Co-Occurrence of Cyanobacteria and Cyanotoxins with Other Environmental Health Hazards:Impacts and Implications

Toxin-producing cyanobacteria in aquatic, terrestrial, and aerial environments can occur alongside a wide range of additional health hazards including biological agents and synthetic materials. Cases of intoxications involving cyanobacteria and cyanotoxins, with exposure to additional hazards, are discussed. Examples of the co-occurrence of cyanobacteria in such combinations are reviewed, including cyanobacteria and cyanotoxins plus algal toxins, microbial pathogens and fecal indicator bacteria, metals, pesticides, and microplastics. Toxicity assessments of cyanobacteria, cyanotoxins, and these additional agents, where investigated in bioassays and in defined combinations, are discussed and further research needs are identified.</p

Co-occurrence of taste and odor compounds and cyanotoxins in cyanobacterial blooms:emerging risks to human health?

Cyanobacteria commonly form large blooms in waterbodies; they can produce cyanotoxins, with toxic effects on humans and animals, and volatile compounds, causing bad tastes and odors (T&amp;O) at naturally occurring low concentrations. Notwithstanding the large amount of literature on either cyanotoxins or T&amp;O, no review has focused on them at the same time. The present review critically evaluates the recent literature on cyanotoxins and T&amp;O compounds (geosmin, 2-methylisoborneol, β-ionone and β-cyclocitral) to identify research gaps on harmful exposure of humans and animals to both metabolite classes. T&amp;O and cyanotoxins production can be due to the same or common to different cyanobacterial species/strains, with the additional possibility of T&amp;O production by non-cyanobacterial species. The few environmental studies on the co-occurrence of these two groups of metabolites are not sufficient to understand if and how they can co-vary, or influence each other, perhaps stimulating cyanotoxin production. Therefore, T&amp;Os cannot reliably serve as early warning surrogates for cyanotoxins. The scarce data on T&amp;O toxicity seem to indicate a low health risk (but the inhalation of β-cyclocitral deserves more study). However, no data are available on the effects of combined exposure to mixtures of cyanotoxins and T&amp;O compounds and to combinations of T&amp;O compounds; therefore, whether the co-occurrence of cyanotoxins and T&amp;O compounds is a health issue remains an open question.</p

Genomic insights into the biosynthesis and physiology of the cyanobacterial neurotoxin 2,4-diaminobutanoic acid (2,4-DAB)

Cyanobacteria are an ancient clade of photosynthetic prokaryotes, whose worldwide occurrence, especially in water, presents health hazards to humans and animals due to the production of a range of toxins (cyanotoxins). These include the sometimes co-occurring, non-encoded diaminoacid neurotoxins 2,4-diaminobutanoic acid (2,4-DAB) and its structural analogue β-N-methylaminoalanine (BMAA). Knowledge of the biosynthetic pathway for 2,4-DAB, and its role in cyanobacteria, is lacking. The aspartate 4-phosphate pathway is a known route of 2,4-DAB biosynthesis in other bacteria and in some plant species. Another pathway to 2,4-DAB has been described in Lathyrus species. Here, we use bioinformatics analyses to investigate hypotheses concerning 2,4-DAB biosynthesis in cyanobacteria. We assessed the presence or absence of each enzyme in candidate biosynthesis routes, the aspartate 4-phosphate pathway and a pathway to 2,4-DAB derived from S-adenosyl-L-methionine (SAM), in 130 cyanobacterial genomes using sequence alignment, profile hidden Markov models, substrate specificity/active site identification and the reconstruction of gene phylogenies. In the aspartate 4-phosphate pathway, for the 18 species encoding diaminobutanoate-2-oxo-glutarate transaminase, the co-localisation of genes encoding the transaminase with the downstream decarboxylase or ectoine synthase – often within hybrid non-ribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) clusters, NRPS-independent siderophore (NIS) clusters and incomplete ectoine clusters – is compatible with the hypothesis that some cyanobacteria use the aspartate 4-phosphate pathway for 2,4-DAB production. Through this route, in cyanobacteria, 2,4-DAB may be functionally associated with environmental iron-scavenging, via the production of siderophores of the schizokinen/synechobactin type and of some polyamines. In the pathway to 2,4-DAB derived from SAM, eight cyanobacterial species encode homologs of SAM-dependent 3-amino-3-carboxypropyl transferases. Other enzymes in this pathway have not yet been purified or sequenced. Ultimately, the biosynthesis of 2,4-DAB appears to be either restricted to some cyanobacterial species, or there may be multiple and additional routes, and roles, for the synthesis of this neurotoxin.</p

Genomic insights into the biosynthesis and physiology of the cyanobacterial neurotoxin 3-N-methyl-2,3-diaminopropanoic acid (BMAA)

Cyanobacteria are an ancient clade of photosynthetic prokaryotes, present in many habitats throughout the world, including water resources. They can present health hazards to humans and animals due to the production of a wide range of toxins (cyanotoxins), including the diaminoacid neurotoxin, β-N-methylaminoalanine (BMAA). Knowledge of the biosynthetic pathway for BMAA, and its role in cyanobacteria, is lacking. Present evidence suggests that BMAA is derived by 3-N methylation of 2,3-diaminopropanoic acid (2,3-DAP) and, although the latter has never been reported in cyanobacteria, there are multiple pathways to its biosynthesis known in other bacteria and in plants. Here, we used bioinformatics analyses to investigate hypotheses concerning 2,3-DAP and BMAA biosynthesis in cyanobacteria. We assessed the potential presence or absence of each enzyme in candidate biosynthetic routes known in Albizia julibrissin, Lathyrus sativus seedlings, Streptomyces, Clostridium, Staphylococcus aureus, Pantoea agglomerans, and Paenibacillus larvae, in 130 cyanobacterial genomes using sequence alignment, profile hidden Markov models, substrate specificity/active site identification and the reconstruction of gene phylogenies. Most enzymes involved in pathways leading to 2,3-DAP in other species were not found in the cyanobacteria analysed. Nevertheless, two species appear to have the genes sbnA and sbnB, responsible for forming the 2,3-DAP constituent in staphyloferrin B, a siderophore from Staphylococcus aureus. It is currently undetermined whether these species are also capable of biosynthesising BMAA. It is possible that, in some cyanobacteria, the formation of 2,3-DAP and/or BMAA is associated with environmental iron-scavenging. The pam gene cluster, responsible for the biosynthesis of the BMAA-containing peptide, paenilamicin, so far appears to be restricted to Paenibacillus larvae. It was not detected in any of the cyanobacterial genomes analysed, nor was it found in 93 other Paenibacillus genomes or in the genomes of two BMAA-producing diatom species. We hypothesise that the presence, in some cyanobacterial species, of the enzymes 2,3-diaminopropionate ammonia-lyase (DAPAL) and reactive intermediate deaminase A (RidA) may explain the failure to detect 2,3-DAP in analytical studies. Overall, the taxonomic distribution of 2,3-DAP and BMAA in cyanobacteria is unclear; there may be multiple and additional routes, and roles, for the biosynthesis of 2,3-DAP and BMAA in these organisms.Output Status: Forthcoming/Available Onlin

Hyperspectral remote sensing of cyanobacterial pigments as indicators for cell populations and toxins in eutrophic lakes

The growth of mass populations of toxin-producing cyanobacteria is a serious concern for the ecological status of inland waterbodies and for human and animal health. In this study we examined the performance of four semi-analytical algorithms for the retrieval of chlorophyll a (Chl a) and phycocyanin (C-PC) from data acquired by the Compact Airborne Spectrographic Imager-2 (CASI-2) and the Airborne Imaging Spectrometer for Applications (AISA) Eagle sensor. The retrieval accuracies of the semi-analytical models were compared to those returned by optimally calibrated empirical band-ratio algorithms. The best-performing algorithm for the retrieval of Chl a was an empirical band-ratio model based on a quadratic function of the ratio of re!ectance at 710 and 670 nm (R2=0.832; RMSE=29.8%). However, this model only provided a marginally better retrieval than the best semi-analytical algorithm. The best-performing model for the retrieval of C-PC was a semi-analytical nested band-ratio model (R2=0.984; RMSE=3.98 mg m−3). The concentrations of C-PC retrieved using the semi-analytical model were correlated with cyanobacterial cell numbers (R2=0.380) and the particulate and total (particulate plus dissolved) pools of microcystins (R2=0.858 and 0.896 respectively). Importantly, both the empirical and semi-analytical algorithms were able to retrieve the concentration of C-PC at cyanobacterial cell concentrations below current warning thresholds for cyanobacteria in waterbodies. This demonstrates the potential of remote sensing to contribute to early-warning detection and monitoring of cyanobacterial blooms for human health protection at regional and global scales

Grazing livestock are exposed to terrestrial cyanobacteria

While toxins from aquatic cyanobacteria are a well-recognised cause of disease in birds and animals, exposure of grazing livestock to terrestrial cyanobacteria has not been described. This study identified terrestrial cyanobacteria, predominantlyPhormidiumspp., in the biofilm of plants from most livestock fields investigated. Lower numbers of other cyanobacteria, microalgae and fungi were present on many plants. Cyanobacterial 16S rDNA, predominantly fromPhormidiumspp., was detected in all samples tested, including 6 plant washings, 1 soil sample and ileal contents from 2 grazing horses. Further work was performed to test the hypothesis that ingestion of cyanotoxins contributes to the pathogenesis of some currently unexplained diseases of grazing horses, including equine grass sickness (EGS), equine motor neuron disease (EMND) and hepatopathy.Phormidiumpopulation density was significantly higher on EGS fields than on control fields. The cyanobacterial neurotoxic amino acid 2,4-diaminobutyric acid (DAB) was detected in plant washings from EGS fields, but worst case scenario estimations suggested the dose would be insufficient to cause disease. Neither DAB nor the cyanobacterial neurotoxins &beta;-N-methylamino-L-alanine and N-(2-aminoethyl) glycine were detected in neural tissue from 6 EGS horses, 2 EMND horses and 7 control horses.Phormidiumwas present in low numbers on plants where horses had unexplained hepatopathy. This study did not yield evidence linking known cyanotoxins with disease in grazing horses. However, further study is warranted to identify and quantify toxins produced by cyanobacteria on livestock fields, and determine whether, under appropriate conditions, known or unknown cyanotoxins contribute to currently unexplained diseases in grazing livestock

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer