The ovipositor cue indole inhibits animal host attraction in Aedes aegypti (Diptera: Culicidae) mosquitoes.
(R)-1-octen-3-ol
Aedes aegypti
DEET
IR3535
Indole
OR8
Repellent
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
12 Nov 2022
12 Nov 2022
Historique:
received:
17
07
2022
accepted:
07
10
2022
entrez:
11
11
2022
pubmed:
12
11
2022
medline:
16
11
2022
Statut:
epublish
Résumé
Mosquitoes are responsible for disease transmission worldwide. They possess the ability to discriminate between different ecological resources, including nectar sources, animal hosts and oviposition sites, a feature mediated by their olfactory system. Insect repellents, such as N,N-diethyl-meta-toluamide (also called DEET), have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents currently available for personal protection against mosquitoes are topically applied to the skin and operate at a short range. In our search for potential long-range inhibitors of attractants to human hosts, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former with the ability to block odorant receptor function and inhibit human host attraction in a similar way as DEET. We used the two-electrode voltage clamp system to assay Xenopus laevis oocytes as a platform to compare the pharmacological effect of commercially available insect repellents and indole on the Aedes aegypti (R)-1-octen-3-ol receptor, OR8, a receptor involved in the decision-making of female mosquitoes to identify human hosts. We also conducted arm-in-a-cage and wind-tunnel bioassays to explore the effect of indole on human host-seeking female Aedes aegypti mosquitoes. Our results demonstrate that indole inhibited the Aedes aegypti (R)-1-octen-3-ol receptor OR8. In our arm-in-a-cage assay, 1 M of DEET reduced mosquito visits on average by 69.3% while the same indole concentration achieved 97.8% inhibition. This effect of indole on flight visits was dose-dependent and disappeared at 1 μM. In the flight tunnel, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to the control. Indole significantly inhibits OR8 activation by (R)-1-octen-3-ol, mosquito visits to a human hand and long-range human host-seeking. The volatility of indole may be leveraged to develop a novel insect repellent in the context of personal mosquito protection.
Sections du résumé
BACKGROUND
BACKGROUND
Mosquitoes are responsible for disease transmission worldwide. They possess the ability to discriminate between different ecological resources, including nectar sources, animal hosts and oviposition sites, a feature mediated by their olfactory system. Insect repellents, such as N,N-diethyl-meta-toluamide (also called DEET), have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents currently available for personal protection against mosquitoes are topically applied to the skin and operate at a short range. In our search for potential long-range inhibitors of attractants to human hosts, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former with the ability to block odorant receptor function and inhibit human host attraction in a similar way as DEET.
METHODS
METHODS
We used the two-electrode voltage clamp system to assay Xenopus laevis oocytes as a platform to compare the pharmacological effect of commercially available insect repellents and indole on the Aedes aegypti (R)-1-octen-3-ol receptor, OR8, a receptor involved in the decision-making of female mosquitoes to identify human hosts. We also conducted arm-in-a-cage and wind-tunnel bioassays to explore the effect of indole on human host-seeking female Aedes aegypti mosquitoes.
RESULTS
RESULTS
Our results demonstrate that indole inhibited the Aedes aegypti (R)-1-octen-3-ol receptor OR8. In our arm-in-a-cage assay, 1 M of DEET reduced mosquito visits on average by 69.3% while the same indole concentration achieved 97.8% inhibition. This effect of indole on flight visits was dose-dependent and disappeared at 1 μM. In the flight tunnel, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to the control.
CONCLUSIONS
CONCLUSIONS
Indole significantly inhibits OR8 activation by (R)-1-octen-3-ol, mosquito visits to a human hand and long-range human host-seeking. The volatility of indole may be leveraged to develop a novel insect repellent in the context of personal mosquito protection.
Identifiants
pubmed: 36369215
doi: 10.1186/s13071-022-05545-8
pii: 10.1186/s13071-022-05545-8
pmc: PMC9652956
doi:
Substances chimiques
1-octen-3-ol
WXB511GE38
DEET
134-62-3
Indoles
0
Insect Repellents
0
Receptors, Odorant
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
422Subventions
Organisme : Israel Science Foundation
ID : 719/21
Informations de copyright
© 2022. The Author(s).
Références
Schreck CE, Gilbert IH, Weidhaas DE, Posey KH. Spatial action of mosquito repellents. J Econ Entomol. 1970;63:1576–8.
pubmed: 5483821
doi: 10.1093/jee/63.5.1576
Khan AA, Maibach HI. A study of insect repellents. 1. Effect on the flight and approach by Aedes aegypti. J Econ Entomol. 1972;65:1318–21.
pubmed: 5085790
doi: 10.1093/jee/65.5.1318
Mayer MS, James JD. Attraction of Aedes aegypti (L.): responses to human arms, carbon dioxide, and air currents in a new type of olfactometer. Bull Entomol Res. 1969;58:629–42.
doi: 10.1017/S0007485300057357
Hao H, Wei J, Dai J, Du J. Host-seeking and blood-feeding behavior of Aedes albopictus (Diptera: Culicidae) exposed to vapors of geraniol, citral, citronellal, eugenol, or anisaldehyde. J Med Entomol. 2008;45:533–9.
pubmed: 18533449
doi: 10.1093/jmedent/45.3.533
Bohbot JD, Dickens JC. Insect repellents: modulators of mosquito odorant receptor activity. PLoS ONE. 2010;5:e12138. https://doi.org/10.1371/journal.pone.0012138 .
doi: 10.1371/journal.pone.0012138
pubmed: 20725637
pmcid: 2920324
Bohbot JD, Fu L, Le TC, Chauhan KR, Cantrell CL, Dickens JC. Multiple activities of insect repellents on odorant receptors in mosquitoes. Med Vet Entomol. 2011;25:436–44.
pubmed: 21395633
doi: 10.1111/j.1365-2915.2011.00949.x
Bohbot JD, Dickens JC. Odorant receptor modulation: ternary paradigm for mode of action of insect repellents. Neuropharmacology. 2012;62:2086–95.
pubmed: 22269900
doi: 10.1016/j.neuropharm.2012.01.004
Syed Z, Leal W. Mosquitoes smell and avoid the insect repellent DEET. Proc Natl Acad Sci USA 2008;36:13598–603. http://www.pnas.org/cgi/content/abstract/105/36/13598 .
Afify A, Betz JF, Riabinina O, Lahondère C, Potter CJ. Commonly used insect repellents hide human odors from Anopheles mosquitoes. Curr Biol. 2019;29(21):3669-3680.e5. https://doi.org/10.1016/j.cub.2019.09.007 .
Afify A, Potter CJ. Insect repellents mediate species-specific olfactory behaviours in mosquitoes. Malar J. 2020;19:127.
pubmed: 32228701
pmcid: 7106743
doi: 10.1186/s12936-020-03206-8
Bohbot J, Pitts RJ, Kwon HW, Rutzler M, Robertson HM, Zwiebel LJ. Molecular characterization of the Aedes aegypti odorant receptor gene family. Insect Mol Biol. 2007;16:525–37.
pubmed: 17635615
pmcid: 3100214
Lu T, Qiu YT, Wang G, Kwon JY, Rutzler M, Kwon H-W, et al. Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae. Curr Biol. 2007;17:1533–44.
pubmed: 17764944
pmcid: 3113458
doi: 10.1016/j.cub.2007.07.062
Bohbot JD, Dickens JC. Characterization of an enantioselective odorant receptor in the yellow fever mosquito Aedes aegypti. PLoS ONE. 2009;4:e7032.
pubmed: 19753115
pmcid: 2737144
doi: 10.1371/journal.pone.0007032
Dekel A, Pitts RJ, Yakir E, Bohbot JD. Evolutionarily conserved odorant receptor function questions ecological context of octenol role in mosquitoes. Sci Rep. 2016;6:37330.
pubmed: 27849027
pmcid: 5110965
doi: 10.1038/srep37330
Gibson G, Torr S. Visual and olfactory responses of haematophagous Diptera to host stimuli. Med Vet Entomol. 1999;13:2–23.
pubmed: 10194745
doi: 10.1046/j.1365-2915.1999.00163.x
Takken W. The role of olfaction in host-seeking of mosquitoes: a review. Int J Trop Insect Sci. 1991;12:287–95.
doi: 10.1017/S1742758400020816
Takken W, Knols BG. Odor-mediated behavior of Afrotropical malaria mosquitoes. Annu Rev Entomol. 1999;44:131–57.
pubmed: 9990718
doi: 10.1146/annurev.ento.44.1.131
Lindh JM, Borg-Karlson A-K, Faye I. Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (Diptera: Culicidae) and oviposition response to bacteria-containing water. Acta Trop. 2008;107:242–50.
pubmed: 18671931
doi: 10.1016/j.actatropica.2008.06.008
Allan SA, Kline DL. Evaluation of organic infusions and synthetic compounds mediating oviposition in Aedes albopictus and Aedes aegypti (Diptera: Culicidae). J Chem Ecol. 1995;21:1847–60.
pubmed: 24233834
doi: 10.1007/BF02033681
Du Y, Millar J. Electroantennogram and oviposition bioassay responses of Culex quinquefasciatus and Culex tarsalis (Diptera: Culicidae) to chemicals in odors from Bermuda grass infusions. J Med Entomol. 1999;36:158–66.
pubmed: 10083752
doi: 10.1093/jmedent/36.2.158
Collins L, Blackwell A. Olfactory cues for oviposition behavior in Toxorhynchites moctezuma and Toxorhynchites amboinensis (Diptera: Culicidae). J Med Entomol. 2002;39:121–6.
pubmed: 11931244
doi: 10.1603/0022-2585-39.1.121
Millar JG, Chaney JD, Beehler JW, Mulla MS. Interaction of the Culex quinquefasciatus egg raft pheromone with a natural chemical associated with oviposition sites. J Am Mosq Control Assoc. 1994;10:374–9.
pubmed: 7807079
Takken W, Loon JJA, Adam W. Effects of gonotrophic development of Anopheles gambiae (Diptera: Culicidae) on physiological and behavioural responses to human odour. J Insect Physiol. 2001;47:303–10.
pubmed: 11119776
doi: 10.1016/S0022-1910(00)00107-4
R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2021.
Xu P, Zeng F, Bedoukian RH, Leal WS. DEET and other repellents are inhibitors of mosquito odorant receptors for oviposition attractants. Insect Biochem Mol Biol. 2019;113:103224.
pubmed: 31446031
pmcid: 6752049
doi: 10.1016/j.ibmb.2019.103224
Xu P, Choo Y-M, Chen Z, Zeng F, Tan K, Chen T-Y, et al. Odorant inhibition in mosquito olfaction. iScience. 2019;19:25–38.
pubmed: 31349189
pmcid: 6660600
doi: 10.1016/j.isci.2019.07.008
Ditzen M, Pellegrino M, Vosshall LB. Insect odorant receptors are molecular targets of the insect repellent DEET. Science. 2008;319:1838–42.
pubmed: 18339904
doi: 10.1126/science.1153121
Pellegrino M, Steinbach N, Stensmyr MC, Hansson BS, Vosshall LB. A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor. Nature. 2011;478:511–4.
pubmed: 21937991
pmcid: 3203342
doi: 10.1038/nature10438
Sanford JL, Shields VDC, Dickens JC. Gustatory receptor neuron responds to DEET and other insect repellents in the yellow-fever mosquito Aedes aegypti. Naturwissenschaften. 2013;100:269–73.
pubmed: 23407786
doi: 10.1007/s00114-013-1021-x
Dennis EJ, Goldman OV, Vosshall LB. Aedes aegypti mosquitoes use their legs to sense DEET on contact. Curr Biol. 2019;29:1551-1556.e5.
pubmed: 31031114
pmcid: 6504582
doi: 10.1016/j.cub.2019.04.004
Grant GG, Estrera RR, Pathak N, Hall CD, Tsikolia M, Linthicum KJ, et al. Interactions of DEET and novel repellents with mosquito odorant receptors. J Med Entomol. 2020;57:1032–40.
pubmed: 32048720
doi: 10.1093/jme/tjaa010
Elgaali H, Hamilton-Kemp TR, Newman MC, Collins RW, Yu K, Archbold DD. Comparison of long-chain alcohols and other volatile compounds emitted from food-borne and related Gram positive and Gram negative bacteria. J Basic Microbiol. 2002;42:373–80.
pubmed: 12442299
doi: 10.1002/1521-4028(200212)42:6<373::AID-JOBM373>3.0.CO;2-4
Chen G, Zhang R-R, Liu Y, Sun W-B. Spore dispersal of fetid by feces of mycophagous insects. J Chem Ecol. 2014;40:893–9.
pubmed: 25064696
doi: 10.1007/s10886-014-0481-6
Turlings TC, Tumlinson JH, Heath RR, Proveaux AT, Doolittle RE. Isolation and identification of allelochemicals that attract the larval parasitoid, Cotesia marginiventris (Cresson), to the microhabitat of one of its hosts. J Chem Ecol. 1991;17:2235–51.
pubmed: 24258602
doi: 10.1007/BF00988004
Meijerink J, Braks MAH, Brack AA, Adam W, Dekker T, Posthumus MA, et al. Identification of olfactory stimulants for Anopheles gambiae from human sweat samples. J Chem Ecol. 2000;26:1367–82.
doi: 10.1023/A:1005475422978
Blackwell A, Johnson S. Electrophysiological investigation of larval water and potential oviposition chemo-attractants for Anopheles gambiae s.s. Ann Trop Med Parasitol. 2000;94:389–98.
pubmed: 10945049
doi: 10.1080/00034983.2000.11813554
Cork A. Olfactory basis of host location by mosquitoes and other Haematophagous Diptera. In: Bock GR, Cardew G, editors. Olfaction in mosquito-host interactions Ciba foundation symposium 200. Chichester: Wiley and Sons; 1996. p. 71–88.
Millar JG, Chaney JD, Mulla MS. Identification of oviposition attractants for Culex quinquefasciatus from fermented Bermuda grass infusions. J Am Mosq Control Assoc. 1992;8:11–7.
pubmed: 1583482
Blackwell A, Mordue A, Hansson B. A behavioural and electrophysiological study of oviposition cues for Culex quinquefasciatus. Physiol Entomol. 1993;18:343–8.
doi: 10.1111/j.1365-3032.1993.tb00607.x
Beehler J, Millar J, Mulla M. Synergism between chemical attractants and visual cues influencing oviposition of the mosquito, Culex quinquefasciatus (Diptera: Culicidae). J Chem Ecol. 1993;19:635–44.
pubmed: 24249007
doi: 10.1007/BF00984998
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;72:747–56.
pubmed: 10701259
doi: 10.1021/ac990963k
US Environmental Protection Agency (USEP). Indole PC Code 025000. Washington DC: US Environmental Protection Agency; 2009. https://nepis.epa.gov/Exe/ZyPDF.cgi/P1004V9K.PDF?Dockey=P1004V9K.PDF . Accessed 3 Nov 2022.
Smyth HF Jr, Carpenter CP, Well CS, Pozzani UC, Striegel JA. Range-finding toxicity data: list VI. Am Ind Hyg Assoc J. 1962;23:95–107.
pubmed: 13914538
doi: 10.1080/00028896209343211
Verhulst NO, Weldegergis BT, Menger D, Takken W. Attractiveness of volatiles from different body parts to the malaria mosquito Anopheles coluzzii is affected by deodorant compounds. Sci Rep. 2016;6:27141.
pubmed: 27251017
pmcid: 4890431
doi: 10.1038/srep27141
Zeng F, Xu P, Tan K, Zarbin PHG, Leal WS. Methyl dihydrojasmonate and lilial are the constituents with an “off-label” insect repellence in perfumes. PLoS ONE. 2018;13:e0199386.
pubmed: 29920544
pmcid: 6007898
doi: 10.1371/journal.pone.0199386