Exploring the molecular basis of insecticide resistance in the dengue vector Aedes aegypti: a case study in Martinique Island (French West Indies)
Tóm tắt
The yellow fever mosquito Aedes aegypti is a major vector of dengue and hemorrhagic fevers, causing up to 100 million dengue infections every year. As there is still no medicine and efficient vaccine available, vector control largely based on insecticide treatments remains the only method to reduce dengue virus transmission. Unfortunately, vector control programs are facing operational challenges with mosquitoes becoming resistant to commonly used insecticides. Resistance of Ae. aegypti to chemical insecticides has been reported worldwide and the underlying molecular mechanisms, including the identification of enzymes involved in insecticide detoxification are not completely understood. The present paper investigates the molecular basis of insecticide resistance in a population of Ae. aegypti collected in Martinique (French West Indies). Bioassays with insecticides on adults and larvae revealed high levels of resistance to organophosphate and pyrethroid insecticides. Molecular screening for common insecticide target-site mutations showed a high frequency (71%) of the sodium channel 'knock down resistance' (kdr) mutation. Exposing mosquitoes to detoxification enzymes inhibitors prior to bioassays induced a significant increased susceptibility of mosquitoes to insecticides, revealing the presence of metabolic-based resistance mechanisms. This trend was biochemically confirmed by significant elevated activities of cytochrome P450 monooxygenases, glutathione S-transferases and carboxylesterases at both larval and adult stages. Utilization of the microarray Aedes Detox Chip containing probes for all members of detoxification and other insecticide resistance-related enzymes revealed the significant constitutive over-transcription of multiple detoxification genes at both larval and adult stages. The over-transcription of detoxification genes in the resistant strain was confirmed by using real-time quantitative RT-PCR. These results suggest that the high level of insecticide resistance found in Ae. aegypti mosquitoes from Martinique island is the consequence of both target-site and metabolic based resistance mechanisms. Insecticide resistance levels and associated mechanisms are discussed in relation with the environmental context of Martinique Island. These finding have important implications for dengue vector control in Martinique and emphasizes the need to develop new tools and strategies for maintaining an effective control of Aedes mosquito populations worldwide.
Tài liệu tham khảo
WHO: Report of the Scientific Working Group on dengue. 2006, Document WHO/TDR/SWG/08 Geneva, Switzerland, World Health Organization
Yaicharoen R, Kiatfuengfoo R, Chaeronviriyaphap T, Rongnoparut P: Characterization of deltamethrin, resistance in field populations of Aedes aegypti in Thailand. J Vect Ecol. 2005, 30 (1): 144-150.
Ponlawat A, Scott JG, Harrington LC: Insecticide susceptibility of Aedes aegypti and Aedes albopictus across Thailand. J Med Entomol. 2005, 42 (5): 821-825. 10.1603/0022-2585(2005)042[0821:ISOAAA]2.0.CO;2.
Jirakanjanakit N, Rongnoparut P, Saengtharatip S, Chareonviriyaphap T, Duchn S, Bellec C, Yoksan S: Insecticide susceptible/resistance status in Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus (Diptera: Culicidae) in Thailand during 2003-2005. J Econ Entomol. 2007, 100 (2): 545-550. 10.1603/0022-0493(2007)100[545:IRSIAS]2.0.CO;2.
Jirakanjanakit N, Saengtharatip S, Rongnoparut P, Duchon S, Bellec C, Yoksan S: Trend of Temephos resistance in Aedes (Stegomyia) mosquitoes in Thailand during 2003-2005. Environ Entomol. 2007, 36 (3): 506-511. 10.1603/0046-225X(2007)36[506:TOTRIA]2.0.CO;2.
Rodriguez MM, Bisset JA, De Armas Y, Ramos F: Pyrethroid insecticide-resistant strain of Aedes aegypti from Cuba induced by deltamethrin selection. J Am Mosq Control Assoc. 2005, 21 (4): 437-445. 10.2987/8756-971X(2006)21[437:PISOAA]2.0.CO;2.
Rawlins SC, Martinez R, Wiltshire S, Legall G: A comparison of surveillance systems for the dengue vector Aedes aegypti in Port of Spain, Trinidad. J Am Mosq Control Assoc. 1998, 14 (2): 131-136.
Hemingway J, Hawkes NJ, McCarroll L, Ranson H: The molecular basis of insecticide resistance in mosquitoes. Insect Biochem Mol Biol. 2004, 34 (7): 653-665. 10.1016/j.ibmb.2004.03.018.
Hemingway J, Field L, Vontas J: An overview of insecticide resistance. Science. 2002, 298 (5591): 96-97. 10.1126/science.1078052.
Feyereisen R: Insect cytochrome P450. Comprehensive Molecular Insect Science. Edited by: Gilbert LI, Iatrou K, Gill S. 2005, Elsevier; Oxford, 1-77.
Ranson H, Hemingway J: Mosquito glutathione transferases. Methods Enzymol. 2005, 401: 226-241. 10.1016/S0076-6879(05)01014-1.
Hemingway J, Karunaratne SH: Mosquito carboxylesterases: a review of the molecular biology and biochemistry of a major insecticide resistance mechanism. Med Vet Entomol. 1998, 12 (1): 1-12. 10.1046/j.1365-2915.1998.00082.x.
Despres L, David JP, Gallet C: The evolutionary ecology of insect resistance to plant chemicals. Trends Ecol Evol. 2007, 22 (6): 298-307. 10.1016/j.tree.2007.02.010.
Poupardin R, Reynaud S, Strode C, Ranson H, Vontas J, David JP: Cross-induction of detoxification genes by environmental xenobiotics and insecticides in the mosquito Aedes aegypti: Impact on larval tolerance to chemical insecticides. InsectBiochem Mol Biol. 2008, 38 (5): 540-551. 10.1016/j.ibmb.2008.01.004.
Riaz MA, Poupardin R, Reynaud S, Strode C, Ranson H, David JP: Impact of glyphosate and benzo[a]pyrene on the tolerance of mosquito larvae to chemical insecticides. Role of detoxification genes in response to xenobiotics. Aquat Toxicol. 2009, 93 (1): 61-69. 10.1016/j.aquatox.2009.03.005.
Djouaka RF, Bakare AA, Bankole HS, Doannio JMC, Coulibaly ON, Kossou H, Tamo M, Basene HI, Popoola OK, Akogbeto MC: Does the spillage of petroleum products in Anopheles breeding sites have an impact on the pyrethroid resistance?. Malar J. 2007, 6: 159-10.1186/1475-2875-6-159.
Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, et al: The genome sequence of the malaria mosquito Anopheles gambiae. Science. 2002, 298 (5591): 129-149. 10.1126/science.1076181.
Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi ZY, Megy K, Grabherr M, et al: Genome sequence of Aedes aegypti, a major arbovirus vector. Science. 2007, 316 (5832): 1718-1723. 10.1126/science.1138878.
David JP, Strode C, Vontas J, Nikou D, Vaughan A, Pignatelli PM, Louis C, Hemingway J, Ranson H: The Anopheles gambiae detoxification chip: A highly specific microarray to study metabolic-based insecticide resistance in malaria vectors. Proc Natl Acad Sci USA. 2005, 102: 4080-4084. 10.1073/pnas.0409348102.
Strode C, Wondji CS, David JP, Hawkes NJ, Lumjuan N, Nelson DR, Drane DR, Karunaratne S, Hemingway J, Black WC, et al: Genomic analysis of detoxification genes in the mosquito Aedes aegypti. Insect Biochem Mol Biol. 2008, 38 (1): 113-123. 10.1016/j.ibmb.2007.09.007.
Muller P, Donnelly MJ, Ranson H: Transcription profiling of a recently colonised pyrethroid resistant Anopheles gambiae strain from Ghana. BMC Genomics. 2007, 8: 36-10.1186/1471-2164-8-36.
Muller P, Warr E, Stevenson BJ, Pignatelli PM, Morgan JC, Steven A, Yawson AE, Mitchell SN, Ranson H, Hemingway J: Field-caught permethrin-resistant Anopheles gambiae overexpress CYP6P3, a P450 that metabolises pyrethroids. Plos Genetics. 2008, 4 (11): 10.1371/journal.pgen.1000286.
Vontas J, Blass C, Koutsos AC, David JP, Kafatos FC, Louis C, Hemingway J, Christophides GK, Ranson H: Gene expression in insecticide resistant and susceptible Anopheles gambiae strains constitutively or after insecticide exposure. Insect Mol Biol. 2005, 14 (5): 509-521. 10.1111/j.1365-2583.2005.00582.x.
Vontas J, David JP, Nikou D, Hemingway J, Christophides GK, Louis C, Ranson H: Transcriptional analysis of insecticide resistance in Anopheles stephens i using cross-species microarray hybridization. Insect Mol Biol. 2007, 16 (3): 315-324. 10.1111/j.1365-2583.2007.00728.x.
Rodriguez MM, Bisset J, De Fernandez DM, Lauzan L, Soca A: Detection of insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Cuba and Venezuela. J Med Entomol. 2001, 38 (5): 623-628.
Rodriguez MM, Bisset J, Ruiz M, Soca A: Cross-resistance to pyrethroid and organophosphorus insecticides induced by selection with temephos in Aedes aegypti (Diptera: Culicidae) from Cuba. J Med Entomol. 2002, 39 (6): 882-888.
Brengues C, Hawkes NJ, Chandre F, McCarroll L, Duchon S, Guillet P, Manguin S, Morgan JC, Hemingway J: Pyrethroid and DDT cross-resistance in Aedes aegypti is correlated with novel mutations in the voltage-gated sodium channel gene. Med Vet Entomol. 2003, 17 (1): 87-94. 10.1046/j.1365-2915.2003.00412.x.
Macoris MD, Andrighetti MTM, Takaku L, Glasser CM, Garbeloto VC, Bracco JE: Resistance of Aedes aegypti from the State of Sao Paulo, Brazil, to organophosphates insecticides. Memorias Do Instituto Oswaldo Cruz. 2003, 98 (5): 703-708.
Saavedra-Rodriguez K, Urdaneta-Marquez L, Rajatileka S, Moulton M, Flores AE, Fernandez-Salas I, Bisset J, Rodriguez M, McCall PJ, Donnelly MJ, et al: A mutation in the voltage-gated sodium channel gene associated with pyrethroid resistance in Latin American Aedes aegypti. Insect Mol Biol. 2007, 16 (6): 785-798.
Marcombe S, Carron A, Darriet F, Etienne M, Agnew P, Tolosa M, Yp-Tcha MM, Lagneau C, Yébakima A, Corbel V: Reduced Efficacy of Pyrethroid Space Sprays for Dengue Control in an Area of Martinique with Pyrethroid Resistance. Am J Tropical Med Hyg. 2009, 80 (5): 745-751.
Wirth MC, Georghiou GP: Selection and characterization of temephos resistance in a population of Aedes Aegypti from Tortola. British Virgin Islands. J Am Mosq Control Assoc. 1999, 15 (3): 315-320.
Brogdon WG, McAllister JC: Insecticide resistance and vector control. Emerg Infectious Diseases. 1998, 4 (4): 605-613. 10.3201/eid0404.980410.
Vontas JG, Small GJ, Hemingway J: Glutathione S-transferases as antioxidant defence agents confer pyrethroid resistance in Nilaparvata lugens. Biochem J. 2001, 357 (Pt 1): 65-72. 10.1042/0264-6021:3570065.
Enayati AA, Ranson H, Hemingway J: Insect glutathione transferases and insecticide resistance. Insect Mol Biol. 2005, 14 (1): 3-8. 10.1111/j.1365-2583.2004.00529.x.
Lumjuan N, McCarroll L, Prapanthadara LA, Hemingway J, Ranson H: Elevated activity of an Epsilon class glutathione transferase confers DDT resistance in the dengue vector, Aedes aegypti. Insect Biochem Mol Biol. 2005, 35 (8): 861-871. 10.1016/j.ibmb.2005.03.008.
Rajatileka S, Black WC, Saavedra-Rodriguez K, Trongtokit Y, Apiwathnasorn C, McCall PJ, Ranson H: Development and application of a simple colorimetric assay reveals widespread distribution of sodium channel mutations in Thai populations of Aedes aegypti. Acta Trop. 2008, 108 (1): 54-57. 10.1016/j.actatropica.2008.08.004.
Donnelly MJ, Corbel V, Weetman D, Wilding CS, Williamson MS, Black Wt: Does kdr genotype predict insecticide-resistance phenotype in mosquitoes?. Trends Parasitol. 2009, 25 (5): 213-219. 10.1016/j.pt.2009.02.007.
Anthony N, Rocheleau T, Mocelin G, Lee HJ, Ffrench-Constant R: Cloning, sequencing and functional expression of an acetylcholineesterase gene from the yellow-fever mosquito Aedes aegypti. FEBS Letters. 1995, 368 (3): 461-465. 10.1016/0014-5793(95)00711-H.
Alout H, Berthomieu A, Hadjivassilis A, Weill M: A new amino-acid substitution in acetylcholinesterase 1 confers insecticide resistance to Culex pipiens mosquitoes from Cyprus. Insect Biochem Mol Biol. 2007, 37 (1): 41-47. 10.1016/j.ibmb.2006.10.001.
Bourguet D, Capela R, Raymond M: An insensitive acetylcholinesterase in Culex pipiens (Diptera: Culicidae) from Portugal. J Econ Entomol. 1996, 89 (5): 1060-1066.
Paul A, Harrington LC, Scott JG: Evaluation of novel insecticides for control of dengue vector Aedes aegypti (Diptera: Culicidae). J Med Entomol. 2006, 43 (1): 55-60. 10.1603/0022-2585(2006)043[0055:EONIFC]2.0.CO;2.
Yuen T, Wurmbach E, Pfeffer RL, Ebersole BJ, Sealfon SC: Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays. Nucleic Acids Res. 2002, 30 (10): e48-10.1093/nar/30.10.e48.
Nikou D, Ranson H, Hemingway J: An adult-specific CYP6 P450 gene is overexpressed in a pyrethroid-resistant strain of the malaria vector Anopheles gambiae. Gene. 2003, 318: 91-102. 10.1016/S0378-1119(03)00763-7.
McLaughlin LA, Niazi U, Bibby J, David JP, Vontas J, Hemingway J, Ranson H, Sutcliffe MJ, Paine MJI: Characterization of inhibitors and substrates of Anopheles gambiae CYP6Z2. Insect Mol Biol. 2008, 17 (2): 125-135. 10.1111/j.1365-2583.2007.00788.x.
Chiu TL, Wen ZM, Rupasinghe SG, Schuler MA: Comparative molecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450 capable of metabolizing DDT. Proc Natl Acad Sci USA. 2008, 105 (26): 8855-8860. 10.1073/pnas.0709249105.
Müller P, Chouaibou M, Pignatelli P, Etang J, Walker ED, Donnelly MJ, Simard F, Ranson H: Pyrethroid tolerance is associated with elevated expression of antioxidants and agricultural practice in Anopheles arabiensis sampled from an area of cotton fields in Northern Cameroon. Mol Ecol. 2008, 17 (4): 1145-1155. 10.1111/j.1365-294X.2007.03617.x.
Ding Y, Hawkes N, Meredith J, Eggleston P, Hemingway J, Ranson H: Characterization of the promoters of Epsilon glutathione transferases in the mosquito Anopheles gambiae and their response to oxidative stress. Biochem J. 2005, 387 (Pt 3): 879-888.
Ortelli F, Rossiter LC, Vontas J, Ranson H, Hemingway J: Heterologous expression of four glutathione transferase genes genetically linked to a major insecticide-resistance locus from the malaria vector Anopheles gambiae. Biochem J. 2003, 373 (Pt 3): 957-963. 10.1042/BJ20030169.
Wei SH, Clark AG, Syvanen M: Identification and cloning of a key insecticide-metabolizing glutathione S-transferase (MdGST-6A) from a hyper insecticide-resistant strain of the housefly Musca domestica. Insect Biochem Mol Biol. 2001, 31 (12): 1145-1153. 10.1016/S0965-1748(01)00059-5.
Vaughan A, Hemingway J: Mosquito carboxylesterase Est alpha 2(1) (A2). Cloning and sequence of the full-length cDNA for a major insecticide resistance gene worldwide in the mosquito Culex quinquefasciatus. J Biol Chem. 1995, 270 (28): 17044-17049. 10.1074/jbc.270.28.17044.
Mourya DT, Hemingway J, Leake CJ: Changes in enzymes titers with age in four geographical strains of Aedes aegypti and their association with insecticide resistance. Med Vet Entomol. 1993, 7: 11-16. 10.1111/j.1365-2915.1993.tb00645.x.
Bisset JA, Rodriguez MM, Hemingway J, Diaz C, Small GJ, Ortiz E: Malathion and pyrethroid resistance in Culex quinquefasciatus from Cuba: efficacy of pirimiphos-methyl in the presence of at least three resistance mechanisms. Med Vet Entomol. 1991, 5 (2): 223-228. 10.1111/j.1365-2915.1991.tb00544.x.
Raymond M, Chevillon C, Guillemaud T, Lenormand T, Pasteur N: An overview of the evolution of overproduced esterases in the mosquito Culex pipiens. Royal-Society Discussion Meeting on Insecticide Resistance - from Mechanisms to Management: Apr 08-09 1998; London, England. 1998, 1707-1711.
Boyer S, David JP, Rey D, Lemperiere G, Ravanel P: Response of Aedes aegypti (Diptera: Culicidae) larvae to three xenobiotic exposures: larval tolerance and detoxifying enzyme activities. Environ Toxicol Chem. 2006, 25 (2): 470-476. 10.1897/05-267R2.1.
Diabate A, Baldet T, Chandre F, Akoobeto M, Guiguemde TR, Darriet F, Brengues C, Guillet P, Hemingway J, Small GJ, et al: The role of agricultural use of insecticides in resistance to pyrethroids in Anopheles gambiae s.l. in Burkina Faso. Am J Trop Med Hyg. 2002, 67 (6): 617-622.
Bocquene G, Franco A: Pesticide contamination of the coastline of Martinique. Marine Poll Bull. 2005, 51 (5-7): 612-619. 10.1016/j.marpolbul.2005.06.026.
Hardstone MC, Leichter CA, Scott JG: Multiplicative interaction between the two major mechanisms of permethrin resistance, kdr and cytochrome P450-monooxygenase detoxification, in mosquitoes. J Evol Biol. 2009, 22 (2): 416-423. 10.1111/j.1420-9101.2008.01661.x.
WHO: Guidelines for laboratory and field testing of mosquito larvicides. 2005, Document WHO/CDS/WHOPES/GCDPP/13, Geneva, Switzerland, World Health Organization
WHO: Guidelines for testing mosquito adulticides for indoor residual spraying and treatment of mosquito nets. 2006, Document WHO/CDS/NTD/WHOPES/GCDPP/3, Geneva, Switzerland, World Health Organization
Abbott W: A method of computing the effectiveness of an insecticide. J Econ Entomol. 1925, 18: 265-267.
Finney DJ: Probit analysis. 1971, Cambridge: Cambridge University Press
Raymond M: PROBIT software. CNRS UMII, Licence L93019 Avenix, France. 1993
De Sousa G, Cuany A, Brun A, Amichot M, Rhamani R, Bergé JB: A microfluorimetric method for measuring ethoxycoumarin-O-deethylase activity on individuals Drosophila melanogaster abdomens: Interest for screening resistance in insect populations. An Biochem. 1995, 229: 86-91. 10.1006/abio.1995.1382.
Habig H, Pabst MJ, Jacoby WB: Gluthatione S-transferases: The first step in mercapturic acid formation. J Biol Chem. 1974, 249: 7130-
Van Asperen K: A study of housefly esterases by means of sensitive colorimetric methode. J Insect Physiol. 1962, 8: 401-408. 10.1016/0022-1910(62)90074-4.
Cleveland WS, Devlin SJ: Locally Weighted Regression - An approach to regression-Analysis by local fitting. J Am Stat Assoc. 1988, 83 (403): 596-610. 10.2307/2289282.
Benjamini Y, Hochberg Y: Controlling the False Discovery Rate: a Practical and Powerful Approach to Multiple Testing. J Royal Stat Soc B. 1995, 57: 289-300.
Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucl Acids Res. 2001, 29 (9): 6-10.1093/nar/29.9.e45.