Parasitology
Molecular basis of anthelmintic resistance in parasitic
nematodes and development of rapid detection systems
Skuce, P
Anthelmintics are pivotal to the control of parasitic infections in intensively farmed livestock and, in the absence of any realistic alternatives, are likely to remain so for the foreseeable future. However, this situation is being threatened by the emergence of parasites that are resistant to all the commonly used anthelmintics. Indeed, we have recently identified several isolates of multi-drug resistant parasites on local Scottish sheep farms. This is a worrying development. Existing lab-based tests for resistance are too labour intensive and insensitive to detect resistant parasites when they are at a low level in the population. Molecular (genetic) tests would be considerably more sensitive and specific and could be applied at the individual parasite level e.g. eggs, larvae, adults. Current opinion suggests that resistance arises through changes (mutations) in candidate "resistance genes" that allow parasites to survive treatment and that are inherited by subsequent generations. These genes typically encode the drug's main target within the parasite or the parasite's drug pumping mechanisms. We have identified several of the key "resistance genes" from our species and are in the process of comparing susceptible and resistant worms to see what has changed at the molecular level in resistant parasites. The current project aims to establish the molecular methodologies required to detect these changes in our most important species (Haemonchus and Teladorsagia). We will then use this information to develop sensitive, specific, high throughput tests for resistance using state-of-the-art gene sequencing technologies.