title: Silencing of P-glycoprotein increases mortality in temephos-treated Aedes aegypti larvae.
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.
authors: 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.
authors: J
authors: J
authors: Figueira-Mansur
authors: A
authors: A
authors: Ferreira-Pereira
authors: J F
authors: JF
authors: Mansur
authors: T A
authors: TA
authors: Franco
authors: E S L
authors: ES
authors: Alvarenga
authors: M H F
authors: MH
authors: Sorgine
authors: B C
authors: BC
authors: Neves
authors: A C A
authors: AC
authors: Melo
authors: W S
authors: WS
authors: Leal
authors: H
authors: H
authors: Masuda
authors: M F
authors: MF
authors: Moreira
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000330:Aedes / Q000187:drug effects*; D000595:Amino Acid Sequence; D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D007305:Insecticide Resistance / Q000235:genetics; D007814:Larva / Q000187:drug effects*; D008969:Molecular Sequence Data; D009026:Mortality; D011802:Quinidine / Q000494:pharmacology; D000002:Temefos; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D014700:Verapamil; D011802:Quinidine; D000002:Temefos
keywords: Aedes aegypti; MDR modulators; P-glycoprotein; RNA interference (RNAi); insecticide efflux; temephos