Comparative proteome analysis of the midgut of Rhipicephalus microplus (Acari: Ixodidae) strains with contrasting resistance to ivermectin reveals the activation of proteins involved in the detoxification metabolism

Abstract

Rhipicephalus microplus is the most serious tick parasite for the livestock industry in tropical and subtropical regions. A cost-effective control method to manage the infestation of this parasite involves the use of chemicals such as ivermectin. However, massive overuse of ivermectin over recent decades has selected for ivermectin-resistant populations of R. microplus. Here, we carried out a comparative proteomic analysis of the midgut of ivermectin-susceptible versus ivermectin-resistant ticks using tandem mass tags coupled to synchronous precursor selection. In susceptible ticks, there was an over-representation of proteins associated with blood digestion and anticoagulation. In contrast, resistant ticks exhibited an over-accumulation of proteins involved in phase I and phase II of the detoxification metabolism, including cytochrome P450, glutathione-S-transferase, and ABC transporters, as well as many ribosomal and other translation-related proteins. This information provides new clues about the mechanisms of ivermectin resistance in R. microplus as well as suggesting potential novel molecular targets to cope with ivermectin-resistant populations of R. microplus. SIGNIFICANCE: Cattle farming is an important primary economic activity for food production all over the globe. However, this activity also has detrimental environmental impacts, including the overuse of ivermectin and other chemicals used to control parasite infestations. The overuse of ivermectin selected for parasites with resistance to this chemical, including tick species like R. microplus. There has been extensive to understand the mechanisms that mediate ivermectin resistance in arthropods, but many gaps remain for the full comprehension of this phenomenon. Understanding the biochemistry behind ivermectin resistance could provide new alternatives to fight these parasites. We therefore consider that determining the metabolic mechanisms involved in ivermectin resistance is of great relevance. The comparative proteomic analysis here reported shows the relevance of the active detoxifying metabolism in the midgut of resistant ticks, which may be key for the development of novel control methods.

Keywords: Ivermectin; Proteomics; Resistance; Rhipicephalus microplus.