Functional characterization of mosquito host-seeking and oviposition repellents

Mosquitoes are vectors for many deadly diseases, including malaria which kills more than 400,000 people around the world every year. Mosquitoes primarily depend on their sense of smell (olfaction), in combination with other senses, to find hosts for blood-feeding and select their egg laying habitats. Therefore, olfactory cues such as repellents can be used to control mosquitoes and their disease. We used a combination of behavioral, imaging, and electrophysiology methods to investigate the mode of action of currently used repellents in the malaria mosquito Anopheles coluzzii. We found that natural repellents such as lemongrass oil and p-menthane-3,8-diol (PMD) strongly activate small numbers of olfactory receptor neurons (ORNs) in the Anopheles mosquito antennae. In contrast, synthetic repellents such as DEET and IR3535 do not activate Anopheles ORNs but rather reduce the volatility of human skin odorants leading to a decreased olfactory response towards these odorants. This suggests that synthetic repellents “mask” skin odorants and render humans invisible to Anopheles mosquitoes. To test our findings behaviorally, we developed a behavioral assay in which repellents can be tested directly, independent from human odors. We found that natural repellents, but not synthetic repellents, directly repel Anopheles mosquitoes. Overall, these findings will help guide decisions on choosing the right repellent for each mosquito species, and will help develop safer alternatives to currently used mosquito repellents.