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Carbon dioxide (CO2) present in exhaled air is the most important sensory cue for female blood-feeding mosquitoes, causing activation of long-distance host-seeking flight, navigation towards the vertebrate host1 and, in the case of Aedes aegypti, increased sensitivity to skin odours2. The CO2 detection machinery is therefore an ideal target to disrupt host seeking. Here we use electrophysiological assays to identify a volatile odorant that causes an unusual, ultra-prolonged activation of CO2-detecting neurons in three major disease-transmitting mosquitoes: Anopheles gambiae, Culex quinquefasciatus and A. aegypti. Importantly, ultra-prolonged activation of these neurons severely compromises their ability subsequently to detectCO2 for severalminutes. Wealso identify odours that strongly inhibit CO2-sensitive neurons as candidates for use in disruption of host-seeking behaviour, as well as an odour that evokes CO2-like activity and thus has potential use as a lure in trapping devices.Analysis of responses to panels of structurally related odours across the three mosquitoes and Drosophila, which have related CO2-receptor proteins, reveals a pattern of inhibition that is often conserved. We use video tracking in wind-tunnel experiments to demonstrate that the novel ultra-prolonged activators can completely disruptCO2-mediated activation as well as source-finding behaviour inAedes mosquitoes, even after the odour is no longer present. Lastly, semi-field studies demonstrate that use of ultra-prolonged activators disrupts CO2-mediated hut entry behaviour of Culex mosquitoes. The three classes of CO2-response-modifying odours offer powerful instruments for developing new generations of insect repellents and lures,which even insmall quantities can interfere with the ability of mosquitoes to seek humans.
Each year, A. gambiae,A. aegypti and C. quinquefasciatusmosquitoes transmit deadly diseases such asmalaria and dengue tomore than half a billion people and cause millions of deaths. Female mosquitoes need to find and obtain a bloodmeal froman infected person and subsequently find an uninfected human host to bite. Disruption of host-seeking in mosquitoes could therefore reduce incidence of both steps.
Femalemosquitoesdependprimarilyonolfactory cues that are emitted fromhuman breath, skin and sweat to find hosts3. Yet very fewstrategies that target the mosquito olfactory system, like the effective repellent N,N-diethyl-m-toluamide (DEET)4,5, have emerged. However, the relativelyhigh cost ofDEETand the need for repeated application to the skin at high concentrations (10-70%) precludes its use in tropical countries. DEET is also known tomelt plastics6, and to block cation channels4 and cholinesterase activity in mammals7. Moreover,...