Bohbot, J. D. | Search bioRxiv

bioRxiv2020

Mosquito indolergic receptors belong to an ancient and functionally conserved Dipteran gene lineage

Diptera is a megadiverse group of flies with sophisticated chemical detection systems, which exploits an incredible variety of ecological niches. Among the vast array of odorants in natural environments, indoles stand out as playing crucial roles in mediating fly behavior. In mosquitoes, indolic compounds are detected by an ancient class of conserved indolergic Odorant Receptors (indolORs). In this study, we have identified a set of 92 putative indolOR genes encoded in the genomes of Nematoceran and Brachyceran flies, resolved their phylogenetic relationships, and defined conserved elements in their gene structures. Further, we have quantified indolOR transcript abundance in the antennae of the housefly, Musca domestica, and have characterized MdomOR30a as a skatole receptor using a heterologous expression system. The presence of indolORs in species operating in different ecological contexts suggests that indoles act as pleiotropic signals for resource exploitation at multiple developmental stages. Further characterization of indolORs will impact our understanding of insect chemical ecology and will provide targets for the development of novel odor-based tools that can be integrated into existing vector surveillance and control programs.

evolutionary biology↗

bioRxiv2020

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

Odorant-dependent behaviors in insects are triggered by the binding of odorant ligands to the variable subunits of heteromeric olfactory receptors. Previous studies have shown, however, that specific odor binding to ORco, the common subunit of odorant receptor heteromers, may alter allosterically olfactory receptor function and affect profoundly subsequent behavioral responses. Here we report on the identification of several antagonists of the odorant receptor co-receptor of the African malaria vector Anopheles gambiae, AgamORco, in a small collection of natural volatile organic compounds (VOCs) using a relevant insect cell-based screening platform. Because some of the identified antagonists were previously shown to strongly repel Anopheles and Culex mosquitoes, here we examined the bioactivities of the identified antagonists against Aedes, the third major genus of the Culicidae family. The tested antagonists were found to inhibit the function of Ae. aegypti ORco ex vivo and repel Asian tiger, Ae. albopictus, adult mosquitoes. Specific antagonist binary mixtures elicited higher repellency than single antagonists. Binding competition assays suggested antagonist binding to distinct ORco sites as a likely cause for the enhanced repellence of the blends. These findings demonstrate that a simple screening assay may be used for the identification of allosteric modifiers of olfactory-driven behaviors capable of providing enhanced indoor and outdoor protection against multiple mosquito borne infectious diseases.

neuroscience↗