Cyanotoxins and microbial metabolites

Research

Cyanotoxins: microbial metabolites, useful reagents and water-borne health hazards

The cyanobacteria (blue-green algae) which occur globally in aquatic and terrestrial environments produce a wide range of potent toxins. These include hepato-, neuro-, and cytotoxins, carcinogens and tumour promoters.

We have demonstrated the role of these toxins in poisonings of domestic and wild animals, birds and fish in several countries and, with medical colleagues, have determined the role of cyanotoxins in human health incidents, from mild to fatal. Adverse human and animal health outcomes of exposure to cyanotoxins, their occurrence in water resources at concentrations above health guideline values, and toxicity assessments, together indicate that they can be among the most hazardous natural products in aquatic environments. This laboratory participates in UK and international working parties to devise and implement procedures to reduce the risks presented by cyanotoxins to water-users. We investigate a range of cyanotoxins and other cyanobacterial products in aquatic environments and in our culture collection of cyanobacteria, including cyclic heptapeptides (microcystins) and pentapeptides (nodularins), alkaloids (anatoxins, saxitoxins, cylindrospermopsins), lipopolysachharide (LPS) endotoxins and a neurotoxic amino acid ( b-N-methylamino-L-alanine; BMAA). Modes of action, including the inhibition of protein phosphatases, and of acetylcholinesterase, protein synthesis, proteases, ion channel blockage and DNA strand breakage, provide opportunities for the use of these products as research and analytical reagents and as templates for drug development.

Our current research includes the development of cyanotoxin detection and analytical methods and participation in international interlaboratory validation programmes. Antibodies are being produced and used to quantify and localise the toxins in the producer-cells and in exposed biota. Immuno- and fluorescent-in situ hybridisation methods are permitting toxin quantification in single filaments of cells and microcystin synthetase DNA detection in single cells. The cyanotoxins typically commonly occur in combination, rather than singly and interactions are being determined in influencing exposure outcomes. Research into the causes of mass mortalities of Lesser Flamingos at African lakes will be aided our discovery of cyanotoxins in the feathers of the birds, thereby permitting non-invasive investigations.

The significance of aquatic cyanobacteria as producers of BMAA is also being investigated. This is in relation to the possible contribution of BMAA to human neurodegenerative disease.

Collaboration with colleagues in Japan reminds us that cyanobacterial metabolites include numerous potentially useful products beside cyanotoxins: these include a novel phosphonate biosurfactant isolated from a cyanobacterial bloom from Scottish freshwaters.

Publications

Young, F.M., Morrison, L.F., James, J. and Codd, G.A.: Quantification and localisation of microcystins in colonies of a laboratory strain of Microcystis (Cyanobacteria) using immunological methods. European Journal of Phycology 43, 217-225 (2008).

Gurbuz, F. And Codd, G.A.: Microcystin removal by a naturally-occurring substance: pumice. Bulletin of Environmental Contamination and Toxicology 81, 323-327 (2008).

Purdie, E.L., Young, F.M., Menzel, D. and Codd, G.A.: A method for acetonitrile-free microcystin analysis and purificiation by high-performance liquid chromatography, using methanol as mobile phase. Toxicon 54, 887-890 (2009).

Lindsay, J., Metcalf, J.S. and Codd, G.A.: Comparison of four methods for the extraction of lipopolysaccharide from cyanobacteria. Toxicological & Environmental Chemistry 91, 1253-1262 (2009).

Purdie, E.L., Metcalf, J.S., Kashmiri, S. and Codd, G.A.: Toxicity of the cyanobacterial neurotoxin β-N-methylamino-L-alanine to three aquatic animal species. Amyotrophic Lateral Sclerosis 10, suppl. 2, 67-70 (2009).

Metcalf, J.S. and Codd, G.A.: Cyanobacteria, neurotoxins and water resources: are there implications for human neurodegenerative disease? Amyotrophic Lateral Sclerosis 10, suppl. 2, 74-78 (2009).

Cox, P.A., Richer, R., Metcalf, J.S., Banack, S.A., Codd, G.A. and Bradley, W.G.: Cyanobacteria and BMAA Exposure from desert dust: a possible link to sporadic ALS among Gulf War veterans. Amyotrophic Lateral Sclerosis 10, suppl. 2, 109-117 (2009).

Codd, G.A., Morrison, L.F., Nath, M., Sano, T. and Kaya, K.: Extraction of cyanostatins and their analysis with microcystins and anabaenopeptin-A, in a 21-year archive of cyanobacterial bloom samples. Algological Studies 130, 53-68 (2009).

Purdie, E.L., Samsudin, S., Eddy, F.B. and Codd, G.A.: Effects of the cyanobacterial neurotoxin β-N-methylamino-L-alanine on the early-life stage development of zebrafish (Danio rerio). Aquatic Toxicology 95, 279-284 (2009).

Metcalf, J.S., Reilly, M., Young, F.M. and Codd, G.A.: Localisation of microcystin synthetase genes in colonies of the cyanobacterium Microcystis using fluorescence in situ hybridisation. Journal of Phycology 45, 1400-1404 (2009).