Abstract
BackgroundPyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies.ResultsHere, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country.ConclusionPyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-817) contains supplementary material, which is available to authorized users.
Highlights
Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa
Susceptibility status of An. funestus in Zambia The bioassays performed on the An. funestus population from Mbinga (Katete district) in Zambia indicated that this population is highly resistant to both type I and type II pyrethroids, with mortality rates of 15.7 and 5%, respectively, for females (Figure 1)
This profile is significantly different from that in other Southern African populations; full susceptibility to DDT was observed in the Mozambican population, and only moderate resistance was observed in the Malawian population (93% mortality)
Summary
Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Increasing resistance to the available insecticide classes in the major malaria vectors, such as Anopheles funestus, is threatening the effectiveness of these control tools across Africa [2]. The recent WHO Global Plan for Insecticide Resistance Management [2] highlights the growing threat posed by insecticide resistance and calls for urgent action to implement suitable resistance management strategies against malaria vectors to ensure the continued effectiveness of control interventions. The elucidation of the molecular basis of insecticide resistance in malaria vectors is a crucial step in the design and implementation of these resistance management strategies
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