Promise of Bacillus thuringiensis Crystal Proteins as Anthelmintics

Abstract

Bacillus thuringiensis crystal (Cry) proteins are the most widely used biological insecticides in the world. Their value in safely controlling insects that destroy crops and transmit human diseases is well established. Here, we review B. thuringiensis Cry proteins as novel anthelmintics with a unique mode of action. In laboratory studies, Cry proteins are highly effective against a broad range of free-living roundworms and parasitic roundworms that infect plants and animals. Cry5B is therapeutic for two different intestinal roundworm parasitic infections – one in mice and the other in hamsters. The latter infection involves a minor hookworm parasite of humans, Ancylostoma ceylanicum, which is closely related to the more prevalent Ancylostoma duodenale. Therapy is observed despite the fact that much of the protein is likely degraded in the stomach prior to reaching the parasites. Cry21A is also therapeutic in mice infected with the roundworm parasite, Heligmosomoides bakeri. Cry proteins offer excellent combinatorial therapeutic properties with nicotinic acetylcholine receptor agonists – one of two classes of compounds approved by the World Health Organization for treatment of intestinal roundworms in humans. Given their nontoxicity to humans and their broad spectrum of nematicidal action, Cry proteins show great potential as next-generation anthelmintics.