Carboxylic acids that drive mosquito attraction to humans activate Ionotropic Receptors

Abstract

The mosquito,Aedes aegypti, is highly anthropophilic and continues to transmit debilitating arboviruses within human populations. Female mosquitoes are attracted to sources of blood by responding to odor plumes that are emitted by their preferred hosts. Acidic volatile compounds, including carboxylic acids, represent particularly salient odors driving this attraction. Importantly, carboxylic acids are major constituents of human sweat and volatiles generated by skin microbes. As such, they are likely to impact human host preference, which is a dominant factor in disease transmission cycles. A more complete understanding of mosquito host attraction will necessitate the elucidation of molecular mechanisms of volatile odor detection that function in peripheral sensory neurons. Recent studies have shown that members of the variant ionotropic glutamate receptor gene family are necessary for physiological and behavioral responses to acidic volatiles inAedes. In this study, we have identified a subfamily of variant ionotropic receptors that share sequence homology across several important vector species and are likely to be activated by carboxylic acids. Moreover, we demonstrate that selected members of this subfamily are activated by short chain carboxylic acids in a heterologous cell expression system. Our results are consistent with the hypothesis that members of this receptor class underlie acidic volatile sensitivity in vector mosquitoes and provide a frame of reference for future development of novel mosquito attractant and repellent technologies.

Heterologous expression of insect IRs in transgenicDrosophila melanogaster

“…The "ionotropic receptor decoder" system offers several advantages over the traditional ex vivo approach, such as heterologous expression in Xenopus oocytes, which has been used in a limited number of non-model species for IR deorphanization (Xu et al, 2014;Ray et al, 2023;Pitts et al, 2017;Shan et al, 2019;Hou et al, 2022). One of the main advantages of using an in vivo system like the "ionotropic receptor decoder" is that it closely mimics the native olfactory sensillum environment, ensuring a high-fidelity receptive field for the expressed receptor.…”

“…Several of these IR75 subunits have been functionally characterized, primarily showing tuning to carboxylic acids. For instance, AaegIR75k1 and AaegIR75k3 from Aedes aegypti, as well as AalbIR75e from Aedes albopictus, respond to C7-C9 carboxylic acids (Ray et al, 2023), and the agonist of A. gambiae AgIR75k are C6-C10 carboxylic acids (Pitts et al, 2017). Lepidopteran IRs AsegIR75p.1 and AsegIR75q.1 from Agrotis segetum also respond to medium-chain fatty acids, with hexanoic acid being the most potent agonist for AsegIR75p.1 (Huo et al, 2022).…”

“…The copyright holder for this preprint this version posted September 12, 2023. ; https://doi.org/10.1101/2023.09.12.557369 doi: bioRxiv preprint the role of IRs outside Drosophila. So far, the methods used include knock down and in situ recording of neuronal activity (Xu et al, 2014) or the heterologous expression in Xenopus laevis oocytes (Xu et al, 2014;Ray et al, 2023;Pitts et al, 2017;Shan et al 2019;Hou et al 2022). This is a commonly used heterologous expression system for the electrophysiological characterization of iGluRs and it has been the only method used for functional characterization of IRs from lineages outside Diptera species, specifically the lepidopteran Agrotis segetum (Hou et al, 2022) and the wasp Microplitis mediator (Shan et al;.…”