Abstract

Insecticides remain a main tool for the control of arthropod vectors. The urgency to prevent the insurgence of insecticide resistance and the perspective to find new target sites, for the development of novel molecules, are fuelling the study of the molecular mechanisms involved in insect defence against xenobiotic compounds. In this study, we have investigated if ATP-binding cassette (ABC) transporters, a major component of the defensome machinery, are involved in defence against the insecticide permethrin, in susceptible larvae of the malaria vector Anopheles gambiae sensu stricto. Bioassays were performed with permethrin alone, or in combination with an ABC transporter inhibitor. Then we have investigated the expression profiles of five ABC transporter genes at different time points following permethrin exposure, to assess their expression patterns across time. The inhibition of ABC transporters increased the larval mortality by about 15-fold. Likewise, three genes were up-regulated after exposure to permethrin, showing different patterns of expression across the 48 h. Our results provide the first evidences of ABC transporters involvement in defence against a toxic in larvae of An. gambiae s.s. and show that the gene expression response is modulated across time, being continuous, but stronger at the earliest and latest times after exposure.

Highlights

  • Vector-borne diseases, caused by pathogens and parasites transmitted by bloodsucking arthropods, such as mosquitoes, sandflies, ticks, and tse-tse flies, are a major threat to human health and well-being [1]

  • These results indicate that this ABCG transporter is likely to play an important role in different mosquito species as a defence system against different insecticides

  • 2 hours after treatment and its up-regulation persisted until 48 h maintaining similar values across time, to the ABCC-AGAP006427 gene (Figure 1). These results showed the occurrence of a modulated response of the ATP-binding cassette (ABC) transporter genes across time, where each single gene is up- or down-regulated during insecticide exposure at different time-points, and up-regulation of multiple genes occurs at different time-points

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Summary

Introduction

Vector-borne diseases, caused by pathogens and parasites transmitted by bloodsucking arthropods, such as mosquitoes, sandflies, ticks, and tse-tse flies, are a major threat to human health and well-being [1]. Detoxification in insects is achieved through an array of protein systems, including detoxifying enzymes and efflux pump transporters [7,8,9,10,11]. The inhibition of detoxifying efflux pumps has been shown to increase the susceptibility to insecticides in several arthropod species, including malaria vectors [7,8,9,10]. Combined treatments of insecticides with inhibitors of efflux pump transporters could allow to reduce the dose and frequency of insecticide applications and to generate a cascade of positive effects (e.g., reduction of the risk of resistance development, minor pesticide pollution and reduced damage to non-target fauna) [12,13]

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