Abstract
Aedes aegypti is an important vector of human viral diseases. This mosquito is distributed globally and thrives in urban environments, making it a serious risk to human health. Pyrethroid insecticides have been the mainstay for control of adult A. aegypti for decades, but resistance has evolved, making control problematic in some areas. One major mechanism of pyrethroid resistance is detoxification by cytochrome P450 monooxygenases (CYPs), commonly associated with the overexpression of one or more CYPs. Unfortunately, the molecular basis underlying this mechanism remains unknown. We used a combination of RNA-seq and proteomic analysis to evaluate the molecular basis of pyrethroid resistance in the highly resistant CKR strain of A. aegypti. The CKR strain has the resistance mechanisms from the well-studied Singapore (SP) strain introgressed into the susceptible Rockefeller (ROCK) strain genome. The RNA-seq and proteomics data were complimentary; each offering insights that the other technique did not provide. However, transcriptomic results did not quantitatively mirror results of the proteomics.There were 10 CYPs which had increased expression of both transcripts and proteins. These CYPs appeared to be largely trans-regulated, except for some CYPs for which we could not rule out gene duplication. We identified 65 genes and lncRNAs as potentially being responsible for elevating the expression of CYPs in CKR. Resistance was associated with multiple loci on chromosome 1 and at least one locus on chromosome 3. We also identified five CYPs that were overexpressed only as proteins, suggesting that stabilization of CYP proteins could be a mechanism of resistance. Future studies to increase the resolution of the resistance loci, and to examine the candidate genes and lncRNAs identified here will greatly enhance our understanding of CYP-mediated resistance in A. aegypti.
Highlights
Aedes aegypti vectors four important human disease viruses: dengue, yellow fever, Zika and chikungunya
We identified cytochrome P450 monooxygenases (CYPs) that were overexpressed in the CKR strain, and for most of these the increased expression was due to a trans-acting factor
The goals of this study were to 1) use transcriptomics (RNA-seq) and proteomics to improve our understanding of the molecular basis of CYPmediated resistance in A. aegypti, and 2) to determine if the levels of CYP transcripts correlate with levels of CYP proteins across strains
Summary
Aedes aegypti vectors four important human disease viruses: dengue, yellow fever, Zika and chikungunya. Dengue, the most devastating virus vectored by A. aegypti, is estimated to be a risk to over 50% of the world’s population [2], and Zika has generated a great deal of human health concern since it arrived in the Americas in 2014 [3,4,5,6,7]. Due to their efficacy and fast action, the use of insecticides has often been the only feasible control strategy for vector-borne diseases. Identification of the mutations responsible for resistance is a necessary first step for the development of sensitive, high-throughput assays for resistance detection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
