Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Comparative Transcriptomic Analysis of Insecticide Resistant Aedes aegypti from Puerto Rico Reveals Insecticide-Specific Patterns of Gene Expression

Version 1 : Received: 10 July 2023 / Approved: 11 July 2023 / Online: 12 July 2023 (07:55:39 CEST)

A peer-reviewed article of this Preprint also exists.

Derilus, D.; Impoinvil, L.M.; Muturi, E.J.; McAllister, J.; Kenney, J.; Massey, S.E.; Hemme, R.; Kothera, L.; Lenhart, A. Comparative Transcriptomic Analysis of Insecticide-Resistant Aedes aegypti from Puerto Rico Reveals Insecticide-Specific Patterns of Gene Expression. Genes 2023, 14, 1626. Derilus, D.; Impoinvil, L.M.; Muturi, E.J.; McAllister, J.; Kenney, J.; Massey, S.E.; Hemme, R.; Kothera, L.; Lenhart, A. Comparative Transcriptomic Analysis of Insecticide-Resistant Aedes aegypti from Puerto Rico Reveals Insecticide-Specific Patterns of Gene Expression. Genes 2023, 14, 1626.

Abstract

Aedes aegypti transmits major arboviruses of public health importance, including dengue, chikungunya, Zika, and yellow fever. The use of insecticides represents the cornerstone of vector control, however insecticide resistance in Ae. aegypti has become widespread. Understanding the molecular basis of insecticide resistance in this species is crucial to design effective resistance management strategies. Here, we applied Illumina RNA-Seq to study the gene expression patterns associated with resistance to three widely used insecticides (malathion, alpha-cypermethrin and lambda-cyhalothrin) in Ae. aegypti populations from 2 sites (Manatí and Isabela) in Puerto Rico (PR). Cytochrome P450s were the most over-expressed detoxification genes across all resistant phenotypes. Some detoxification genes (CYP6Z7, CYP28A5, CYP9J2, CYP6Z6, CYP6BB2, CYP6M9, and two CYP9F2 orthologs) were commonly over-expressed in mosquitoes that survived exposure to all three insecticides (independent of geographical origin) while others including CYP6BY1 (malathion), GSTD1 (alpha-cypermethrin), CYP4H29 and GSTE6 (lambda-cyhalothrin) were uniquely overexpressed in mosquitoes that survived exposure to specific insecticides. The gene ontology (GO) terms associated with monooxygenase, iron binding, and passive transmembrane transporter activities were significantly enriched in 4 out of 6 resistant vs susceptible comparisons while serine protease activity was elevated in all insecticide resistant groups relative to the susceptible strain. Interestingly, cuticular-related protein genes (chinase and chitin) were predominantly downregulated, which was also confirmed in the functional enrichment analysis. This RNA-Seq analysis presents a detailed picture of the candidate detoxification genes and other pathways that are potentially associated with pyrethroid and organophosphate resistance in Ae. aegypti populations from PR. These results could inform development of novel molecular tools for detection of resistance-associated gene expression in this important arbovirus vector and guide the design and implementation of resistance management strategies.

Keywords

Aedes aegypti; insecticide resistance; RNA-Seq; detoxification genes; mosquitoes; Puerto Rico; organophosphate resistance; pyrethroid resistance

Subject

Biology and Life Sciences, Insect Science

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