Genetic Diversity of Cytochrome P450s CYP6M2 and CYP6P4 Associated with Pyrethroid Resistance in the Major Malaria Vectors Anopheles coluzzii and Anopheles gambiae from Yaoundé, Cameroon

Fotso-Toguem, Yvan, Tene-Fossog, Billy, Mugenzi, Leon M. J., Wondji, Murielle, Njiokou, Flobert, Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247 and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2022) 'Genetic Diversity of Cytochrome P450s CYP6M2 and CYP6P4 Associated with Pyrethroid Resistance in the Major Malaria Vectors Anopheles coluzzii and Anopheles gambiae from Yaoundé, Cameroon'. Genes, Vol 14, Issue 1, e52.

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Abstract

Assessing the genetic diversity of metabolic resistance genes, such as cytochrome P450s, helps to understand the dynamics and evolution of resistance in the field. Here, we analyzed the polymorphisms of CYP6M2 and CYP6P4, associated with pyrethroid resistance in Anopheles coluzzii and Anopheles gambiae, to detect potential resistance markers. Field-caught resistant mosquitos and susceptible lab strains were crossed, and F4 was exposed to permethrin for 15 min and 90 min to discriminate highly susceptible (HS) and highly resistant (HR) mosquitos, respectively. Significant permethrin mortality reduction was observed after pre-exposure to PBO, suggesting the gene involvement of P450s. qPCR analysis revealed significant overexpression of CYP6M2 (FC = 19.57 [95% CI 13.96–25.18] for An. coluzzii; 10.16 [7.86–12.46] for An. gambiae) and CYP6P4 (FC = 6.73 [6.15–7.30] An. coluzzii; 23.62 [26.48–20.76] An. gambiae). Full-gene and ≈1 kb upstream were sequenced. For CYP6M2, the upstream region shows low diversity in HR and HS (overall Hd = 0.49, π = 0.018), whereas the full-gene shows allelic-variation but without evidence of ongoing selection. CYP6P4 upstream region showed a lower diversity in HR (Hd = 0.48) than HS (Hd = 0.86) of An. gambiae. These results highlighted that CYP6P4-associated resistance is potentially driven by modification in upstream region. However, further work is needed to determine the real causative variants that will help design rapid detection tools.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 470 Genetic structures QX Parasitology > QX 20 Research (General) QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.3390/genes14010052
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	09 Feb 2023 15:45
Last Modified:	09 Feb 2023 15:45
URI:	https://archive.lstmed.ac.uk/id/eprint/21832

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