Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa

Ibrahim, Sulaiman S.; Amvongo-Adjia, Nathalie; Wondji, Murielle J.; Irving, Helen; Riveron, Jacob M.; Wondji, Charles S.

doi:10.3390/genes9030140

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa

Sulaiman S. Ibrahim

^1,2,*

Nathalie Amvongo-Adjia

^3,4

^1,3,

¹,

^1,3 and

^1,3,*

Vector Biology Department, Liverpool School of Tropical Medicine (LSTM), Liverpool L3 5QA, UK

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

LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), P.O. Box 13591, Yaoundé, Cameroon

⁴

Centre for Medical Research, Institute of Medical Research and Medicinal Plants Studies (IMPM), P.O. Box 13033, Yaoundé, Cameroon

Authors to whom correspondence should be addressed.

Genes 2018, 9(3), 140; https://doi.org/10.3390/genes9030140

Received: 13 January 2018 / Revised: 24 February 2018 / Accepted: 28 February 2018 / Published: 2 March 2018

(This article belongs to the Section Animal Genetics and Genomics)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

Resistance to pyrethroids (the ingredients in bed net insecticides) in the major malaria vector Anopheles funestus is threatening recent gains in the fight against malaria. Here, we established the role of an over-expressed P450, A. funestus CYP6AA1 in insecticides resistance. Transcription profiling of CYP6AA1 across Africa using microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that it is significantly more over-expressed in southern African populations compared to West (Benin) and East African (Uganda). Heterologous expression in Escherichia coli coupled with metabolism assays demonstrated that CYP6AA1 metabolises type I (permethrin) and type II (deltamethrin) pyrethroids, as well as bendiocarb (a carbamate). Transgenic Drosophila melanogaster flies over-expressing CYP6AA1 were significantly more resistant to pyrethroid insecticides, permethrin and deltamethrin compared with control flies not expressing the gene, validating the role of this gene in pyrethroid resistance. In silico modelling and docking simulations predicted the intermolecular receptor-ligand interactions which allow this P450 to metabolise the pyrethroids and bendiocarb. Validation of CYP6AA1 as a pyrethroid resistance gene makes it possible to monitor the spread of resistance in the field where this P450 is over-expressed. Its potential cross-resistance role makes it necessary to monitor the gene closely to inform control programs on molecular basis of multiple resistance in the field. View Full-Text

Keywords: Anopheles funestus; CYP6AA1; overexpression; pyrethroids; bendiocarb; resistance

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
Supplementary (ZIP, 1823 KiB)

Share and Cite

MDPI and ACS Style

Ibrahim, S.S.; Amvongo-Adjia, N.; Wondji, M.J.; Irving, H.; Riveron, J.M.; Wondji, C.S. Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa. Genes 2018, 9, 140. https://doi.org/10.3390/genes9030140

AMA Style

Ibrahim SS, Amvongo-Adjia N, Wondji MJ, Irving H, Riveron JM, Wondji CS. Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa. Genes. 2018; 9(3):140. https://doi.org/10.3390/genes9030140

Chicago/Turabian Style

Ibrahim, Sulaiman S., Nathalie Amvongo-Adjia, Murielle J. Wondji, Helen Irving, Jacob M. Riveron, and Charles S. Wondji. 2018. "Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa" Genes 9, no. 3: 140. https://doi.org/10.3390/genes9030140

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Pyrethroid Resistance in the Major Malaria Vector Anopheles funestus is Exacerbated by Overexpression and Overactivity of the P450 CYP6AA1 Across Africa

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI