Targeting a Dual Detector of Skin and CO2 to Modify Mosquito Host Seeking

• Mosquito CO2 neurons (cpA) detect human skin odor and are important for attraction
• In silico screen of >440k chemicals finds excellent agonists and antagonists of cpA
• Blocking cpA activity abolishes attraction behavior toward human skin odor and CO2
• Agonists that lure mosquitoes to traps represent safe affordable control

SummaryFemale mosquitoes that transmit deadly diseases locate human hosts by detecting exhaled CO2 and skin odor. The identities of olfactory neurons and receptors required for attraction to skin odor remain a mystery. Here, we show that the CO2-sensitive olfactory neuron is also a sensitive detector of human skin odorants in both Aedes aegypti and Anopheles gambiae. We demonstrate that activity of this neuron is important for attraction to skin odor, establishing it as a key target for intervention. We screen ∼0.5 million compounds in silico and identify several CO2 receptor ligands, including an antagonist that reduces attraction to skin and an agonist that lures mosquitoes to traps as effectively as CO2. Analysis of the CO2 receptor ligand space provides a foundation for understanding mosquito host-seeking behavior and identifies odors that are potentially safe, pleasant, and affordable for use in a new generation of mosquito control strategies worldwide.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (4111 K)

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