Hunting Down the Eagle Killer – Investigations into the Cyanotoxin Causing Avian Vacuolar Myelinopathy

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Avian Vacuolar Myelinopathy (AVM) is a fatal neurological disease of birds observed with an increasing frequency in the south-eastern United States. Its alarming spread during the last 25 years has raised concerns about avian populations, including the iconic bird of prey, the bald eagle. All evidence points at AVM being caused by a novel cyanobacterial toxin that is produced by cyanobacteria of the novel species and genus Aetokthonos hydrillicola, growing epiphytic on aquatic plants and travelling up the food chain, finally causing the typical brain lesions observed in AVM affected birds.We could isolate the toxigenic cyanobacterium and bring it in culture. The compound that is most likely causing AVM has been isolated and its structure has been elucidated. The aims of the presented project are - to finalize the structure elucidation of the putative cyanotoxin, and to confirm if it is indeed the agent causing AVM,- to sequence the cyanobacterial genome, to identify the biosynthesis gene cluster of the compound, and to characterize the biosynthesis in more detail,- to study the factors driving toxin biosynthesis and its kinetics, assess the water composition of affected lakes, and characterize the interaction between host plants and the cyanobacterium,- to develop specific PCR/qPCR markers and protocols to routinely detect the cyanotoxin producers in environmental samples,- to study uptake and localization of the toxin in zebrafish, and - to characterize an additional cytotoxic compound produced by A. hydrillicola and to identify its putative biosynthesis gene cluster.The project thus contributes to - the understanding of the etiology of AVM, - the identification and bioactivity characterization of a novel cyanotoxin- the chemical characterization of a recently discovered cyanobacterial genus,- the elucidation of the biosynthesis of a structurally intriguing specialized metabolite,- the development of methods for the routine monitoring of the toxin and its producer.In order to be able to asses if the novel cyanotoxin might be a threat for freshwater ecosystems or even human health, it is mandatory to gain a better understanding of the cyanobacterial toxin, its production, the role it plays in inducing AVM, and its biological activity in general.The development of detection and monitoring techniques for this dangerous toxin is of a great importance for wildlife protection, water management, and environmental safety. Moreover, the chemical, biochemical, and molecular (genetic) data will provide important insights for natural product research, biotechnology, and synthetic biology. The potent bioactivity of the compound under study, its unique chemical structure, and its possible selective toxicity may offer a new scaffold for drug discovery and pharmaceutical research in the future.