Aedes aegypti Mosquitoes Use Their Legs to Sense DEET on Contact

DEET (N, N-diethyl-meta-toluamide) is the most effective and widely used insect repellent, but its mechanism of action is both complex and controversial [1]. DEET acts on insect smell [2–6] and taste [7–11], and its olfactory mode of action requires the odorant co-receptor orco [2, 3, 6]. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but they are rapidly repelled after contacting DEET-treated skin [6]. DEET inhibits food ingestion by Drosophila melanogaster flies, and this repellency is mediated by bitter taste neurons in the proboscis [9]. Similar neurons were identified in the mosquito proboscis, leading to the hypothesis that DEET repels on contact by activating an aversive bitter taste pathway [10]. To understand the basis of DEET contact chemorepellency, we carried out behavioral experiments and discovered that DEET acts by three distinct mechanisms: smell, ingestion, and contact. Like bitter tastants, DEET is a feeding deterrent when ingested, but its bitterness per se does not fully explain DEET contact chemorepellency. Mosquitoes blood fed on human arms treated with high concentrations of bitters, but rapidly avoided DEET-treated skin and did not blood feed. Insects detect tastants both through their proboscis and legs. We show that DEET contact chemorepellency is mediated exclusively by the tarsal segments of the legs and not the proboscis. This work establishes mosquito legs as the behaviorally relevant contact sensors of DEET. These results will inform the search for molecular mechanisms mediating DEET contact chemorepellency and novel contact-based insect repellents. [Display omitted] •DEET and bitters inhibit Aedes aegypti female mosquito sugar ingestion•Only DEET completely prevents blood feeding on contact•Repellency of DEET on skin contact is mediated by the tarsal segments of the legs•Any pair of legs can sense DEET to prevent mosquito biting Dennis et al. show that while mosquitoes find DEET and bitters equally distasteful to ingest, only DEET repels mosquitoes on contact. This chemorepellency is mediated by the legs and not the proboscis. These results highlight the multi-modal repellency of DEET and may inform the design of new insect repellents that work on contact.