Transcriptomic analysis and molecular docking reveal genes involved in the response of Aedes aegypti larvae to an essential oil extracted from Eucalyptus.

Ivana Sierra,Ariel Aptekmann,Paula V. Gonzalez,Lucila Traverso,Sheila Ons,Jose Manuel Latorre-Estivalis,Héctor Masuh,Alejandro Daniel Nadra,Adly M. M. Abd-Alla

doi:10.1371/journal.pntd.0009587

Abstract

BackgroundAedes aegypti (L.) is an urban mosquito, vector of several arboviruses that cause severe diseases in hundreds of million people each year. The resistance to synthetic insecticides developed by Ae. aegypti populations worldwide has contributed to failures in vector control campaigns, increasing the impact of arbovirus diseases. In this context, plant-derived essential oils with larvicidal activity could be an attractive alternative for vector control. However, the mode of action and the detoxificant response of mosquitoes to plant derived compounds have not been established, impairing the optimization of their use.Methods and findingsHere we compare gene expression in Ae. aegypti larvae after 14 hrs of exposure to Eucalyptus camaldulensis essential oil with a control group exposed to vehicle (acetone) for the same lapse, by using RNA-Seq. We found differentially expressed genes encoding for cuticle proteins, fatty-acid synthesis, membrane transporters and detoxificant related gene families (i.e. heat shock proteins, cytochromes P450, glutathione transferases, UDP-glycosyltransferases and ABC transporters). Finally, our RNA-Seq and molecular docking results provide evidence pointing to a central involvement of chemosensory proteins in the detoxificant response in mosquitoes.Conclusions and significanceOur work contributes to the understanding of the physiological response of Ae. aegypti larvae to an intoxication with a natural toxic distilled from Eucalyptus leafs. The results suggest an involvement of most of the gene families associated to detoxification of xenobiotics in insects. Noteworthy, this work provides important information regarding the implication of chemosensory proteins in the detoxification of a natural larvicide. Understanding the mode of detoxification of Eucalyptus distilled compounds could contribute to their implementation as a tool in mosquito control.

Highlights

Aedes aegypti is an urban mosquito, vector of several arboviruses that cause diseases such as dengue, chikungunya, zika and yellow fever
Insecticide resistance developed by some Ae. aegypti populations worldwide is an important reason for the failures to control the spreading of arbovirus diseases [2]
Insects were housed, cared, fed and handled in accordance with resolution 1047/2005 (Consejo Nacional de Investigaciones Cientıficas y Tecnicas, CONICET, Argentina) regarding the national reference ethical framework for biomedical research with laboratory, farm, and nature collected animals, which is in accordance with the standard procedures of the Office for Laboratory Animal Welfare, Department of Health and Human Services, NIH and the recommendations established by the 2010/63/EU Directive of the European Parliament, related to the protection of animals used for scientific purposes

Summary

Introduction

Aedes aegypti is an urban mosquito, vector of several arboviruses that cause diseases such as dengue, chikungunya, zika and yellow fever. Given the distribution of Ae. aegypti in tropical and sub-tropical areas worldwide, about half of humanity is at risk of contracting a virus transmitted by this vector; the control of mosquito populations is the preferred method for limiting infection rates With this objective, neurotoxic insecticides such as organophosphates or pyrethroids are used. The presence of pollutants in the environment could activate detoxificant mechanisms that confer tolerance to insecticides to mosquitoes [4] In this context, the implementation of an integrated vector management (IVM) strategy and the development of alternative tools for the control of mosquito populations are urgent [5]. The resistance to synthetic insecticides developed by Ae. aegypti populations worldwide has contributed to failures in vector control campaigns, increasing the impact of arbovirus diseases In this context, plant-derived essential oils with larvicidal activity could be an attractive alternative for vector control. The mode of action and the detoxificant response of mosquitoes to plant derived compounds have not been established, impairing the optimization of their use

Methods

Results

Conclusion