Novel toxicity associated with a Limnothrix-like species : mouse bioassay results

Background & Aims: A search for novel cylindrospermopsin (CYN) producers found a Limnothrix strain that inhibited protein synthesis but did not contain detectable CYN or analogues (HPLC, LC-MS, ELISA), nor the CYN gene (Bernard et al 2010). Methods: Mouse bioassays (time-course up to seven days, and set times up to 24h) were performed followed by detailed post-mortem (PM) dissections and histopathology. By 3h, these reduced but clear mucoid diarrhoea (containing sloughed endothelium and blood cells) was observed. Body weights were reduced by 24h and remained below controls for 7d. Liver and spleen weights (% body weight) increased by 4h and remained high until at least 24h. Histopathology (10-24h) indicated cell death in the small intestine (widespread), liver and kidneys. White blood cell numbers increased in the circulation, spleen and lungs. Conclusions: Limnothrix produces a potent in vivo cytotoxin. It is water-extractable and produced by a commonly occurring genus. Hence it is a potential risk to drinking water sources. We are currently (1) clarifying the genetic identity of the toxic strain, (2) determining its Australian distribution, (3) purifying and characterising the active compound, and (4) investigating its mechanism of action post-mortem (PM) dissections and histopathology. Results: By 0.5h post-injection, signs included extreme sensitivity to touch and sudden noises, and hind limb weakness.