Multi-insecticide resistant malaria vectors in the field remain susceptible to malathion, despite the presence of Ace1 point mutations

PLoS Genet. 2022 Feb 10;18(2):e1009963. doi: 10.1371/journal.pgen.1009963. eCollection 2022 Feb.


Insecticide resistance in Anopheles mosquitoes is seriously threatening the success of insecticide-based malaria vector control. Surveillance of insecticide resistance in mosquito populations and identifying the underlying mechanisms enables optimisation of vector control strategies. Here, we investigated the molecular mechanisms of insecticide resistance in three Anopheles coluzzii field populations from southern Côte d'Ivoire, including Agboville, Dabou and Tiassalé. All three populations were resistant to bendiocarb, deltamethrin and DDT, but not or only very weakly resistant to malathion. The absence of malathion resistance is an unexpected result because we found the acetylcholinesterase mutation Ace1-G280S at high frequencies, which would typically confer cross-resistance to carbamates and organophosphates, including malathion. Notably, Tiassalé was the most susceptible population to malathion while being the most resistant one to the pyrethroid deltamethrin. The resistance ratio to deltamethrin between Tiassalé and the laboratory reference colony was 1,800 fold. By sequencing the transcriptome of individual mosquitoes, we found numerous cytochrome P450-dependent monooxygenases - including CYP6M2, CYP6P2, CYP6P3, CYP6P4 and CYP6P5 - overexpressed in all three field populations. This could be an indication for negative cross-resistance caused by overexpression of pyrethroid-detoxifying cytochrome P450s that may activate pro-insecticides, thereby increasing malathion susceptibility. In addition to the P450s, we found several overexpressed carboxylesterases, glutathione S-transferases and other candidates putatively involved in insecticide resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Animals
  • Anopheles / drug effects
  • Anopheles / genetics*
  • Cote d'Ivoire / epidemiology
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Expression / genetics
  • Insecticide Resistance / genetics*
  • Insecticides / pharmacology
  • Malaria / prevention & control
  • Malaria / transmission
  • Malathion / metabolism
  • Malathion / pharmacology*
  • Mixed Function Oxygenases / genetics
  • Mosquito Control
  • Mosquito Vectors / genetics
  • Point Mutation
  • Transcriptome / genetics


  • Insecticides
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Acetylcholinesterase
  • Malathion

Grant support

This work was funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme: ICT-39-2015 - International partnership building in low and middle income countries (Grant Agreement No. 688207 – DMC-MALVEC) to KM, JV and PMR; and the Novartis Foundation for Medical-Biological Research (No. 19B134) to NW and PMR. The Voluntary Academic Society Basel / Freiwillige Akademische Gesellschaft Basel (FAG) and the Rudolf Geigy Foundation / R. Geigy-Stiftung supported NW. We are thankful for the support by the Research Infrastructures for the control of vector-borne diseases that has received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 731060 – Infravec2). Infravec2 sponsored the RNA sequencing at the Polo GGB facility in Siena, Italy and bioinformatics support at FORTH IMBB, Greece. The Inferavec2 grant was awarded to NW (Grant No. 5505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.