Summary
DEET (N,N -diethyl-meta-toluamide) is the most effective and broadly used insect repellent, but its mechanism of action is both complex and controversial [1]. Previous work demonstrated that DEET acts both on insect smell [2][3][4][5][6] and taste [7][8][9][10][11] systems. Its olfactory mode of action requires the odorant co-receptor orco [2,3,6], while its gustatory repellency is mediated by activation of bitter taste receptors and neurons in the proboscis upon ingestion [8]. Together, these data have led to the assumption that DEET acts only on olfactory and gustatory pathways. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but are rapidly repelled after contacting DEET-treated skin [6]. To understand the basis of this contact chemorepellency, we carried out a series of behavioral experiments and discovered that DEET acts in three distinct ways: through smell, taste, and contact. DEET and bitter tastants are feeding deterrents when ingested, but only DEET is capable of mediating contact repellency on human skin. We show that the repellent touch of DEET is mediated by the tarsal segments of the legs, and not gustatory neurons in the proboscis as previously believed. This work establishes mosquito leg appendages as the actual sensors of DEET, and highlights the existence of an unknown sensory pathway that is independent of bitter taste. These results will inform the search for novel contact-based insect repellents.
KeywordsDEET; insect repellent; mosquito; Aedes aegypti; bitter; ingestion; contact chemorepellency; taste; touch; smell
Highlights• DEET and bitters are both repellent when ingested by Aedes aegypti female mosquitoes • Only DEET is additionally repellent upon contact • Repellency of DEET on skin is mediated solely by the legs • Any of the three pairs of legs can sense DEET and prevent mosquitoes from biting . CC-BY 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. To study contact repellency, we used heteroallelic orco 5/16 mutant mosquitoes throughout this study to eliminate the olfactory effects of DEET. Here we define "olfactory" repellency" as avoidance of volatile DEET that is dependent on orco, "taste" and "gustatory repellency" as the anti-feedant effect seen after ingesting fluid, and "contact repellency" as the repellency of a surface, usually but not exclusively human skin.Both D. melanogaster flies [8] and Ae. aegypti mosquitoes [12] will reject sucrose tainted with bitter substances. Previous work in D. melanogaster flies [8] demonstrated that DEET acts as a bitter tastant when ingested, and that bitter-sensitive taste neurons and gustatory receptor genes required to sense bitters are responsible. Similar bitter-and DEET-sensitive neurons were identified on the proboscis of the mosquito [10] but their influence on behavior is unknown. To ask if DEET can inhibit Ae. aegypt...