Understanding drug resistance in multicellular parasites

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The goal of our research program is to develop tools that will allow Canadian sheep and cattle producers to better cope with parasitic roundworm infections that commonly reduce the health and profitability of their stock. Grazing livestock are frequently infected with parasitic gastrointestinal roundworms that contaminate pastures. The disease caused by gastrointestinal roundworms ranges from mild, reducing growth and profitability, to severe, leading to the death of livestock. Until recently, producers were confident that they could successfully treat roundworm parasites with inexpensive, effective de-worming drugs, of which one of the most widely used is ivermectin. Ivermectin's importance in controlling parasite infections in both humans and livestock was reflected in the 2015 Nobel Prize awarded to the researchers who discovered it. Unfortunately, parasites are rapidly evolving resistance to ivermectin, threatening to reverse the health gains achieved through its use. If producers use ivermectin to treat livestock infected with resistant parasites, animals continue to suffer from parasites and the producer will have wasted time and money on an ineffective drug. An inexpensive, convenient diagnostic test would greatly improve the ability of producers to: 1) choose the most effective treatments, and 2) to manage herds in ways that minimize the perpetuation and spread of drug resistance. To develop such a test requires an understanding of the genetic basis of ivermectin resistance.***Because experiments on parasitic worms that live a sheep's or cow's stomach are challenging, we study drug resistance in a roundworm, Caenorhabditis elegans, that can easily be grown in the laboratory. We look for mutant strains that are resistant to ivermectin and identify the specific genetic changes that explain ivermectin resistance. What we learn from C. elegans usually applies to parasitic roundworms as well; parasites have similar resistance genes that are changed in similar ways to cause resistance. This was recently demonstrated by our discovery of a gene, dyf-7, that can mutate to make both C. elegans and the sheep parasite Haemonchus contortus resistant to ivermectin. However, we have reason to believe that there are many other genes involved in resistance, genes that we will identify in C. elegans. The genes we find will be incorporated into a genetic test for resistance in parasites that will help preserve ivermectin's legacy of protecting animal and human health.