Fadel, AN, Ibrahim, SS, Sandeu, MM, Tatsinkou, CGM, Menze, BD, Irving, H, Hearn, J, Nagi, SC, Weedall, GD, Terence, E, Tchapga, W, Wanji, S and Wondji, CS (2024) Exploring the molecular mechanisms of increased intensity of pyrethroid resistance in Central African population of a major malaria vector Anopheles coluzzii. Evolutionary Applications, 17 (2). pp. 1-16. ISSN 1752-4563

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Abstract

Molecular mechanisms driving the escalation of pyrethroid resistance in the major malaria mosquitoes of Central Africa remain largely uncharacterized, hindering effective management strategies. Here, resistance intensity and the molecular mechanisms driving it were investigated in a population of Anopheles coluzzii from northern Cameroon. High levels of pyrethroid and organochloride resistance were observed in An. coluzzii population, with no mortality for 1× permethrin; only 11% and 33% mortalities for 5× and 10× permethrin diagnostic concentrations, and <2% mortalities for deltamethrin and DDT, respectively. Moderate bendiocarb resistance (88% mortality) and full susceptibility to malathion were observed. Synergist bioassays with piperonyl butoxide recovered permethrin susceptibility, with mortalities increasing to 53.39%, and 87.30% for 5× and 10× permethrin, respectively, implicating P450 monooxygenases. Synergist bioassays with diethyl maleate (DEM) recovered permethrin and DDT susceptibilities (mortalities increasing to 34.75% and 14.88%, respectively), implicating glutathione S-transferases. RNA-seq-based genome-wide transcriptional analyses supported by quantitative PCR identified glutathione S-transferase, GSTe2 (RNA-seqFC = 2.93 and qRT-PCRFC = 8.4, p < 0.0043) and CYP450, CYP6Z2 (RNA-seqFC = 2.39 and qRT-PCRFC = 11.7, p < 0.0177) as the most overexpressed detoxification genes in the pyrethroid-resistant mosquitoes, compared to mosquitoes of the susceptible Ngousso colony. Other overexpressed genes include P450s, CYP6M2 (FC = 1.68, p < 0.0114), CYP4G16 (FC = 2.02, p < 0.0005), and CYP4G17 (FC = 1.86, p < 0.0276). While high frequency of the 1014F kdr mutation (50%) and low frequencies of 1014S (6.61%) and 1575Y (10.29%) were observed, no ace-1 mutation was detected in bendiocarb-resistant populations, suggesting the preeminent role of metabolic mechanism. Overexpression of metabolic resistance genes (including GSTe2 and CYP6Z2 known to confer resistance to multiple insecticides) in An. coluzzii from the Sudan Savannah of Cameroon highlights the need for alternative management strategies to reduce malaria burden in northern Cameroon

Item Type:	Article
Uncontrolled Keywords:	Anopheles coluzzii; Cameroon; insecticide; metabolic; resistance; 0304 Medicinal and Biomolecular Chemistry; 0603 Evolutionary Biology; 0604 Genetics
Subjects:	G Geography. Anthropology. Recreation > GE Environmental Sciences Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology
Divisions:	Biological & Environmental Sciences (from Sep 19)
Publisher:	Wiley Open Access
SWORD Depositor:	A Symplectic
Date Deposited:	04 Mar 2024 09:56
Last Modified:	04 Mar 2024 10:00
DOI or ID number:	10.1111/eva.13641
URI:	https://researchonline.ljmu.ac.uk/id/eprint/22724

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