GEPHE SUMMARY Print
Entry Status
Published
GepheID
GP00000208
Main curator
Martin
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Anopheles funestus - Southern Africa - sensitive to pyrethroids
Trait State in Taxon B
Anopheles funestus - Southern Africa - resistant to pyrethroids
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Common Name
African malaria mosquito
Synonyms
African malaria mosquito; Anopheles funestus Giles, 1900
Rank
species
Lineage
Show more ... Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Holometabola; Diptera; Nematocera; Culicomorpha; Culicoidea; Culicidae; Anophelinae; Anopheles; Cellia; Myzomyia; funestus group; funestus subgroup
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
African malaria mosquito
Synonyms
African malaria mosquito; Anopheles funestus Giles, 1900
Rank
species
Lineage
Show more ... Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Holometabola; Diptera; Nematocera; Culicomorpha; Culicoidea; Culicidae; Anophelinae; Anopheles; Cellia; Myzomyia; funestus group; funestus subgroup
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
CYP2C9
Synonyms
CPC9; CYP2C; CYP2C10; CYPIIC9; P450IIC9
Sequence Similarities
Belongs to the cytochrome P450 family.
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
Molecular Type
Aberration Type
Molecular Details of the Mutation
unknown but strong evidence of directional selection at these genes correlated with elevated expression
Experimental Evidence
Authors
Riveron JM; Irving H; Ndula M; Barnes KG; Ibrahim SS; Paine MJ; Wondji CS
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 the main 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.
Additional References
RELATED GEPHE
Related Haplotypes
No matches found.
EXTERNAL LINKS
COMMENTS
YOUR FEEDBACK is welcome!