Cell‐Based Screening Platforms for Identification of Modifiers of Odor‐Triggered Mosquito Behaviors Acting through Binding to the ORco Subunit of Odorant Receptor Heteromers
Authors: Iatrou Kostas , Tsitoura Panagiota , Sdralia Nadia , Konstantopoulou Maria 
Published: June 2021

Insect olfactory receptors (ORs) are heteromeric ion channels consisting of a common subunit, ORco, and one of many variable subunits, ORx, to which odorants, receptor agonists or antagonists, bind in an ORx‐specific manner. In cells expressing the ORco subunit alone, however, ORco may also form a functional channel that is activated by ORco‐specific agonists. We have previously shown that mosquito repellents that block odor‐specific responses of multiple ORs of Anopheles gambiae mosquitoes, act as ORco antagonists that are capable of suppressing its activation by ORco‐specific agonists. We have also shown that the in vitro responses of heteromeric receptors that are induced by ORx‐specific agonists are enhanced by one to two orders of magnitude in the presence of either of two ORco‐specific agonists, VUAA1 and OrcoRAM2. The latter finding suggests the induction of allosteric changes in ORx‐bound heteromeric receptor complexes, which are caused by the binding of the ORco agonist and result in enhanced ion influx into the receptor‐expressing cells. To expand on these findings, we have designed a lepidopteran insect cell‐based expression platform that allows the fast screening of collections of pure compounds and compound mixtures for the presence of A. gambiae ORco agonists and antagonists in a single screening assay. Because mosquitoes should be able to detect the presence of olfaction‐relevant bioactive molecules in their natural environments, we screened for the presence of relevant compounds in (i) collections of essential oils obtained from aromatic plants and fractions thereof, which contain volatile constituents, and (ii) collections of pure volatiles of plant or bacterial origin. The initial screening effort resulted in the identification of a small number of hits acting as ORco‐specific agonists or antagonists from both types of examined collections. These hits are currently examined further to establish their functional relevance and effectiveness against mosquito populations in vivo. Should this testing prove the validity of the hypothesis that newly‐identified volatile ORco ligands may modify olfaction‐based mosquito behaviors in a predicted fashion, additional capacities will be generated for enhanced personal protection against indoor and outdoor transmission of malaria and other mosquito‐borne infectious diseases. We also note that equivalent screening platforms could be designed for identification of behavior modifiers of the same type for other arthropod species of interest.

Support or Funding Information

This work has been supported by the ENAROMaTIC consortium project (grant No FP7‐222927 of the EC) and was carried out in the facilities of the OPENSCREEN‐GR National (Greece) Research Infrastructure.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.