Novel high-throughput screens of Anopheles gambiae odorant receptors reveal candidate behaviour-modifying chemicals for mosquitoes
AUTHORS
ABSTRACT
Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis, as well as numerous arboviral-associated illnesses, such as dengue and yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Anopheles gambiae Giles, the modulation of which is likely to provide opportunities for disease reduction. In this context, recent studies characterize a large divergent family of An. gambiae odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work facilitates high-throughput, cell-based calcium mobilization screens of AgOR-expressing human embryonic kidney cells identifying a large number of conventional AgOR ligands, as well as the first nonconventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.
Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis, as well as numerous arboviral-associated illnesses, such as dengue and yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Anopheles gambiae Giles, the modulation of which is likely to provide opportunities for disease reduction. In this context, recent studies characterize a large divergent family of An. gambiae odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work facilitates high-throughput, cell-based calcium mobilization screens of AgOR-expressing human embryonic kidney cells identifying a large number of conventional AgOR ligands, as well as the first nonconventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.