Chen, Chang-Shi, Georghiou, Sophia, Platzer, Edward G., Kao, Cheng-Yuan, Kelleher, Alan, Aroian, Raffi V., Hu, Yan
[
International Worm Meeting,
2009]
Soil-transmitted nematodes, hookworm, Ascaris, and Trichuris (HAT), are amongst the most prevalent human parasites, infecting more than 1 billion of the poorest peoples around the world. We have limited number drugs for treating these parasites, and, for practical reasons, only one (albendazole) is commonly used in mass drug administration (MDA). All our current drugs have limitations as used in MDAs, including moderate efficacy against hookworms, low efficacy against Trichuris, and threat of drug resistance. Therefore there is need for new human anthelmintics (anti-worm drugs) that are safe, effective and broad spectrum in scope. Our laboratory is working to develop Crystal (Cry) proteins produced by soil bacteria Bacillus thuringiensis (Bt) as a new class of anthelmintics. Bt Cry proteins are commonly used as insecticides in agriculture, are safe to humans, and have a mechanism of action (form pores in invertebrate intestine) different from nematicides currently use. Several Cry proteins have been identified that target nematodes, including C. elegans and plant-parasites. We are now using the mouse intestinal parasitic nematode, Heligmosomoides polygyrus, as a model for human disease. Here we will present our latest data showing the efficacy of Cry proteins against this rodent parasitic nematode, as well as our system to improve the anthelmintic activity of Cry proteins by looking for point mutant Cry variants that are hyperactive against C. elegans.