The parasitic interaction honeybee-Varroa: A model for new acaricidal target discovery – ParaGluRsite

Ectoparasitic diseases, caused by parasites like ticks, lice, fleas, and mites, present growing challenges in treatment. Current medications rely on a limited set of molecules, leading to resistance in parasite populations and environmental repercussions. Finding environmentally sustainable therapeutic alternatives is necessary.

Our project aims to validate ionotropic glutamate receptors (iGluRs) as new molecular targets for developing ectoparasiticides. These receptors are central to neuromuscular transmission in arthropods, including mites and insects.

The varroa mite (Varroa destructor) is a significant ectoparasite of bees implicated in the decline of bee colonies. By focusing on the bee-varroa parasite model, where both host and parasite belong to the same arthropod phylum, we are imposing high specificity in the search for new molecular targets and theirs associated compounds. These must exhibit potent activity against mites while sparing insects. This strategy means that biodiversity conservation is taken into account at a very early stage in the search for new acaracides.

From an experimental point of view, our inclusion of Ixodes ricinus, the prevalent mite in Europe and a vector of Lyme disease, along with the aphid, a notorious insect pest in legume crops, broadens the scope of our work. This expansion enhances our likelihood of yielding results and potential treatments that could benefit multiple parasites.

A comparative genome analysis of insects, including bees and aphids, alongside mites like Varroa and Ixodes ricinus, reveals molecular diversity in ionotropic glutamate receptors (iGluRs). This discovery opening the way (1) to differential screening of biolomolecules to identify specific modulators of mite iGluRs, and (2) to the design of dsRNAs specific to these iGluRs. The biomolecules examined will be compounds extracted from essential oils, and peptides derived from spider and ant venoms whose binding to iGluRs will be optimised in silico, and whose delivery efficiency will be enhanced by various nanovectorisation approaches.

The safety of molecules capable of inhibiting the locomotion of Varroa mites or Ixodes ticks will be evaluated through locomotor and cognitive behavioral tests on bees, in vivo toxicological tests on aphids, and finally on synaptic transmission in rodents.