First European Multi-Lake Survey on cyanotoxins published !

Article by Evanthia Mantzouki and Bas Ibelings, Univ. of Geneva.

The first product of the European Multi Lake Survey (EMLS) is published in Toxins. This paper would not have been possible without the EMLS, the grassroots initiative that brought together around 200 scientists from 26 European countries to sample their lakes and answer questions of ecological importance. Understanding global scale phenomena, such as climate warming, requires information of high spatial resolution to investigate if lakes of similar characteristics (e.g. morphometry, trophic status) would respond in a consistent manner to similar environmental forcing. Cyanobacterial occurrence as a typical consequence of environmental perturbation in aquatic systems worldwide, was the centre of attention in the EMLS. Starting from a common goal to produce adequate evidence and eventually push for stricter regulation towards improved freshwater quality, the EMLS consortium (Figure 1) designed straightforward sampling protocols to accommodate the capacity in funding, time, personnel and equipment of all participants, without compromising quality. Cyanotoxins, phytoplankton pigments and environmental parameters were sampled and analysed in a fully standardised way to ensure scientific validity.

As a result of this effort, the first peer-reviewed EMLS article casts light on cyanotoxins and toxin quota distribution across the European continent. In an unexpected -but welcoming for our research purpose!- hot summer in 2015, temperature effects, both directly through boosting physiological processes of cyanobacterial growth and, indirectly through enhancing water stability that facilitate buoyant cyanobacterial cells, determined the spatial distribution of hepatotoxins (microcystins), neurotoxins (anatoxin-a) and cytotoxins cylindrospermopsin). The Northern European lakes were struck by a prolonged heat wave, more than the Mediterranean ones, during the sampling period that pinpointed the reality of climate warming. In such an event, toxin diversity increased along the latitudinal gradient, showing that cyanobacterial toxin production is enhanced not necessarily when it is hot (Mediterranean) but when it gets warmer than usual (heat event in North). Increases in toxin diversity (increase in toxin numbers but also representation of each toxin), entailed an increased presence of cylindrospermopsin, anatoxin and less studied microcystin variants, with a simultaneous decrease in the famous MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.

Reference (Open access):

Mantzouki et al. (2018). Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins. Toxins 2018, 10(4), 156;

EMLS was supported by COST Actions NETLAKE and CYANOCOST.


Breaking news: New type of photosynthesis discovered in cyanobacteria

From the report by Hayley Dunning in (15 June 2018):

“The discovery, published today in Science, was led by Imperial College London, supported by the BBSRC, and involved groups from the ANU in Canberra, the CNRS in Paris and Saclay and the CNR in Milan.

The vast majority of life on Earth uses visible red light in the process of photosynthesis, but the new type uses near-infrared light instead. It was detected in a wide range of cyanobacteria (blue-green algae) when they grow in near-infrared light, found in shaded conditions like bacterial mats in Yellowstone and in beach rock in Australia.

As scientists have now discovered, it also occurs in a cupboard fitted with infrared LEDs in Imperial College London.

The discovery changes our understanding of the basic mechanism of photosynthesis and should rewrite the textbooks.”


D.J. Nürnberg, J. Morton, S. Santabarbara, A. Telfer, P. Joliot, L. A. Antonaru, A. V. Ruban, T. Cardona, E. Krausz, A. Boussac, A. Fantuzzi and A. William Rutherford (2018). Photochemistry beyond the red limit in chlorophyll f–containing photosystems. Science  15 Jun 2018: Vol. 360, Issue 6394, pp. 1210-1213. DOI: 10.1126/science.aar8313

Cylindrospermopsin review paper acknowledging CYANOCOST, included in collection on Planetary Health.

Planetary Health is a relatively recent concept that aims to establish connections between the state of Earth’s natural systems and human health and well-being, thereby providing a broad perspective for environmental research and its importance to public health. ESPI’s Associate Editor Paul Tratnyek and Guest Editor Joe Needoba  have compiled a collection of ESPI papers with strong relevance to planetary health. In making their selections, the editors identified papers that address one or more “planetary boundaries”, which are the global-scale environmental threats that pose the greatest risk of disrupting Earth’s natural life support systems.

The paper “A review on cylindrospermopsin: The global occurrence, detection, toxicity and degradation of a potent cyanotoxin” by de la Cruz et al. has been selected for inclusion in the Editor’s Choice web collection on Planetary Health. The collection is introduced by Paul and Guest Editor Joseph Needoba (OHSU-PSU) in their Editorial, and you can read all the papers included at

This review paper on cylindrospermopsin is a product from a multi-national group of authors affiliated to academic organizations and agencies in USA, Cyprus and Greece. The paper acnowledges CYANOCOST.


de la Cruz, A. A., Hiskia, A., Kaloudis, T., Chernoff, N., Hill, D., Antoniou, M. G., He, X., Loftin, K., O’Shea, K., Zhao, C., Pelaez, M., Han, C., Lynch, T. J., & Dionysiou, D. D. (2013). A review on cylindrospermopsin: the global occurrence, detection, toxicity and degradation of a potent cyanotoxin. Environmental Science: Processes & Impacts, 15(11), 1979-2003.


Short Total Synthesis of [15N5]-Cylindrospermopsins from 15NH4Cl Enables Precise Quantification of Freshwater Cyanobacterial Contamination


From the abstract of a recent parer by Mailyan et al., published in JACS:

“Fresh water cyanobacterial algal blooms represent a major health risk because these organisms produce cylindrospermopsin, a toxic, structurally complex, zwitterionic uracil-guanidine alkaloid recognized by the EPA as a dangerous drinking water contaminant. At present, the ability to detect and quantify the presence of cylindrospermospin in water samples is severely hampered by the lack of an isotopically labeled standard for analytical mass spectrometry. Herein, we present a concise, scaled total synthesis of 15N cylindrospermosin from 15N ammonium chloride, which leverages a unique stereoselective intramolecular double conjugate addition step to assemble the tricyclic guanidine core. In addition to providing the first pure isotopically labeled probe for precise quantification of this potent biotoxin in fresh water sources, our results demonstrate how unique constraints associated with isotope incorporation compel novel solutions to synthesis design.”


Artur K. Mailyan, Joanna L. Chen, Weiwei Li, Arturo A. Keller, Shawn M. Sternisha, Brian G. Miller, and Armen ZakarianShort (2018). Total Synthesis of [15N5]-Cylindrospermopsins from 15NH4Cl Enables Precise Quantification of Freshwater Cyanobacterial Contamination. Journal of the American Chemical Society 2018 140 (18), 6027-6032. DOI: 10.1021/jacs.8b03071

Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel

From the abstract of a recent paper by Anat Lodin-Friedman and Shmuel Carmeli, published in Marine Drugs:

“During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10), were isolated from the extract of a bloom material of Microcystis sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey’s and advance Marfey’s methods and by comparison of 1H and 13C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by N-methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC50) values”.


Lodin-Friedman, A.; Carmeli, S. Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel. Mar. Drugs 2018, 16, 78.

Useful resources for the HABs season – EPA Freshwater HABs Newsletter

The May 2018 issue of the US EPA Freshwater HABs Newsletter is published.

It features, among others, a list of tools and resources for the HABs season. The list of resources is useful for drinking water supplies, bathing water authorities and the general public.

You can download the newsletter here.

For subscription to the newsletter, comments, feedback or additional information, you can contact Lesley D’Anglada.

Do not drink the tap water ! City of Salem, Oregon, May 29.

The City of Salem, Oregon USA, has issued a drinking water advisory on May 29, related to the presence of cylindrospermopsin and microcystin in the water supplies. The cyanotoxins originate from the Detroit Reservoir that is used as source.

The advisory concerns infants, young children and other vulnerable individuals, stating that “children under the age of six, people with compromised immune systems, people receiving dialysis treatment, people with pre-existing liver conditions, pets, pregnant women or nursing mothers, or other sensitive populations should follow this advisory. At this time, people not on this list may continue to drink the water unless additional messaging is received.”

Updates of the advisory will follow on .


Uptake and accumulation of MC-LR based on exposure through drinking water: An animal model assessing the human health risk

From the abstract of a recent paper by Greer et al. in Scientific Reports:

To understand the uptake and processing of MC-LR in humans, the pig was chosen as an animal model. This was assessed by repeated exposure for 13 weeks of eight animals dosed daily with MC-LR at 0.04 µg/kg bw, repeated with six animals over five weeks at a dose 50 times higher at 2 µg/kg bw. An analytical method was developed for MC-LR in porcine serum and also to analyse levels of free MC-LR in harvested porcine tissues, with Lemieux Oxidation employed to determine bound MC-LR in these tissues. MC-LR was not detected in the serum of treated animals from either experiment but free MC-LR was observed in the large intestine and kidney from two animals from the higher dosed group at levels of 1.4 and 1.9 µg/kg dry weight (dw) respectively. The results indicated 50% of higher dosed animals accumulated bound MC-LR in liver tissue, averaging 26.4 µg, approximately 1.1% of the dose administered. These results point to the potential uptake and accumulation of MC-LR in human liver tissue exposed chronically to sub-acute doses.”


Brett Greer, Julie P. Meneely & Christopher T. Elliott (2018). Uptake and accumulation of Microcystin-LR based on exposure through drinking water: An animal model assessing the human health risk. Scietific Reports 8, 4913. DOI:10.1038/s41598-018-23312-7


New research shows that 2,4-DABA induces irreversible functional changes in neurons.

From the abstract of a recent paper by Spacic et al. in Aquatic Toxicology:

“In this paper we present, for the first time, a detailed account of electrophysiological effects of 2,4-diaminobutyric acid (2,4-DABA). 2,4-DABA is a neurotoxic non-protein amino acid produced by Cyanobacteria with a possible link to neurodegenerative disorders in animals and humans. Intracellular recordings were performed on Retzius nerve cells of the leech Haemopis sanguisuga using glass microelectrodes filled with 3 mol/L KCl. Our results show that 2,4-DABA is an excitatory amino acid, causing membrane depolarization in a concentration dependent manner. The most prominent depolarizations of 39.63 ± 2.22 mV and 47.05 ± 4.33 mV, induced by 5 × 10−3 and 10−2 mol/L 2,4-DABA respectively, are several times larger than maximal depolarizations induced by either Glutamate, Aspartate, β-N-methylamino-alanine (BMAA) or β-N-oxalylamino-alanine (BOAA) on our model. These 2,4-DABA induced depolarizations evolve through two distinct stages, which is a novel phenomenon in electrical cell activity upon application of an excitatory amino acid, at least on our model. Involvement of two separate mechanisms, suggested by the two stage phenomenon, is discussed in the paper. We also provide evidence that 2,4-DABA induces irreversible functional disturbances in neurons in a concentration dependent manner, since only half of the cells recovered normal electrical activity after application of 5 × 10−3 mol/L 2,4-DABA, and none recovered after application of 10−2 mol/L 2,4-DABA. Effects of both L-2,4-DABA and DL-2,4-DABA were tested and are not significantly different.”


S. Spasic, M. Stanojevic, J. Nesovic Ostojic, S. Kovacevic, M. Prostran, S. Lopicic (2018).
Extensive depolarization and lack of recovery of leech Retzius neurons caused by 2,4 diaminobutyric acid. Aquatic Toxicology, Volume 199, Pages 269-275.

The paper acknowledges CYANOCOST.

Genotoxic potential of the binary mixture of cyanotoxins microcystin- LR and cylindrospermopsin

From the abstract of a recent paper by Hercog et al. in Chemosphere:

“Increased eutrophication of water bodies promotes cyanobacterial blooming that is hazardous due to the production of various bioactive compounds. Microcystin-LR (MCLR) is among the most widespread cyanotoxins classified as possible human carcinogen, while cylindrospermopsin (CYN) has only recently been recognized as health concern. Both cyanotoxins are genotoxic; however, the mechanisms of their action differ. They are ubiquitously present in water environment and are often detected together. Therefore, we studied genotoxic potential of the binary mixture of these cyanotoxins. Human hepatoma cells (HepG2) were exposed to a single dose of MCLR (1 μg/mL), graded doses of CYN (0.01-0.5 μg/mL), and their combinations. Comet and Cytokinesis block micronucleus assays were used to detect induction of DNA strand breaks (sb) and genomic instability, respectively, along with the transcriptional analyses of the expression of selected genes involved in xenobiotic metabolism, immediate/early cell response and DNA-damage response. MCLR induced DNA sb that were only transiently present after 4 h exposure, whereas CYN, after 24 h exposure, induced DNA sb and genomic instability. The MCLR/CYN mixture induced DNA sb after 24 h exposure, but to lesser extent as CYN alone. On the other hand, induction of genomic instability by the MCLR/CYN mixture was comparable to that induced by CYN alone. In addition, patterns of changes in the expression of selected genes induced by the MCLR/CYN mixture were not significantly different from those induced by CYN alone. Our results indicate that CYN exerts higher genotoxic potential than MCLR and that genotoxic potential of the MCLR/CYN mixture is comparable to that of CYN alone.”


Klara Hercog, Sara Maisanaba, Metka Filipič, Ángeles Jos, Ana M. Cameán, Bojana Žegura (2017). Genotoxic potential of the binary mixture of cyanotoxins microcystin-LR and cylindrospermopsin, Chemosphere, Volume 189, Pages 319-329,