Ivermectin is a major drug used to control human diseases caused by filarial nematodes, but we do not fully understand how the drug works to reduce transmission of the parasites from infected people to the insect vectors. We infected gerbils with the human parasite Brugia malayi and treated them once with ivermectin at a dose equivalent to those given to people in endemic regions. RNASeq analysis identified a number of genes whose expression was significantly altered in the parasites by the treatment. Forty-four of those genes have orthologs in the free-living species C. elegans for which mutant strains are available. We will test the effects of the mutations in these 44 genes on the response of C. elegans to ivermectin, focusing on the development, movement, feeding and reproduction of the worm. The assays for development and reproduction (egg- laying) are well-established and straightforward. To assess the effects of drug treatment on motility we will use a modified high definition video analysis on synchronized populations. Pharyngeal pumping will be measured the commercially available Nemametrix Screenchip system. We anticipate that this analysis will reveal new genes that contribute to the overall anthelmintic effect of ivermectin, and potentially open up new routes towards the development of novel control agents.
Ivermectin is an important drug used to control human infections with parasitic nematodes, but we don't understand exactly how it works. We have identified a collection of genes that may influence the way the drug works in a parasitic nematode, Brugia malayi, and will test these genes in a model organism, C. elegans. The results should yield new clues into how the drug removes parasites from infected people and perhaps suggest new ways
