Itzhack Polacheck, PhD, Department of Clinical Microbiology & Infectious Diseases, Faculty of Medicine, The Hebrew University of Jerusalem and Hadassah University Hospital.
Background
Oomycetes (water molds) such as Saprolegnia, Branchiomyces and Aphanomyces are responsible for devastating infections of fish in aquaculture, fish farms and hobby fish tanks. Members of the genus Saprolegnia cause saprolegniosis, a disease that is characterized by visible white or grey patches of filamentous mycelium on the body or fins of freshwater fish. If untreated, infection with Saprolegnia species (spp.) leads to death by haemodilution. Infection frequently occurs during the winter, often resulting in large-scale "winter kill" epidemics.
Saprolegnia infections were controlled with Malachite Green, the most effective fungicide for saprolegniasis treatment. However, due to evidence of its carcinogenic, mutagenic, and teratogenic effects, its use has been severely prohibited in many countries including Israel. So far, there is no effective alternative treatment for this infection, and as S. parasitica infections are second only to bacterial diseases, the result is significant economic losses to aquaculture business worldwide.
Saprolegnia parasitica is one of the most economically damaging fish pathogens, causing losses of millions of dollars annually worldwide, particularly in the salmon and trout markets.
It is therefore of utmost importance to find new modes of treatment for this pathogen in order to avoid significant economic damages in cold regions.
Market
Saprolegnia parasitica causes tens of million dollar losses to aquaculture business worldwide, notably in Scotland, Scandinavia, Chile, Japan, Canada, Israel and the USA. In Japan, there is an annual mortality rate of 50% in Coho Salmon and Elver due to S. parasitica infections. In the United States, "winter kill" in Catfish caused by Saprolegnia results in financial loses of up to 50%, which represents an economic loss of $40 million. In Scotland, Saprolegniosis also causes significant losses with the main problem occurring in Salmon hatcheries. Therefore, there is an urgent need to find an effective alternative To Malachite Green for the management of Saprolegniasis.
The Innovation
In the course of our search for an alternative to Malachite Green treatment for fish-Saprolegniasis, a few Fluorescent Brighteners (diaminostilbene derivatives compounds) were tested for their anti-Saprolegnia activity. We hypothesize that these compounds bind and interfere with further synthesis of Saprolegnia cell wall cellulose or have effect on the integrity of the cell wall that does not confer enough strength to guarantee cell survival. In vitro susceptibility tests indicated that S. parasitica T-1 was susceptible to Blankophor BA (Minimal Inhibitory Concentration (MIC) =100 mg/L). This compound exhibited low toxicity for Tilapia (high LC50 value >1,000 mg/L, at 25, 18 and 15°C) and it was highly effective in prevention of Saprolegnia infection in the Tilapia-Saprolegniasis model, even at a low dosage of 25 mg/L. The effective concentration was lower than the MIC value.
The infected untreated high therapeutic index of Blankophor BA in combination with its documented safety to mammals and environment and its low cost, indicate that the treatment with Blankophor BA for fish Saprolegniasis could be an excellent alternative for Malachite Green.
R&D Program
- Study the hypothesis that disruption of cell wall is the mechanism of action of Blankophor against Oomycetes, by using chemical, molecular and morphological approaches.
- Development of fluorescent analytical method for the determination of the residual concentration of free Blankophor in the Fish and water.
- Field trials of prevention and/ or treatment of fish in large ponds.
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
