Combined over-expression of two cytochrome P450 genes exacerbates the fitness cost of pyrethroid resistance in the major African malaria vector Anopheles funestus

Tchouakui, Magellan, Mugenzi, Leon M.J., Wondji, Murielle, Tchoupo, Micareme, Njiokou, Flobert and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2021) 'Combined over-expression of two cytochrome P450 genes exacerbates the fitness cost of pyrethroid resistance in the major African malaria vector Anopheles funestus'. Pesticide Biochemistry and Physiology, Vol 173, p. 104772.

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Abstract

Metabolic resistance driven by multiple P450 genes is worsening insecticide resistance in malaria vectors. However, it remains unclear whether such multiple over-expression imposes an additive fitness cost in the vectors. Here, we showed that two highly over-expressed P450 genes (CYP6P9a and CYP6P9b) combine to impose additive fitness costs in pyrethroid-resistant Anopheles funestus. Genotyping of the CYP6P9b resistance allele in hybrid mosquitoes from a pyrethroid-resistant FUMOZ-R and the susceptible FANG strains revealed that this gene imposes a fitness cost in resistant mosquitoes similar to CYP6P9a. Homozygote susceptible CYP6P9b_S (SS) significantly lay more eggs than the resistant (OR = 2.2, P = 0.04) and with greater hatching rate (p < 0.04). Homozygote resistant larvae CYP6P9b_R (RR) developed significantly slower than homozygote susceptible from L1-L4 (χ2 = 7.2; P = 0.007) with a late pupation observed for RR compared to both heterozygotes and homozygotes susceptible (χ 2 = 11.17; P = 0.0008). No difference was observed between genotypes for adult longevity with no change in allele frequency and gene expression across the lifespan. Furthermore, we established that CYP6P9b combines with CYP6P9a to additively exacerbate the fitness cost of pyrethroid resistance with a greater reduction in fecundity/fertility and increased developmental time of double homozygote resistant mosquitoes. Moreover, an increased proportion of double homozygote susceptible individuals was noted over 10 generations in the insecticide-free environment (χ2 = 6.3; P = 0.01) suggesting a reversal to susceptibility in the absence of selection. Such greater fitness cost imposed by multiple P450 genes shows that resistance management strategy based on rotation could help slow the spread of resistance.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.pestbp.2021.104772
Depositing User:	Stacy Murtagh
Date Deposited:	06 Apr 2021 15:26
Last Modified:	03 Aug 2021 13:54
URI:	https://archive.lstmed.ac.uk/id/eprint/17450

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