期刊
INSECT MOLECULAR BIOLOGY
卷 22, 期 6, 页码 648-658出版社
WILEY
DOI: 10.1111/imb.12052
关键词
insecticide efflux; P-glycoprotein; temephos; Aedes aegypti; MDR modulators; RNA interference (RNAi)
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Instituto Nacional de Ciencia e Tecnologia em Entomologia Molecular (INCT-EM/CNPq),
- Ministerio da Saude
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- CoordenacAo de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- NSF [0918177]
- SDA-NIFA-AFRI [2010-65105-20582]
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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