Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

Mugenzi, Leon M J, Menze, Benjamin, Tchouakui, Magellan, Wondji, Murielle, Irving, Helen, Tchoupo, Micareme, Hearn, Jack ORCID: https://orcid.org/0000-0003-3358-4949, Weedall, Gareth ORCID: https://orcid.org/0000-0002-8927-1063, Riveron, Jacob ORCID: https://orcid.org/0000-0002-5395-767X and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2019) 'Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus'. Nature Communications, Vol 10, Issue 4652.

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Abstract

Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay, we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids helping improve resistance management.

Item Type:	Article
Subjects:	QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs 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) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-019-12686-5
Depositing User:	Samantha Sheldrake
Date Deposited:	14 Oct 2019 10:47
Last Modified:	16 Mar 2021 15:45
URI:	https://archive.lstmed.ac.uk/id/eprint/12698

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