Cellular and molecular basis of IR3535 perception in Drosophila

Background IR3535 is among the most widely used synthetic insect repellents, particularly for the mitigation of mosquito-borne diseases such as malaria, yellow fever, dengue, and Zika, as well as to control flies, ticks, fleas, lice, and mites. These insects are well-known vectors of deadly diseases that affect humans, livestock, and crops. Moreover, global warming could increase the populations of these vectors. Results Here, we performed IR3535 dose-response analyses on Drosophila melanogaster, a well-known insect model organism, using electrophysiology and binary food choice assays. Our findings indicated that bitter-sensing gustatory receptor neurons (GRNs) are indispensable to detect IR3535. Further, potential candidate gustatory receptors were screened, among which GR47a was identified as a key molecular sensor. 0.1%-0.4% ranges of IR3535 affected larval development and mortality. Additionally, DEET (i.e., another commonly used insecticide) was found to exert synergistic effects when co-administered with IR3535. Conclusion Our findings confirmed that IR3535 directly activates bitter-sensing GRNs, which are mediated by GR47a. This relatively safe and highly potent insecticide can be largely used in combination with DEET to increase its efficiency to protect livestock and crops. Collectively, our findings suggest that the molecular sensors elucidated herein could be used as targets for the development of alternative insecticides. This article is protected by copyright. All rights reserved.