UK researchers have pinpointed how drug resistance emerges in a parasitic worm, providing crucial data for tracking resistant variants in the field.
Researchers used genetic crosses, drug selection and whole genome sequencing to map the genes linked to drug resistance of the parasitic worm, Haemonchus contortus, for the first time.
Drug resistance in parasitic worms poses a serious threat to global efforts to limit the significant health and economic impacts they have on livestock.
In the new study, published in Cell Reports, the team identified a handful of new and known genetic variants for three of the most important drugs used for parasitic worm control.
They pinpointed how drug resistance emerges and providing crucial data for the tracking of resistant variants in the field.
The research, from the Wellcome Sanger Institute, the University of Glasgow and the Moredun Research Institute, lays the foundations for understanding how drug resistance arises and, most importantly, how it can be controlled.
Haemonchus contortus, known as the barber’s pole worm for its distinctive candy-stripe markings, is a species of parasitic worm known as a helminth.
Helminths infects livestock, with countless animals requiring treatment with drugs to control infections each year. Left untreated, infections can result in significant production loss and death.
But widespread resistance to anthelmintic drugs means that in many places certain drugs are ineffective. In the worst-case scenario, some farms harbour parasites resistant to every available treatment.
Drug resistance threatens to add to the already huge costs of helminth infections of livestock, which are responsible for annual production losses of €686 million in Europe alone.
In this new study, scientists set out to discover the genetic basis of drug resistance in H. contortus to the three most important anthelmintic drug classes used to control helminths in both humans and animals.
To pinpoint the genes involved, the Moredun Research Institute crossed drug-susceptible and multidrug-resistant strains of the parasite, followed by drug treatment using either fenbendazole, levamisole or ivermectin.
Whole genome sequencing of the crossed parasites was undertaken at the Wellcome Sanger Institute.
Analysis of the genomes of parasites sampled before and after drug treatment, together with genomic data from parasites sampled around the world, allowed the researchers to pinpoint a small number of new and known genes implicated in drug resistance.
Molecular and drug treatment analyses using the free-living model worm Caenorhabditis elegans at the University of Glasgow further validated the genomic findings.
Dr Roz Laing, from the University of Glasgow, said helminth infections had a huge economic and health burden in the UK and across the world.
"In people and animals, treatment relies on a small number of anthelmintic drugs, all of which were initially developed for veterinary use," Dr Laing said.
"Alarmingly, we now see widespread resistance to these drugs in livestock and pets, highlighting a need for more strategic use and earlier detection of resistance to maintain drug efficacy.
"Identifying the genes involved in resistance to three different drugs in an economically important species like Haemonchus contortus is an important step forward.”
