Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vectorCulex quinquefasciatus

ABSTRACT Culex quinquefasciatus plays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackle C. quinquefasciatus vectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, including C. quinquefasciatus . Herein, the transcriptome profile of Ugandan bendiocarb-resistant C. quinquefasciatus was explored to identify candidate genes associated with insecticide resistance. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1h exposure and 58.02% after 4h. Genotyping of the G119S Ace-1 target site mutation detected a highly significant association ( p <0.0001; OR=25) between resistance and Ace1 -119S. However, synergist assays using the P450 inhibitor PBO or the esterase inhibitor TPP resulted in markedly increased mortality (to ≈80%), suggesting a role of metabolic resistance in the resistance phenotype. Using a novel, custom 60K whole-transcriptome microarray 16 genes significantly overexpressed in resistant mosquitoes were detected, with the P450 Cyp6z18 showing the highest differential gene expression (>8-fold increase vs unexposed controls). These results provide evidence that bendiocarb-resistance in Ugandan C. quinquefasciatus is mediated by both target-site mechanisms and over-expression of detoxification enzymes.