| Title: | Volatile allosteric antagonists of mosquito odorant receptors inhibit human-host attraction |
| Author(s): | Kythreoti G; Sdralia N; Tsitoura P; Papachristos DP; Michaelakis A; Karras V; Ruel DM; Yakir E; Bohbot JD; Schulz S; Iatrou K; |
| Address: | "Institute of Biosciences and Applications, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi, Greece. Entomology and Agricultural Zoology, Benaki Phytopathological Institute, Kifissia, Greece. Department of Entomology, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel. Institute of Organic Chemistry, Technische Universitat Braunschweig, Braunschweig, Germany. Institute of Biosciences and Applications, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi, Greece. Electronic address: iatrou@bio.demokritos.gr" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "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 allosterically alter olfactory receptor function and profoundly affect subsequent behavioral responses. Using an insect cell-based screening platform, we identified and characterized several antagonists of the odorant receptor coreceptor of the African malaria vector Anopheles gambiae (AgamORco) in a small collection of natural volatile organic compounds. Because some of the identified antagonists were previously shown to strongly repel Anopheles and Culex mosquitoes, we examined the bioactivities of the identified antagonists against Aedes, the third major genus of the Culicidae family. The tested antagonists inhibited the function of Ae. aegypti ORco ex vivo and repelled adult Asian tiger mosquitoes (Ae. albopictus). Binary mixtures of specific antagonists elicited higher repellency than single antagonists, and binding competition assays suggested that this enhanced repellence is due to antagonist interaction with distinct ORco sites. Our results also suggest that the enhanced mosquito repellency by antagonist mixtures is due to additive rather than synergistic effects of the specific antagonist combinations on ORco function. Taken together, these findings provide novel insights concerning the molecular aspects of odorant receptor function. Moreover, our results demonstrate that a simple screening assay may be used for the identification of allosteric modifiers of olfactory-driven behaviors capable of providing enhanced personal protection against multiple mosquito-borne infectious diseases" |
| Keywords: | "Aedes/*drug effects/physiology Aldehydes/chemistry/pharmacology Animals Anopheles/*drug effects/physiology Bicyclic Monoterpenes/chemistry/pharmacology Binding, Competitive Cinnamates/chemistry/pharmacology Cymenes/chemistry/pharmacology DEET/chemistry/ph;" |
| Notes: | "MedlineKythreoti, Georgia Sdralia, Nadia Tsitoura, Panagiota Papachristos, Dimitrios P Michaelakis, Antonios Karras, Vasileios Ruel, David M Yakir, Esther Bohbot, Jonathan D Schulz, Stefan Iatrou, Kostas eng Research Support, Non-U.S. Gov't 2020/12/11 J Biol Chem. 2021 Jan-Jun; 296:100172. doi: 10.1074/jbc.RA120.016557. Epub 2020 Dec 18" |
