Commonly used insect repellents hide human odors from Anopheles mosquitoes

Abstract

18The mode of action for most mosquito repellents is unknown. This is primarily due to the 19 difficulty in monitoring how the mosquito olfactory system responds to repellent odors. 20Here, we used the Q-system of binary expression to enable activity-dependent Ca 2+ 21 imaging in olfactory neurons of the African malaria mosquito Anopheles coluzzii. This 22 disruptively change the chemical profile of host scent signatures on the skin surface 34 rendering humans invisible to mosquitoes. 35 36 Introduction 37Mosquitoes are vectors for many debilitating diseases such as malaria, Zika, dengue 38 fever, and yellow fever. Malaria alone caused an estimated 435000 deaths in 2017 1 . 39Mosquitoes primarily depend on olfaction, in combination with other senses, to locate 40 their hosts 2,3 . Therefore, targeting the mosquito's sense of smell using repellent 41 odorants is an effective strategy to prevent them from biting humans. The synthetic 42 compound N,N-diethyl-meta-toluamide (DEET) is the most widely used mosquito 43 repellent in public use since 1957 4,5 . However, DEET has some drawbacks, including 44 high concentrations (~>30%) are required for it to be effective, an unpleasant odor and 45 oily feeling to some people, and the ability to dissolve some plastics and synthetic 46 rubber 4 . Commercially synthetized alternatives to DEET have been developed (IR3535, 47 picaridin), but these too have similar drawbacks, such as also requiring high 48 concentrations to be effective. In order to improve or identify new repellents, a better 49 understanding of how insect repellents affect a mosquito's olfactory system is needed. 50 However, the olfactory mode of action of synthetic insect repellents such as DEET, 51 IR3535, and picaridin, as well as natural insect repellents such as lemongrass oil and 52 eugenol, is surprisingly not well understood. 53The olfactory system of the Anopheles gambiae species of mosquitoes consists 54 of three organs: the antennae, maxillary palps, and labella 2,6,7 . Each of these organs is 55 covered with sensory hairs called sensilla, and each sensillum houses olfactory sensory 56 neurons that may contain one of three types of chemoreceptors: odorant receptors 57 (ORs), gustatory receptors (Grs), and/or ionotropic receptors (IRs). ORs are expressed 58 in the majority of olfactory neurons, and each OR is expressed along with the Odorant 59Receptor Co-receptor (Orco) to form a receptor complex that is either narrowly or 60 broadly tuned to a variety of host-derived odors 2,6,8 . Grs, specifically Gr22, Gr23, and 61Gr24, are expressed in sensilla on the mosquito maxillary palps and respond to carbon 62 dioxide 9 . IRs are likely activated by acids and amines 10,11 . 63A consensus for how DEET affects the mosquito olfactory system and alters host 64 seeking behavior has not yet emerged. Currently, there are three hypotheses of how 65 DEET affects mosquitoes: 1) DEET directly activates chemoreceptors (ORs, Grs, and/or 66 IRs) on the mosquito antennae, maxillary palps, or the labella to drive repe...

The ion channel ppk301 controls freshwater egg-laying in the mosquito Aedes aegypti

“…To build a flexible system for expressing a diverse array of effector transgenes, we employed the Q-binary expression system for transgene amplification (Potter et al, 2010), which has been successfully implemented in An. gambiae malaria mosquitoes (Riabinina et al, 2016; Afify et al, 2019). We used CRISPR-Cas9 with the same guide RNA used to generate the ppk301 mutant to introduce an in-frame T2A sequence into the ppk301 locus followed by the QF2 transcriptional activator (Figure 4B).…”

Contact repellency by l‐menthol is mediated by TRPM channels in the red flour beetle Tribolium castaneum

“…DEET has some drawbacks; for example, it needs to be used in high concentrations (up to 30%) for biting arthropods, which dissolves some plastics; it is oily and has an unpleasant smell; and there is the possibility of developing DEET‐insensitive mutants, such as in Drosophila melanogaster (Meigen) 12,13 . To improve and discover new repellents, some repellents, such as IR3535, pidaridin, and even natural botanical‐based insect repellents, have been studied, but the mode of action remains unclear 14 …”

Volatile allosteric antagonists of mosquito odorant receptors inhibit normal odor-dependent behaviors

“…Proof of this hypothesis will have to await the identification of the specific antagonist binding sites and detailed mutagenesis studies. The proposed mode of action for the identified bioactive VOCs is thus distinct from the receptorindependent function of DEET, which, apparently, "repels" mosquitoes and other insects, at least in part, via its association with volatile receptor ligands acting as attractants, thereby reducing their volatility and effective concentrations thus masking their presence in the mosquito's environment (51).…”