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Silencing of P-glycoprotein increases mortality in temephos-treated Aedes aegypti larvae

Authors

  • J. Figueira-Mansur,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
    2. Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Rio de Janeiro, RJ, Brazil
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  • A. Ferreira-Pereira,

    1. Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo Góes, Rio de Janeiro, RJ, Brazil
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  • J. F. Mansur,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
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  • T. A. Franco,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
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  • E. S. L. Alvarenga,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
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  • M. H. F. Sorgine,

    1. Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Rio de Janeiro, RJ, Brazil
    2. Instituto Nacional de Ciência e Tecnologia em Entomologia , Molecular, Brazil
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  • B. C. Neves,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
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  • A. C. A. Melo,

    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
    2. Instituto Nacional de Ciência e Tecnologia em Entomologia , Molecular, Brazil
    3. Honorary Maeda-Duffey Laboratory, University of California Davis, Davis, CA, USA
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  • W. S. Leal,

    1. Honorary Maeda-Duffey Laboratory, University of California Davis, Davis, CA, USA
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  • H. Masuda,

    1. Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Rio de Janeiro, RJ, Brazil
    2. Instituto Nacional de Ciência e Tecnologia em Entomologia , Molecular, Brazil
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  • M. F. Moreira

    Corresponding author
    1. Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil
    2. Instituto Nacional de Ciência e Tecnologia em Entomologia , Molecular, Brazil
    • Correspondence: Monica F. Moreira, Laboratório de Bioquímica e Biologia Molecular de Vetores, Departamento de Bioquímica, Instituto de Química, Caixa Postal 68563, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-909, Brazil. Tel.: + 55 21 2562 73 65; fax: + 55 21 2562 72 66; e-mail: monica@iq.ufrj.br

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Abstract

Re-emergence of vector-borne diseases such as dengue and yellow fever, which are both transmitted by the Aedes aegypti mosquito, has been correlated with insecticide resistance. P-glycoproteins (P-gps) are ATP-dependent efflux pumps that are involved in the transport of substrates across membranes. Some of these proteins have been implicated in multidrug resistance (MDR). In this study, we identified a putative P-glycoprotein in the Ae. aegypti database based on its significantly high identity with Anopheles gambiae, Culex quinquefasciatus, Drosophila melanogaster and human P-gps. The basal ATPase activity of ATP-binding cassette transporters in larvae was significantly increased in the presence of MDR modulators (verapamil and quinidine). An eightfold increase in Ae. aegypti P-gp (AaegP-gp) gene expression was detected in temephos-treated larvae as determined by quantitative PCR. To analyse the potential role of AaegP-gp in insecticide efflux, a temephos larvicide assay was performed in the presence of verapamil. The results showed an increase of 24% in temephos toxicity, which is in agreement with the efflux reversing effect. RNA interference (RNAi)-mediated silencing of the AaegP-gp gene caused a significant increase in temephos toxicity (57%). In conclusion, we have demonstrated for the first time in insects that insecticide-induced P-gp expression can be involved in the modulation of insecticide efflux.

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