Commonly Used Insect Repellents Hide Human Odors from Anopheles Mosquitoes

Abstract

The mode of action for most mosquito repellents is unknown. This is primarily due to the difficulty in monitoring how the mosquito olfactory system responds to repellent odors. Here, we used the Q-system of binary expression to enable activity-dependent Ca 2+ imaging in olfactory neurons of the African malaria mosquito Anopheles coluzzii. This system allows neuronal responses to common insect repellents to be directly visualized in living mosquitoes from all olfactory organs, including the antenna. The synthetic repellents N,N-diethyl-meta-toluamide (DEET) and IR3535 did not activate Anopheles odorant receptor co-receptor (Orco)-expressing olfactory receptor neurons (ORNs) at any concentration, and picaridin weakly activated ORNs only at high concentrations. In contrast, natural repellents (i.e. lemongrass oil and eugenol) strongly activated small numbers of ORNs in the Anopheles mosquito antennae at low concentrations. We determined that DEET, IR3535, and picaridin decrease the response of Orco-expressing ORNs when these repellents are physically mixed with activating human-derived odorants. We present evidence that synthetic repellents may primarily exert their olfactory mode of action by decreasing the amount of volatile odorants reaching ORNs. These results suggest that synthetic repellents disruptively change the chemical profile of host scent signatures on the skin surface, rendering humans invisible to Anopheles mosquitoes.

Insect repellents mediate species-specific olfactory behaviours in mosquitoes

“…In this close proximity response assay ( Fig. 1b), DEET odours did not directly repel Anopheles mosquitoes [13]. This work raised several questions.…”

“…(2) DEET modulates chemoreceptor activity in response to attractive odorants ('scrambling') [10][11][12]; (3) DEET works directly on the odorants to decrease their volatility leading to a decreased amount of the odorants reaching the mosquitoes ('masking') [4,13]. In addition to its role in affecting mosquito olfaction, DEET also functions as a robust contact repellent in Aedes, which requires the tarsus to trigger avoidance [14].…”

“…1a), which is sufficient time for insect olfactory systems to evolve independently and respond differently to odorants, including repellents [18][19][20][21][22][23][24][25]. Therefore, the lack of agreement on how DEET and other mosquito repellents work from previous studies might reflect the assumption and use of a single mosquito species as representative for all mosquito species [4,[6][7][8][9][10][11]13]. In addition, to behaviourally test the effect of repellents on host seeking, previous studies typically used human odours as attractants and measured the change in attraction in the presence of the repellent [3,6,8,[26][27][28].…”

“…In addition, to behaviourally test the effect of repellents on host seeking, previous studies typically used human odours as attractants and measured the change in attraction in the presence of the repellent [3,6,8,[26][27][28]. In these assays, synthetic repellents interact with human odorants and decrease their volatility [4,13], leading to an indirect inhibition of chemoreceptor responses towards human odorants (chemical masking). A simple olfactory behavioural assay was recently developed to monitor the response of Anopheles mosquitoes towards repellent odours alone [13].…”

“…In these assays, synthetic repellents interact with human odorants and decrease their volatility [4,13], leading to an indirect inhibition of chemoreceptor responses towards human odorants (chemical masking). A simple olfactory behavioural assay was recently developed to monitor the response of Anopheles mosquitoes towards repellent odours alone [13]. In this close proximity response assay ( Fig.…”