The Effects of Chemical Repellents on Olfactory Receptors of the Aedes aegypti Mosquito in Response to Human Odorants – the Mechanism Underlying Host-seeking and Blood-feeding Behaviors

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Project Summary/Abstract The long-term goal of the proposed research is to develop effective, alternative chemical repellents that counter mosquito host-seeking and blood-feeding behaviors by disrupting the mosquito’s human odor- detection mechanism. The information gained in this proposal will inform the development of chemical repellents that by-pass known mechanisms of insecticide resistance in order to reduce the incidence of mosquito-borne diseases and to protect public health. When seeking blood meals, mosquitoes rely on their olfactory system to detect chemical odorants emitted by their human hosts [8]; these human odorants assist in the t ransmission of mosquito-related diseases to humans. Using chemical repellents that disrupt the odor-detection mechanisms in mosquitoes may be a viable alternative strategy to current insecticides, such as DEET (Section A.3), for desensitizing the mosquito’s ability to smell humans. A better understanding is needed of the mechanisms governing the interactions among chemical repellents, host odorants, and the response of olfactory receptors of mosquitoes to enable the development of new repellent alternatives that will desensitize the mosquito to humans, thus interfering with the mosquito recognizing its human host. In preliminary studies, we investigated the interactions of 48 repellent chemicals with the olfactory receptor neurons (ORNs) of the Aedes aegypti mosquito, and identified several terpene/terpenoid compounds that exhibit inhibitory effects on mosquito ORNs [40]. We have further characterized the responses of the ORN to 103 compounds and discovered that certain human odorants elicit decreased responses after blood feeding, suggesting these human odorants are involved in Aedes aegypti host-seeking behaviors [21]. We hypothesize that chemical repellents exhibiting inhibitory effects (inhibitory chemical repellents) may interact with human odorants, resulting in the disruption of the mosqutoes’ olfactory recognition of human hosts and in diminished responses to them when mosquitoes are seeking feeding hosts. The proposed research objective is to determine the chemical repellents that affect a mosquito’s olfactory sense in order to prevent it from finding a human target or host. The proposed aims are to: 1) characterize the responses of Ae. aegypti ORs to inhibitory chemical repellents and to human odorants that may be involved in Ae. aegypti host-seeking and blood-feeding and 2) determine the competition effects of inhibitory chemical repellents and human odorants on Ae. aegypti ORs.