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Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus

Riveron Miranda, Jacob ORCID: https://orcid.org/0000-0002-5395-767X, Irving, Helen, Ndula, Miranda, Barnes, Kayla, Ibrahim, SulaimanSadi, Paine, M. J. I. ORCID: https://orcid.org/0000-0003-2061-7713 and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2013) 'Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles funestus'. Proceedings of the National Academy of Sciences, Vol 110, Issue 1, pp. 252-257.

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Abstract

Pyrethroid insecticides are critical for malaria control in Africa. However, resistance to this insecticide class in the malaria vector Anopheles funestus is spreading rapidly across Africa, threatening the success of ongoing and future malaria control programs. The underlying resistance mechanisms driving the spread of this resistance in wild populations remain largely unknown. Here, we show that increased expression of two tandemly duplicated P450 genes, CYP6P9a and CYP6P9b, is themain mechanism driving pyrethroid resistance in Malawi and Mozambique, two southern African countries where this insecticide class forms the mainstay of malaria control. Genome-wide transcription analysis using microarray and quantitative RT-PCR consistently revealed that CYP6P9a and CYP6P9b are the two genes most highly overexpressed (>50-fold; q < 0.01) in permethrin-resistant mosquitoes. Transgenic expression of CYP6P9a and CYP6P9b in Drosophila melanogaster demonstrated that elevated expression of either of these genes confers resistance to both type I (permethrin) and type II (deltamethrin) pyrethroids. Functional characterization of recombinant CYP6P9b confirmed that this protein metabolized both type I (permethrin and
bifenthrin) and type II (deltamethrin and Lambda-cyhalothrin) pyrethroids but not DDT. Variability analysis identified that a single allele of each of these genes is predominantly associated with pyrethroid resistance in field populations from both countries, which is suggestive of a single origin of this resistance that has since spread across the region. Urgent resistance management strategies should be implemented in this region to limit a further spread of this resistance and minimize its impact on the success of ongoing malaria control programs.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 470 Genetic structures
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1216705110
Depositing User: Users 183 not found.
Date Deposited: 16 Apr 2013 10:12
Last Modified: 06 Feb 2018 13:05
URI: http://archive.lstmed.ac.uk/id/eprint/3087

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