Journal Article

Mosquito odorant receptor for DEET and methyl jasmonate

Choo, Young-Moo, Xu, Pingxi, De La Rosa, Alyssa, Leal, Walter S.

2014

Overview

Insect repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET ( N , N -diethyl-3-methylbenzamide) is a 6-decade-old synthetic repellent, which is still considered the gold standard of mosquito repellents. Mosquitoes use their sense of smell to detect DEET, but there are currently two hypotheses regarding its mode of action: activation of ionotropic receptor IR40a vs. odorant receptor(s). Here, we demonstrate that DEET, picaridin, insect repellent 3535, and p-menthan-3,8-diol activate the odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus . Electrophysiological and behavioral assays showed that CquiIR40a knockdown had no significant effect on DEET detection and repellency. By contrast, reduction of CquiOR136 transcript levels led to a significant decrease in electroantennographic responses to DEET and a complete lack of repellency. Thus, direct activation of an odorant receptor, not an ionotropic receptor, is necessary for DEET reception and repellency in Culex mosquitoes. Interestingly, methyl jasmonate, a repellent derived from the nonvolatile jasmonic acid in the signaling pathway of plant defenses, elicited robust responses in CquiOR136•CquiOrco-expressing Xenopus oocytes, thus suggesting a possible link between natural products with long insect–plant evolutionary history and synthetic repellents. Significance DEET ( N , N -diethyl-3-methylbenzamide) has intrigued medical entomologists, neurobiologists, insect physiologists, and chemical ecologists for decades, and hitherto it was not known how and why it works. We have discovered an odorant receptor in the southern house mosquito, which is essential for repellency, thus unravelling how DEET works. Additionally, we have identified a link between this synthetic repellent and methyl jasmonate, thus suggesting that DEET might work by mimicking defensive compound(s) from plants. The discovery of a molecular target may pave the way for the development of better and more affordable insect repellents.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Acetates / Acetates - pharmacology / Aldehydes - pharmacology / Animals / Aquatic insects / Arthropod Antennae - physiology / Avoidance Learning / beta-Alanine - analogs & derivatives / beta-Alanine - pharmacology / Biological Sciences / Cloning, Molecular / Culex / Culex - drug effects / Culex - physiology / Culex quinquefasciatus / Cyclopentanes - pharmacology / deet / DEET - pharmacology / Double stranded RNA / ecologists / Electrophysiology / entomologists / Feeding Behavior - drug effects / Feeding Behavior - physiology / Female / Female animals / Flowers & plants / Heptanoic acids / Insect antennae / insect repellents / Insect Repellents - pharmacology / Insect vectors / insects / Malaria / Menthol - analogs & derivatives / Menthol - pharmacology / methyl jasmonate / Mode of action / Models, Neurological / Molecular Sequence Data / Mosquitoes / Mosquitos / Natural products / odor compounds / Odorant receptors / Oocytes / Oxylipins - pharmacology / Piperidines - pharmacology / Receptors / Receptors, Ionotropic Glutamate - genetics / Receptors, Ionotropic Glutamate - physiology / Receptors, Odorant - biosynthesis / Receptors, Odorant - drug effects / Receptors, Odorant - genetics / Receptors, Odorant - physiology / Recombinant Fusion Proteins - metabolism / Repellents / RNA Interference / Smell - genetics / Smell - physiology / Transcription, Genetic / Vector-borne diseases / Xenopus / Xenopus laevis