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Exploring the molecular mechanisms of increased intensity of pyrethroid resistance in Central African population of a major malaria vector Anopheles coluzzii

Fadel, Amen N., Ibrahim, SulaimanSadi, Sandeu, Maurice M., Tatsinkou, Claudine Grâce Maffo, Menze, Benjamin D., Irving, Helen, Hearn, Jack, Nagi, Sanjay, Weedall, Gareth D., Terence, Ebai, Tchapga, Williams, Wanji, Samuel and Wondji, Charles ORCID: (2024) 'Exploring the molecular mechanisms of increased intensity of pyrethroid resistance in Central African population of a major malaria vector Anopheles coluzzii'. Evolutionary Applications, Vol 17, Issue 2, e13641.

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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
Subjects: QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 26 Feb 2024 13:45
Last Modified: 26 Feb 2024 13:45


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