Dataset Information

Contributions of cuticle permeability and enzyme detoxification to pyrethroid resistance in the major malaria vector Anopheles gambiae.

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.

SUBMITTER: Yahouedo GA

PROVIDER: S-EPMC5593880 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Contributions of cuticle permeability and enzyme detoxification to pyrethroid resistance in the major malaria vector Anopheles gambiae.

Yahouédo Gildas A GA Chandre Fabrice F Rossignol Marie M Ginibre Carole C Balabanidou Vasileia V Mendez Natacha Garcia Albeniz NGA Pigeon Olivier O Vontas John J Cornelie Sylvie S

Scientific reports 20170911 1

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 pe ...[more]

PMID: 28894186

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Project description:Changes in global temperature are impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes, including chromosomal inversions and overexpression and/or changes in allele frequencies of thermotolerance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investigated the impact of thermotolerance on pyrethroid resistance in four populations of the malaria vector An. gambiae s.l., from the savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae s.s. were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38 °C, and LT50 of ~44 °C. Significantly high permethrin resistance was observed (mortality < 50%) in 44 °C heat-hardened (exposure to an intermediately high temperature provides protection to a more severe temperature or insecticide) larvae from two sites, BUK and Pantami, compared with the control, and heat-hardened adult females from Auyo (mortality = 3.00% ± 1.20, χ2 = 5.83, p < 0.01) compared with the control (12.00% ± 4.65). The 2La chromosomal inversion was detected at ~50% in subset of larvae and 58% in subset of adult females genotyped. A significant association was observed (OR = 7.2, p < 0.03) between permethrin resistance and the 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites, permethrin resistance correlated with 2La/a homozygosity in adult females (R = 5.02, p = 0.01). qRT-PCR identified six genes commonly induced/overexpressed, including the heat shock protein 70 (AGAP004581) which was 2468× and 5× overexpressed in heat-hardened and permethrin-resistant females, respectively; trehalose-6-phosphate synthase (AGAP008227); and the ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for the design/choice of control measures.

Dataset Information

Contributions of cuticle permeability and enzyme detoxification to pyrethroid resistance in the major malaria vector Anopheles gambiae.

Publications

Contributions of cuticle permeability and enzyme detoxification to pyrethroid resistance in the major malaria vector Anopheles gambiae.

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