Authors

Discussion

The highly contagious disease, psoroptic mange, is a significant welfare concern caused by a hypersensitivity response to the mite, Psoroptes ovis, which lives and feeds on the surface of the skin. Psoroptes ovis is a particular problem for sheep in the UK, where the condition is known as sheep scab, and cattle in Belgium, with host-adapted populations present in both countries. Following eradication from the UK in 1952, sheep scab was inadvertently reintroduced in 1973, suggesting that mite populations on different farms remain highly genetically similar today. Control requires quarantine, isolation from neighbouring flocks/herds and treatment of all animals on a holding during an outbreak. Two acaricide classes are available to treat or prevent infestation with P. ovis: an organophosphate dip, diazinon; and injectable macrocyclic lactones (MLs) notably moxidectin, doramectin and ivermectin. Resistance to the MLs was first reported in the UK in 2018 and has since been detected on multiple farms across the country. 

Our project seeks to understand the genetic basis of ML resistance, in particular to moxidectin, and identify whether resistance is spreading from farm to farm or arising independently on different farms. We have a recently curated chromosomal genome assembly, and two lab isolates - one ML-sensitive and one ML-resistant. The ML-sensitive isolate has been maintained for more than two decades, but underwent multiple additions prior to 2016. In contrast, the ML-resistant isolate was collected only in 2021 using a small number of mites from a farm in South West England where the mite population appeared to be resistant to all three MLs. 

Multiple genetic loci differ between the two isolates, therefore, to identify loci associated with moxidectin resistance, we performed genetic crosses followed by selection. Using whole genome sequencing of pools from two of these genetic crosses, and the parental isolates, we will show that five distinct loci across three chromosomes may confer resistance to moxidectin within this resistant isolate, both in vivo and in vitro. We will also describe the low nucleotide diversity within these two isolates, while highlighting the marked genetic differences between them at more than ten discrete genomic regions. The impact of these findings on ongoing work which aims to sequence the whole genome from individual mite lysates will be discussed in relation to the historical and current population structure and the spread of resistance markers.