An odorant receptor from Anopheles gambiae that demonstrates enantioselectivity to the plant volatile, linalool

Autoři: Robert Mark Huff aff001;  R. Jason Pitts aff001
Působiště autorů: Department of Biology, Baylor University, Waco, Texas, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225637


Insects express chemical receptors within sensory neurons that are activated by specific cues in the environment, thereby influencing the acquisition of critical resources. A significant gap in our current understanding of insect chemical ecology is defining the molecular mechanisms that underlie sensitivity to plant-emitted volatiles. Linalool is a commonly-occurring monoterpene that has various effects on insect behavior, either acting as an attractant or a repellent, and existing in nature as one of two possible stereoisomers, (R)-(–)-linalool and (S)-(+)-linalool. In this study, we have used a cell-based functional assay to identify linalool and structurally-related compounds as ligands of Odorant receptor 29, a labellum-expressed receptor in the malaria vector mosquito, Anopheles gambiae (AgamOr29). While (R)-(–)-linalool activates AgamOr29, a mixture of the (R) and (S) stereoisomers activates the receptor with higher potency, implying enantiomeric selectivity. Orthologs of Or29 are present in the genomes of Anophelines within the Cellia subgenus. The conservation of this receptor across Anopheline lineages suggests that this ecologically important compound might serve as an attraction cue for nectar-seeking mosquitoes. Moreover, the characterization of a mosquito terpene receptor could serve as a foundation for future ligand-receptor studies of plant volatiles and for the discovery of compounds that can be integrated into push-pull vector control strategies.

Klíčová slova:

Insects – Introns – Mosquitoes – Odorants – Sensory receptors – Xenopus oocytes – Olfactory receptor neurons – Anopheles gambiae


1. Zwiebel LJ, Takken W. Olfactory regulation of mosquito-host interactions. Insect Biochem Mol Biol. 2004; 34: 645–52. doi: 10.1016/j.ibmb.2004.03.017 15242705

2. Takken W. The Role of Olfaction in Host-Seeking of Mosquitos—a Review. Int J Trop Insect Sci. 1991; 12: 287–295.

3. Clements AN, Clements AN. The biology of mosquitoes. New York: Chapman & Hall; 1992.

4. Carey AF, Wang G, Su CY, Zwiebel LJ, Carlson JR. Odorant reception in the malaria mosquito Anopheles gambiae. Nature 2010; 464: 66–71. doi: 10.1038/nature08834 20130575

5. Otienoburu PE, Ebrahimi B, Phelan PL, Foster WA. Analysis and optimization of a synthetic milkweed floral attractant for mosquitoes. J Chem Ecol. 2012; 38: 873–881. doi: 10.1007/s10886-012-0150-6 22711028

6. Chaiphongpachara T, Padidpoo O, Chansukh KK, Sumruayphol S. Efficacies of five edible mushroom extracts as odor baits for resting boxes to attract mosquito vectors: A field study in Samut Songkhram Province, Thailand. Trop Biomed. 2018; 35: 653–663.

7. Su E, Bohbot JD, Zwiebel LJ. Peripheral olfactory signaling in insects. Curr Opin Insect Sci. 2014; 6: 86–92. doi: 10.1016/j.cois.2014.10.006 25584200

8. Freeman EG, Wisotsky Z, Dahanukar A. Detection of sweet tastants by a conserved group of insect gustatory receptors. Proc Natl Acad Sci USA 2014; 111: 1598–1603. doi: 10.1073/pnas.1311724111 24474785

9. Benton R, Vannice K, Gomezdiaz C, Vosshall L. Variant Ionotropic Glutamate Receptors as Chemosensory Receptors in Drosophila. Cell 2009; 136: 149–162. doi: 10.1016/j.cell.2008.12.001 19135896

10. Takken W, Knols BGJ. Odor-mediated behavior of afrotropical malaria mosquitoes. Annu. Rev. Entomol. 1999; 44: 131–157. doi: 10.1146/annurev.ento.44.1.131 9990718

11. McBride CS, Baier F, Omondi AB, Spitzer SA, Lutomiah J, Sang R, et al. Evolution of mosquito preference for humans linked to an odorant receptor. Nature 2014; 515: 222–227. doi: 10.1038/nature13964 25391959

12. Bernier UR, Kline DL, Barnard DR, Schreck CE, Yost RA. Analysis of human skin emanations by gas chromatography/mass spectrometry. 2. Identification of volatile compounds that are candidate attractants for the yellow fever mosquito (Aedes aegypti). Anal Chem. 2000; 72: 747–756. doi: 10.1021/ac990963k 10701259

13. Allan SA, Bernier UR, Kline DL. Evaluation of oviposition substrates and organic infusions on collection of Culex in Florida. J Am Mosq Control Assoc. 2005; 21: 268–273. doi: 10.2987/8756-971X(2005)21[268:EOOSAO]2.0.CO;2 16252516

14. Foster WA, Hancock RG. Nectar-related olfactory and visual attractants for mosquitoes. J Am Mosq Control Assoc. 1994; 10: 288–296. 8965081

15. Riffell JA. The Neuroecology of a Pollinator’s Buffet: Olfactory Preferences and Learning in Insect Pollinators. Integr Comp Biol. 2011; 51: 781–793. doi: 10.1093/icb/icr094 21803792

16. Chen Z, Kearney CM. Nectar protein content and attractiveness to Aedes aegypti and Culex pipiens in plants with nectar/insect associations. Acta Tropica 2015; 146: 81–88. doi: 10.1016/j.actatropica.2015.03.010 25792420

17. Pichersky E, Lewinsohn E, Croteau R. Purification and characterization of S-Linalool Synthase, an enzyme involved in the production of floral scent in Clarkia breweri. Arch Biochem Biophys. 1995; 316: 803–807. doi: 10.1006/abbi.1995.1107 7864636

18. Pichersky E, Gershenzon J. The formation and function of plant volatiles: perfumes for pollinator attraction and defense. Curr Opin Plant Biol. 2002; 5: 237–243 doi: 10.1016/s1369-5266(02)00251-0 11960742

19. Jonsson M, Anderson P. Electrophysiological response to herbivore-induced host plant volatiles in the moth Spodoptera littoralis. Physiol Entomol. 1999; 24: 377–385.

20. Malo EA, Castrejon-Gomez VR, Cruz-Lopez L, Rojas JC. Antennal sensilla and electrophysiological response of male and female Spodoptera frugiperda (Lepidoptera: Noctuidae) to conspecific sex pheromone and plant odors. Ann Entomol Soc Am. 2004; 97: 1273–1284.

21. Røstelien T, Stranden M, Borg-Karlson AK, Mustaparta H. Olfactory receptor neurons in two heliothine moth species responding selectively to aliphatic green leaf volatiles, aromatic compounds, monoterpenes and sesquiterpenes of plant origin. Chem Senses 2005; 30: 443–461. doi: 10.1093/chemse/bji039 15917371

22. Ulland S, Ian E, Borg-Karlson AK, Mustaparta H. Discrimination between Enantiomers of Linalool by Olfactory Receptor Neurons in the Cabbage Moth Mamestra brassicae (L.). Chem Senses 2006; 31: 25–34.

23. Reisenman CE, Riffell JA, Bernays EA, Hildebrand JG. Antagonistic effects of floral scent in an insect-plant interaction. Proceedings of the Royal Society B 2010; 277: 2371–2379. doi: 10.1098/rspb.2010.0163 20335210

24. Kline DL, Bernier UR, Posey KH, Barnard DR. Olfactometric evaluation of spatial repellents for Aedes aegypti, J Med Entomol. 2003; 40: 463. doi: 10.1603/0022-2585-40.4.463 14680112

25. Yu BT, Ding YM, Mo JC. Behavioural response of female Culex pipiens pallens to common host plant volatiles and synthetic blends. Parasit Vectors 2015; 8: 598. doi: 10.1186/s13071-015-1212-8 26577584

26. Bohbot JD, Dickens JC. Characterization of an enantioselective odorant receptor in the yellow fever mosquito Aedes aegypti. PLoS One 2009; 4: e7032. doi: 10.1371/journal.pone.0007032 19753115

27. Dekel A, Pitts RJ, Bohbot JD. Evolutionarily conserved odorant receptor function questions ecological context of octenol role in mosquitoes. Sci Rep. 2016; 6: 37330. doi: 10.1038/srep37330 27849027

28. Sugawara Y, Hara C, Aoki T, Sugimoto N, Masujima T. Odor Distinctiveness between Enantiomers of Linalool: Difference in Perception and Responses Elicited by Sensory Test and Forehead Surface Potential Wave Measurement. Chem Senses 2000; 25, 77–84. doi: 10.1093/chemse/25.1.77 10667997

29. Koulivand PH, Khaleghi Ghadiri M, Gorji A. Lavender and the nervous system. Evid Based Complement Alternat Med. 2013; 2013: 6811304.

30. Pajaro-Castro N, Caballero-Gallardo K, Olivero-Verbel J. Neurotoxic Effects of Linalool and β-Pinene on Tribolium castaneum Herbst. Molecules 2017; 22: 2052.

31. Gaire S, Scharf ME, Gondhalekar AD. Toxicity and neurophysiological impact of plant essential oil components on bed bugs (Cimicidae: Hemiptera). Sci Rep. 2019; 9: 3961. doi: 10.1038/s41598-019-40275-5 30850655

32. Re L, Barocci S, Sonnino S, Mencarelli A, Vivani C, Paolucci G, et al. Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol Res. 2000; 42: 177–182. doi: 10.1006/phrs.2000.0671 10887049

33. Jun HJ, Lee JH, Kim J, Jia Y, Kim KH, Hwang KY, et al. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014; 55: 1098–1110. doi: 10.1194/jlr.M045807 24752549

34. Jarvis GE, Barbosa R, Thompson AJ. Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling. J Pharmacol Exp Ther. 2016: 356; 549–562. doi: 10.1124/jpet.115.230011 26669427

35. Milanos S, Elsharif SA, Janzen D, Buettner A, Villman C. Metabolic Products of Linalool and Modulation of GABAA Receptors. Front Chem. 2017; 5: 46. doi: 10.3389/fchem.2017.00046 28680877

36. López V, Nielsen B, Solas M, Ramírez MJ, Jäger AK. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets. Front Pharmacol. 2017; 8: 280. doi: 10.3389/fphar.2017.00280 28579958

37. Neafsey DE, Waterhouse RM, Abai MR, Aganezov SS, Alekseyev MA, Allen JE, et al. Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes. Science 2015; 347: 1258522. doi: 10.1126/science.1258522 25554792

38. Pitts RJ, Rinker DC, Jones PL, Rokas A, Zwiebel LJ. Transcriptome profiling of chemosensory appendages in the malaria vector Anopheles gambiae reveals tissue- and sex-specific signatures of odor coding. BMC Genomics 2011; 12: 271. doi: 10.1186/1471-2164-12-271 21619637

39. Rinker DC, Zhou X, Pitts RJ, The AGC Consortium, Rokas A, Zwiebel LJ. Antennal transcriptome profiles of anopheline mosquitoes reveal human host olfactory specialization in Anopheles gambiae. BMC Genomics 2013; 14: 749. doi: 10.1186/1471-2164-14-749 24182346

40. Saveer AM, Pitts RJ, Ferguson ST, Zwiebel LJ. Characterization of Chemosensory Responses on the Labellum of the Malaria Vector Mosquito, Anopheles coluzzii. Sci Rep. 2018; 8: 5656. doi: 10.1038/s41598-018-23987-y 29618749

41. Harbach RE. The phylogeny and classification of Anopheles. Manguin S.(Ed.), Anopheles Mosquitoes–New Insights into Malaria Vectors, InTech Open Access 2013:3–55.

42. Norris LC, Norris DE. Phylogeny of anopheline (Diptera: Culicidae) species in southern Africa, based on nuclear and mitochondrial genes. J Vector Ecol. 2015; 40: 16–27. doi: 10.1111/jvec.12128 26047180

43. Hill CA, Fox AN, Pitts RJ, Kent LB, Tan PL, Chrystal MA, et al. G Protein-Coupled Receptors in Anopheles gambiae. Science 2002; 298: 176–178. doi: 10.1126/science.1076196 12364795

44. Carroll MJ, Schmelz EA, Meagher RL, Teal PE. Attraction of Spodoptera frugiperda Larvae to Volatiles from Herbivore-Damaged Maize Seedlings. J Chem Ecol. 2006; 32: 1911–1924. doi: 10.1007/s10886-006-9117-9 16902828

45. Lutz EK, Lahondere C, Vinauger C, Riffell JA. Olfactory learning and chemical ecology of olfaction in disease vector mosquitoes: A life history perspective. Curr Opin Insect Sci. 2017; 20: 75–83. doi: 10.1016/j.cois.2017.03.002 28602240

46. Gouagna LC, Poueme RS, Dabiré KR, Ouédraogo JB, Fontenille D, Simard F. Patterns of sugar feeding and host plant preferences in adult males of An. gambiae (Diptera: Culicidae) J Vector Ecol. 2010; 35: 267–276. doi: 10.1111/j.1948-7134.2010.00082.x 21175931

47. Nyasembe VO, Teal PE, Mukabana WR, Tumlinson JH, Torto B. Behavioural response of the malaria vector Anopheles gambiae to host plant volatiles and synthetic blends. Parasit Vectors 2012; 5: 1. doi: 10.1186/1756-3305-5-1 22212459

48. Omondi AB, Ghaninia M, Dawit M, Svensson T, Ignell R. Age-dependent regulation of host seeking in Anopheles coluzzii. Sci Rep. 2019; 9: 9699. doi: 10.1038/s41598-019-46220-w 31273284

49. Bedoukian RH. Method and Compositions for Inhibiting the Scent Tracking Ability of Mosquitoes and Biting Midges, Washington D.C.: U.S. Patent and Trademark Office, 2005. Published U.S. Patent Application No. 20050090563.

50. Nikbakhtzadeh MR, Terbot JW, Otienoburu PE, Foster WA. Olfactory basis of floral preference of the malaria vector Anopheles gambiae (Diptera: Culicidae) among common African plants. J Vector Ecol. 2014; 39: 372–383. doi: 10.1111/jvec.12113 25424267

51. Gillij YG, Gleiser RM, Zygadlo JA. Mosquito repellent activity of essential oils of aromatic plants growing in Argentina. Bioresour Technol. 2008; 99: 2507–15. doi: 10.1016/j.biortech.2007.04.066 17583499

52. Degenhardt J, Gershenzon J, Baldwin IT, Kessler A. Attracting friends to feast on foes: engineering terpene emission to make crop plants more attractive to herbivore enemies. Curr Opin in Biotechnol. 2003;14: 169–176.

53. Muller GC, Junnila A, Kravchenko VD, Revay EE, Butler J, Schlein Y. Indoor Protection against mosquito and sand fly bites: a comparison between citronella, linalool, and geraniol candles. J Am Mosq Control Assoc. 2008;24: 150–153. doi: 10.2987/8756-971X(2008)24[150:IPAMAS]2.0.CO;2 18437831

54. Langenheim JH. Higher plant terpenoids: A phytocentric overview of their ecological roles. J Chem Ecol. 1994;20: 1223–1280. doi: 10.1007/BF02059809 24242340

55. Byers JA. Attraction of bark beetles, Tomicus piniperda, Hylurgops palliates, and Trypodendron domesticum and other insects to short-chain alcohols and monoterpenes. J Chem Ecol. 1992;18: 2385–2402. doi: 10.1007/BF00984957 24254878

56. Phillips MA, Croteau RB. Resin-based defenses in conifers. Trends Plant Sci. 1999:4; 184–190. doi: 10.1016/s1360-1385(99)01401-6 10322558

57. Benelli G, Beier JC. Current vector control challenges in the fight against malaria. Acta Trop. 2017 Oct;174: 91–96. doi: 10.1016/j.actatropica.2017.06.028 28684267

58. Takken W. Push-pull strategies for vector control. Malar J. 2010; 9(Suppl 2): I16.

59. Obermayr U, Ruther J, Bernier UR, Rose A, Geier M. Evaluation of a Push-Pull Approach for Aedes aegypti (L.) Using a Novel Dispensing System for Spatial Repellents in the Laboratory and in a Semi-Field Environment. PLoS One 2015;10: e0134063. doi: 10.1371/journal.pone.0134063 26207826

60. Menger DJ, Omusula P, Holdinga M, Homan T, Carreira AS, Vandendaele P, et al. Field Evaluation of a Push-Pull System to Reduce Malaria Transmission. PLoS One 2015;10: e0123415. doi: 10.1371/journal.pone.0123415 25923114

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