Characterisation of thymol effects on RDL receptors from the bee parasite Varroa destructor

A major contributor to bee colony decline is infestation with its most devastating pest, the mite Varroa destructor. To control these mites, thymol is often used, although how it achieves this is not understood. One well-documented action of thymol is to modulate GABA-activated ion channels, which includes insect RDL receptors, a known insecticidal target. Here we have cloned two Varroa RDL subunits, one of which is similar to the canonical RDL subunit, while the other has some differences in M4, and, to a lesser extent, M2 and its binding site loops. Expression of this unusual RDL receptor in Xenopus oocytes reveals GABA-activated receptors, with an EC₅₀ of 56 microM. In contrast to canonical RDL receptors, thymol does not enhance GABA-elicited responses in this receptor, and concentration response curves reveal a decrease in GABA I_max in its presence; this decrease is not seen when similar data are obtained from Apis RDL receptors. We conclude that an M2 T6'M substitution is primarily responsible for the different thymol effects, and suggest that understanding how and where thymol acts could assist in the design of novel bee-friendly miticides.