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Insect Mol Biol. 2013 Dec;22(6):648-58. doi: 10.1111/imb.12052. Epub 2013 Aug 27.

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

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Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, RJ, Brazil; Universidade Federal do Rio de Janeiro, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Rio de Janeiro, RJ, Brazil.


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.


Aedes aegypti; MDR modulators; P-glycoprotein; RNA interference (RNAi); insecticide efflux; temephos

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