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

• Published in: Insect molecular biology 2013-12, Vol.22 (6), p.648-658
• Main Authors: Figueira-Mansur, J., Ferreira-Pereira, A., Mansur, J. F., Franco, T. A., Alvarenga, E. S. L., Sorgine, M. H. F., Neves, B. C., Melo, A. C. A., Leal, W. S., Masuda, H., Moreira, M. F.
• Format: Article
• Language: English
• Subjects: Aedes - drug effects; Aedes aegypti; Amino Acid Sequence; Animals; Anopheles gambiae; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette Transporters - metabolism; Culex quinquefasciatus; Drosophila melanogaster; Gene Expression - drug effects; insecticide efflux; Insecticide Resistance - genetics; Larva - drug effects; MDR modulators; Molecular Sequence Data; Mortality; P-glycoprotein; Quinidine - pharmacology; RNA interference (RNAi); Temefos; temephos; Verapamil - pharmacology
• ISSN: 0962-1075; 1365-2583
• DOI: 10.1111/imb.12052

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.