# Gustatory avoidance of fatty acids by Aedes aegypti depends on an arthropod-specific TRP channel

## TL;DR

This study shows that Aedes aegypti mosquitoes avoid fatty acids using a specific TRP channel, which could help in developing new mosquito repellents.

## Contribution

The study identifies the TRP channel Painless1 as a key sensor for fatty acid taste in Aedes aegypti and Drosophila.

## Key findings

- Painless1 is required for fatty acid avoidance in Aedes aegypti and action potentials in gustatory receptor neurons.
- In Drosophila, Painless supports both attraction to low and aversion to high fatty acid doses via different neurons.
- Painless homologs are arthropod-specific, making them a promising target for selective mosquito repellents.

## Abstract

The mosquito, Aedes aegypti, transmits the viruses afflicting millions of people with dengue and other diseases. Fatty acids (FAs) on skin can deter blood feeding. However, the sensors required for FA taste in mosquitoes are unknown. We identify the transient receptor potential channel Painless (Pain) as essential for FA taste in two dipterans. In Drosophila, Painless supports attraction to low doses and aversion to high doses of FAs via distinct gustatory receptor neurons (GRNs). In Ae. aegypti, the Pain1 ortholog is required for FA avoidance, which suppresses the decision to blood feed or nectar feed, and for FA-induced action potentials in GRNs. Because Pain homologs are arthropod-restricted, they offer a promising selective target for next-generation repellents.

Mosquito-disease vectors, such as Aedes aegypti, use their sense of taste before deciding whether to consume a blood meal, or fly away. However, the molecular mechanisms controlling gustatory decisions in mosquitoes are largely unknown. The transient receptor potential (TRP) channel, Painless1 (Pain1), is an intriguing candidate for participating in Ae. aegypti taste since pain1 transcripts are detected in gustatory receptor neurons (GRNs). The Drosophila homolog, painless (pain) is also expressed in GRNs, where it is required for sensing allyl-isothiocyanate. Here, to identify additional gustatory roles for pain homologs, we first focused on Drosophila pain, which is widely expressed in multiple GRN classes. We demonstrated that pain mutations eliminated gustatory attraction to low fatty acids levels, repulsion to high levels, and fatty acid-induced action potentials. The attraction and repulsion depended on pain expression in different GRN classes. In contrast to Drosophila, when Aedes contacts fatty acids, they induce gustatory rejection only. Aedes pain1 is expressed in taste organs, and is required for gustatory avoidance of fatty acids, and for fatty acid-induced action potentials. Given that Pain homologs are found in insects but not vertebrates, Pain1 represents an intriguing target for developing repellents to diminish biting, and transmission of infectious agents by mosquito disease vectors.