The molecular basis of fatty acid taste in Aedes aegypti

Abstract Mosquito bites are not simply an itchy annoyance- diseases spread through mosquito bites are a leading cause of morbidity and mortality each year and impose a heavy economic burden on healthcare systems around the world. When an insect disease vector lands on a host, it uses contact chemosensation, or taste, to inform its decision to bite and thereby spread disease. Insect repellants that function to disrupt sensation of taste cues, including DEET, have proven effective as antifeedants but are not without significant limitations. Many biting insects, including the dengue vector Aedes (Ae.)aegypti, show a greater reduction in biting and blood feeding when presented with fatty acids (FAs), the palatable component of dietary fats, than with DEET. In spite of findings like this, the receptor mechanisms employed in mosquito taste, including FA taste, are largely unknown and remain unexplored. Many taste modalities have been studied extensively in Drosophila melanogaster, which is a dipteran relative of Ae. aegypti, yet the molecular requirements for FA taste are unresolved. To this effect, we propose to employ our recent findings in the powerful model organism Drosophila to identify the currently unknown cellular and receptor mechanisms underlying FA taste in Ae. aegypti. In Drosophila, low concentrations of FAs are attractive, while high concentrations are aversive. In addition to recent evidence that gustatory attraction to low concentrations of FAs is conferred by a specific subset of gustatory receptor neurons (GRNs) and requires phospholipase C, data from our lab suggest requirements for a G-protein coupled receptor (GPCR) and a TRP channel. In addition to its role in attraction, the TRP channel is also required for aversion. Our preliminary results show for the first time that Ae. aegypti displays bimodal attraction and aversion to FAs. In addition, Ae. aegypti encodes homologs for the candidate FA receptors identified in Drosophila. The aims of this proposal will build on preliminary findings in Ae. aegypti. The goal of Aim #1 is to identify the range of relevant FA concentrations that impact biting and blood feeding in Ae. aegypti and define the role of taste in controlling the bimodal FA responses. In Aim #2 we will test the taste requirement for an Ae. aegypti TRP channel homolog and candidate GPCRs in attraction and aversion towards FAs. By identifying the receptor mechanisms for FA detection, this proposal offers to not only improve our understanding of a poorly defined insect taste modality but also to identify specific targets for improved insect repellants.