Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Yvan Gaetan Fotso-Toguem
ORCID logo ,
Billy Tene-Fossog
* ,
Leon M.J. Mugenzi
,
Murielle J. Wondji
,
Flobert Njiokou
,
Hilary Ranson
ORCID logo ,
Charles S. Wondji
ORCID logo
Version 1 : Received: 21 November 2022 / Approved: 25 November 2022 / Online: 25 November 2022 (05:51:07 CET)

A peer-reviewed article of this Preprint also exists.

Fotso-Toguem, Y.; Tene-Fossog, B.; Mugenzi, L.M.J.; Wondji, M.J.; Njiokou, F.; Ranson, H.; Wondji, C.S. 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 2023, 14, 52. Fotso-Toguem, Y.; Tene-Fossog, B.; Mugenzi, L.M.J.; Wondji, M.J.; Njiokou, F.; Ranson, H.; Wondji, C.S. 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 2023, 14, 52.

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 analysed the polymor-phisms of CYP6M2 and CYP6P4 associated with pyrethroid resistance in Anopheles coluzzii and An. gambiae, to detect potential resistance markers. Field-caught resistant mosquitoes and susceptible lab-strains were crossed and F4 was exposed to permethrin for 15min and 90min to discriminate highly susceptible (HS) and highly resistant (HR) mosquitoes respectively. Significant permethrin mortality reduction was observed after pre-exposure to PBO, suggesting P450s genes involvement. QPCR analysis revealed significant over-expression 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 ≈1kb upstream were sequenced. For CYP6M2, 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 which will help design rapid detec-tion tools.

Keywords

CYP6M2; CYP6P4; polymorphism; metabolic resistance; pyrethroid; Anopheles coluzzii; Anopheles gambiae

Subject

Biology and Life Sciences, Insect Science

Copyright: 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.

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