Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa

Author:

Riveron Jacob M12,Ibrahim Sulaiman S13,Mulamba Charles14,Djouaka Rousseau5,Irving Helen1,Wondji Murielle J12,Ishak Intan H16,Wondji Charles S12

Affiliation:

1. Liverpool School of Tropical Medicine, L3 5QA, United Kingdom

2. Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), P.O. Box 288 Yaoundé, Cameroon

3. Department of Biochemistry, Bayero University, PMB 3011 Kano, Nigeria

4. Uganda Virus Research Institute, P.O. Box 49 Entebbe, Uganda

5. International Institute of Tropical Agriculture, Cotonou 08 BP 0932, Benin

6. School of Biological Sciences, Universiti Sains Malaysia, Gelugor, 11800 Penang, Malaysia

Abstract

Abstract Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies.

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology

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