Abstract
Malaria causes more than 300 million clinical cases and 665,000 deaths each year, and the majority of the mortality and morbidity occurs in sub-Saharan Africa. Due to the lack of effective vaccines and wide-spread resistance to antimalarial drugs, mosquito control is the primary method of malaria prevention and control. Currently, malaria vector control relies on the use of insecticides, primarily pyrethroids. The extensive use of insecticides has imposed strong selection pressures for resistance in the mosquito populations. Consequently, resistance to pyrethroids in Anopheles gambiae, the main malaria vector in sub-Saharan Africa, has become a major obstacle for malaria control. A key element of resistance management is the identification of resistance mechanisms and subsequent development of reliable resistance monitoring tools. Field-derived An. gambiae from Western Kenya were phenotyped as deltamethrin-resistant or -susceptible by the standard WHO tube test, and their expression profile compared by RNA-seq. Based on the current annotation of the An. gambiae genome, a total of 1,093 transcripts were detected as significantly differentially accumulated between deltamethrin-resistant and -susceptible mosquitoes. These transcripts are distributed over the entire genome, with a large number mapping in QTLs previously linked to pyrethorid resistance, and correspond to heat-shock proteins, metabolic and transport functions, signal transduction activities, cytoskeleton and others. The detected differences in transcript accumulation levels between resistant and susceptible mosquitoes reflect transcripts directly or indirectly correlated with pyrethroid resistance. RNA-seq data also were used to perform a de-novo Cufflinks assembly of the An. gambiae genome.
Highlights
The use of insecticides has been central to the fight against malaria, a disease that causes annually 665,000 deaths most in sub-Saharan Africa [1]
We examined here the expression profile of deltamethrinsusceptible and resistant mosquitoes, as defined through the standard WHO tube bioassay [35]
Susceptibility to Deltamethrin and kdr Genotype PYs, primarily deltamethrin, are the main insecticides used in the study areas (File S2)
Summary
The use of insecticides has been central to the fight against malaria, a disease that causes annually 665,000 deaths most in sub-Saharan Africa [1]. Pyrethroids (PYs) are the choice of insecticides for indoor-residual spray (IRS) and impregnating bednets because they meet the low toxicity and high efficacy requirements [2]. The extensive use of PYs imposes strong selection pressures on mosquito populations for increased resistance. PYs resistance and cross-resistance between PYs and DDT have been detected in Africa [3]. Insecticide resistance management is crucial for the success of malaria control, and subsequently, to promote economic development of malaria endemic countries. A key element of resistance management is the determination of resistance mechanisms in the malaria vectors [4]
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