussed implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids. Recent research provides evidence that non-proteinogenic amino acid BMAA produced by cyanobacteria have multiple effects on translation process and bypasses the proof-reading ability of the aminoacyl-tRNA-synthetase. Aberrant proteins generated by non-canonical translation may be a factor in neuronal death and neurodegeneration. We hypothesize that the production of cyanopeptides and non-canonical amino acids is a more general mechanism, leading to mistranslation, affecting protein homeostasis, and targeting mitochondria in eukaryotic cells. It can be evolutionarily ancient and initially developed to control phytoplankton communities during algal blooms. Outcompeting gut symbiotic microorganisms may lead to dysbiosis, increased gut permeability, a shift in blood-brain-barrier functionality, and eventually, mitochondrial dysfunction in high-energy demanding neurons. A better understanding of the interaction between cyanopeptides metabolism and the nervous system will be crucial to target or to prevent neurodegenerative diseases. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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18 pages, 1469 KiB

Open AccessReview

Microcystin-Induced Immunotoxicity in Fishes: A Scoping Review

by Wang Lin, Tien-Chieh Hung, Tomofumi Kurobe, Yi Wang and Pinhong Yang

Toxins 2021, 13(11), 765; https://doi.org/10.3390/toxins13110765 - 29 Oct 2021

Cited by 18 | Viewed by 3640

Abstract

Cyanobacteria (blue-green algae) have been present on Earth for over 2 billion years, and can produce a variety of bioactive molecules, such as cyanotoxins. Microcystins (MCs), the most frequently detected cyanotoxins, pose a threat to the aquatic environment and to human health. The [...] Read more.

Cyanobacteria (blue-green algae) have been present on Earth for over 2 billion years, and can produce a variety of bioactive molecules, such as cyanotoxins. Microcystins (MCs), the most frequently detected cyanotoxins, pose a threat to the aquatic environment and to human health. The classic toxic mechanism of MCs is the inhibition of the protein phosphatases 1 and 2A (PP1 and PP2A). Immunity is known as one of the most important physiological functions in the neuroendocrine-immune network to prevent infections and maintain internal homoeostasis in fish. The present review aimed to summarize existing papers, elaborate on the MC-induced immunotoxicity in fish, and put forward some suggestions for future research. The immunomodulatory effects of MCs in fish depend on the exposure concentrations, doses, time, and routes of exposure. Previous field and laboratory studies provided strong evidence of the associations between MC-induced immunotoxicity and fish death. In our review, we summarized that the immunotoxicity of MCs is primarily characterized by the inhibition of PP1 and PP2A, oxidative stress, immune cell damage, and inflammation, as well as apoptosis. The advances in fish immunoreaction upon encountering MCs will benefit the monitoring and prediction of fish health, helping to achieve an ecotoxicological goal and to ensure the sustainability of species. Future studies concerning MC-induced immunotoxicity should focus on adaptive immunity, the hormesis phenomenon and the synergistic effects of aquatic microbial pathogens. Full article

(This article belongs to the Special Issue Ecology and Toxicology of Cyanobacteria and Cyanotoxins)

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