Contributions of Cuticle Permeability and Enzyme Detoxification to Pyrethroid Resistance in the Major Malaria Vector Anopheles Gambiae

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 13

PMID 28894186

Citations 64

Authors

Gildas A Yahouedo

Fabrice Chandre

Marie Rossignol

Carole Ginibre

Vasileia Balabanidou

Natacha Garcia Albeniz Mendez

Olivier Pigeon

John Vontas

Sylvie Cornelie

Affiliations

Soon will be listed here.

Abstract

To tackle the problem of insecticide resistance, all resistance mechanisms need to be studied. This study investigated the involvement of the cuticle in pyrethroid resistance in a strain of Anopheles gambiae, MRS, free of kdr mutations. Bioassays revealed MRS to be resistant to pyrethroids and DDT, indicated by increasing knockdown times and resistance ratios. Moreover, biochemical analysis indicated that metabolic resistance based on enhanced CYP450 activity may also play a role. Insecticide penetration assays showed that there were significantly lower amounts of insecticide in the MRS strain than in the susceptible control. Analysis of the levels of the selected transcripts by qPCR showed that CYP6M2, a major pyrethroid metaboliser, CYP4G16, a gene implicated in resistance via its contribution to the biosynthesis of elevated epicuticular hydrocarbons that delay insecticide uptake, and the cuticle genes CPAP3-E and CPLCX1 were upregulated after insecticide exposure. Other metabolic (CYP6P3, GSTe2) and cuticle (CPLCG3, CPRs) genes were also constitutively upregulated. Microscopic analysis showed that the cuticle layers of the MRS strain were significantly thicker than those of the susceptible strain. This study allowed us to assess the contribution made by the cuticle and metabolic mechanisms to pyrethroid resistance in Anopheles gambiae without target-site mutations.

Citing Articles

A Leg Cuticle Protein Enhances the Resistance of Mosquitoes to Deltamethrin.

Li L, Gu L, Tu L, Deng S, Hu J, Zhang Z Int J Mol Sci. 2025; 26(5).

PMID: 40076801 PMC: 11900137. DOI: 10.3390/ijms26052182.

Properties of "Stable" Mosquito Cytochrome P450 Enzymes.

Tzotzos G Insects. 2025; 16(2).

PMID: 40003814 PMC: 11855896. DOI: 10.3390/insects16020184.

Pyrethroid-resistant malaria vector Anopheles gambiae restored susceptibility after pre-exposure to piperonyl-butoxide: results from country-wide insecticide resistance monitoring in Tanzania, 2023.

Kabula B, Mlacha Y, Serbantez N, Nhiga S, Mkude S, Kiware S Malar J. 2024; 23(1):395.

PMID: 39709444 PMC: 11663351. DOI: 10.1186/s12936-024-05211-7.

Insecticide resistance and its intensity in urban Anopheles arabiensis in Kisumu City, Western Kenya: Implications for malaria control in urban areas.

Machani M, Nzioki I, Onyango S, Onyango B, Githure J, Atieli H PLoS One. 2024; 19(11):e0303921.

PMID: 39536003 PMC: 11560014. DOI: 10.1371/journal.pone.0303921.

Efficacy of PermaNet Dual compared to Interceptor G2 and PermaNet 3.0 in experimental huts in Siaya County, western Kenya.

Ogutu N, Agumba S, Moshi V, Onyango P, Ouma C, Ramaita E Malar J. 2024; 23(1):326.

PMID: 39488707 PMC: 11531690. DOI: 10.1186/s12936-024-05157-w.

References

Etang J, Pennetier C, Piameu M, Bouraima A, Chandre F, Awono-Ambene P . When intensity of deltamethrin resistance in Anopheles gambiae s.l. leads to loss of Long Lasting Insecticidal Nets bio-efficacy: a case study in north Cameroon. Parasit Vectors. 2016; 9:132. PMC: 4782322. DOI: 10.1186/s13071-016-1420-x. View

Tetreau G, Dittmer N, Cao X, Agrawal S, Chen Y, Muthukrishnan S . Analysis of chitin-binding proteins from Manduca sexta provides new insights into evolution of peritrophin A-type chitin-binding domains in insects. Insect Biochem Mol Biol. 2014; 62:127-41. PMC: 9346963. DOI: 10.1016/j.ibmb.2014.12.002. View

Riveron J, Irving H, Ndula M, Barnes K, Ibrahim S, Paine M . Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus. Proc Natl Acad Sci U S A. 2012; 110(1):252-7. PMC: 3538203. DOI: 10.1073/pnas.1216705110. View

Martinez-Torres D, Chandre F, Williamson M, Darriet F, Berge J, Devonshire A . Molecular characterization of pyrethroid knockdown resistance (kdr) in the major malaria vector Anopheles gambiae s.s. Insect Mol Biol. 1998; 7(2):179-84. DOI: 10.1046/j.1365-2583.1998.72062.x. View

Sougoufara S, Diedhiou S, Doucoure S, Diagne N, Sembene P, Harry M . Biting by Anopheles funestus in broad daylight after use of long-lasting insecticidal nets: a new challenge to malaria elimination. Malar J. 2014; 13:125. PMC: 3973838. DOI: 10.1186/1475-2875-13-125. View

Gibbs A . Lipid melting and cuticular permeability: new insights into an old problem. J Insect Physiol. 2003; 48(4):391-400. DOI: 10.1016/s0022-1910(02)00059-8. View

Ortelli F, Rossiter L, 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):957-63. PMC: 1223529. DOI: 10.1042/BJ20030169. View

Koffi A, Alou L, Adja M, Chandre F, Pennetier C . Insecticide resistance status of Anopheles gambiae s.s population from M'Bé: a WHOPES-labelled experimental hut station, 10 years after the political crisis in Côte d'Ivoire. Malar J. 2013; 12:151. PMC: 3658939. DOI: 10.1186/1475-2875-12-151. View

Ahmad M, Denholm I, Bromilow R . Delayed cuticular penetration and enhanced metabolism of deltamethrin in pyrethroid-resistant strains of Helicoverpa armigera from China and Pakistan. Pest Manag Sci. 2006; 62(9):805-10. DOI: 10.1002/ps.1225. View

10.

Wood O, Hanrahan S, Coetzee M, Koekemoer L, Brooke B . Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus. Parasit Vectors. 2010; 3:67. PMC: 2924294. DOI: 10.1186/1756-3305-3-67. View

11.

Benoit J, Lopez-Martinez G, Phillips Z, Patrick K, Denlinger D . Heat shock proteins contribute to mosquito dehydration tolerance. J Insect Physiol. 2009; 56(2):151-6. PMC: 2861860. DOI: 10.1016/j.jinsphys.2009.09.012. View

12.

Tillman J, Seybold S, Jurenka R, Blomquist G . Insect pheromones--an overview of biosynthesis and endocrine regulation. Insect Biochem Mol Biol. 1999; 29(6):481-514. DOI: 10.1016/s0965-1748(99)00016-8. View

13.

Toe K, NFale S, Dabire R, Ranson H, Jones C . The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi in West Africa is linked to increased expression of multiple gene families. BMC Genomics. 2015; 16:146. PMC: 4352231. DOI: 10.1186/s12864-015-1342-6. View

14.

Behr M, Hoch M . Identification of the novel evolutionary conserved obstructor multigene family in invertebrates. FEBS Lett. 2005; 579(30):6827-33. DOI: 10.1016/j.febslet.2005.11.021. View

15.

Mitchell S, Stevenson B, Muller P, Wilding C, Egyir-Yawson A, Field S . Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana. Proc Natl Acad Sci U S A. 2012; 109(16):6147-52. PMC: 3341073. DOI: 10.1073/pnas.1203452109. View

16.

Liu N . Insecticide resistance in mosquitoes: impact, mechanisms, and research directions. Annu Rev Entomol. 2015; 60:537-59. DOI: 10.1146/annurev-ento-010814-020828. View

17.

Raymond M, Heckel D, Scott J . Interactions between pesticide genes: model and experiment. Genetics. 1989; 123(3):543-51. PMC: 1203826. DOI: 10.1093/genetics/123.3.543. View

18.

Stevenson B, Bibby J, Pignatelli P, Muangnoicharoen S, ONeill P, Lian L . Cytochrome P450 6M2 from the malaria vector Anopheles gambiae metabolizes pyrethroids: Sequential metabolism of deltamethrin revealed. Insect Biochem Mol Biol. 2011; 41(7):492-502. DOI: 10.1016/j.ibmb.2011.02.003. View

19.

Chandre F, Darriet F, Duchon S, Finot L, Manguin S, Carnevale P . Modifications of pyrethroid effects associated with kdr mutation in Anopheles gambiae. Med Vet Entomol. 2000; 14(1):81-8. DOI: 10.1046/j.1365-2915.2000.00212.x. View

20.

Vontas J, David J, Nikou D, Hemingway J, Christophides G, Louis C . Transcriptional analysis of insecticide resistance in Anopheles stephensi using cross-species microarray hybridization. Insect Mol Biol. 2007; 16(3):315-24. DOI: 10.1111/j.1365-2583.2007.00728.x. View