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 [1]. 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 of the major mechanisms of pyrethroid resistance is detoxification by cytochrome P450 monooxygenases (CYPs), commonly associated with the overexpression of one or more CYPs. Unfortunately, the molecular basis underling this mechanism remains a mystery. We used a combination of RNA-Seq and proteomic analysis to evaluate the molecular basis of pyrethroid resistance in the highly resistant Singapore (SP) strain. A strain that is congenic to the susceptible ROCK strain, but has the SP resistance mechanisms introgressed into the genome was also used to improve the detection of resistance associated traits. The RNA-Seq and proteomics data were complimentary; each offering insights that the other technique did not provide. However, use of transcriptomics did not quantitatively mirror the 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 were able to identify &lt;30 genes and lncRNAs as having the potential for being responsible for elevating the expression of CYPs in SP. Resistance was associated with multiple loci and chromosome 1 and at least on locus on chromosome 3. 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.

Transcriptomic and proteomic analysis of pyrethroid resistance in the Singapore strain of Aedes aegypti

ACS Fall 2021

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