The discovery is particularly relevant to global health, because of concerns about the potential emergence of resistance in human intestinal nematodes to currently available medicines.
"There are only a few new agents under development for the treatment of hookworm and other intestinal parasite infections," said Raffi Aroian, an associate professor of biology at UCSD and co-principal author of the study. "Crystal toxins are safe to humans, mammals and other vertebrates. And it might be possible to improve the efficacy of current treatments by giving a drug like mebendazole and Cry5B simultaneously."
Other authors of the study are Richard Bungiro and Lisa Harrison of the Yale medical school and Larry Bischof, Joel Griffitts and Brad Barrows of UCSD.
Aroian and his UCSD colleagues discovered five years ago that the roundworm C. elegans and other nematodes are susceptible to the effects of Cry5B, then known primarily as an insecticide. The toxin forms tiny holes in the membranes of the cells of nematodes and insects. However, since the toxin can't bind to the cells of mammals or other vertebrates, Cry proteins can't hurt humans.
"Crystal proteins had been used for decades to kill insects by organic farmers who sprayed their crops with Bt," said Aroian. "Until now, however, no one has used a purified Cry protein to treat a parasitic nematode."
Aroian met Cappello, a pediatric infectious diseases specialist who studies hookworm, at a meeting of the Burroughs-Wellcome Fund and decided to collaborate on a project to see if crystal proteins could be effective against hookworm infections. Three years ago, Aroian and his colleagues purified Cry5B toxin and sent it to Cappello, who then tested the compound in a laboratory model of hookworm inf
Source:University of California - San Diego