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

Nadja C Wipf,Behi K Fodjo,Christabelle G Sadia,France-Paraudie A Kouadio,John Vontas,Wandrille Duchemin,Konstantinos Mavridis,Pie Müller,Chouaïbou S Mouhamadou,Laura Vavassori,Pascal Mäser,Subba Reddy Palli

doi:10.1371/journal.pgen.1009963

Abstract

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.

Highlights

Insecticide-based vector control interventions – primarily insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) – have saved millions of lives from malaria and other vector-borne diseases across Africa [1,2]
Surveillance of insecticide resistance and understanding the underlying molecular mechanisms are key for choosing effective vector control strategies
Our key finding was that these multi-insecticide resistant malaria vectors largely remained susceptible to malathion, despite the presence of a mutation in the target enzyme of this organophosphate insecticide that would typically confer resistance

Summary

Introduction

Insecticide-based vector control interventions – primarily insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) – have saved millions of lives from malaria and other vector-borne diseases across Africa [1,2]. The resulting emergence and rapid spread of insecticide resistant Anopheles mosquitoes are seriously threatening the success of malaria control efforts [3,4]. A crucial challenge is to maintain the efficacy of current interventions by delaying and managing insecticide resistance as well as bringing new control tools to the market. Surveillance of insecticide susceptibility in mosquito populations is key to guide vector control strategies in order to make them as effective and sustainable as possible [5]. Understanding the underlying genomic alterations helps identifying the risk for cross-resistance and is fundamental to define the most potent insecticide resistance management (IRM) strategy in a given setting [5,6]

Methods

Results

Discussion

Conclusion