# Comparative transcriptomics reveals different profiles between diflubenzuron‐resistant and ‐susceptible phenotypes of the mosquito Culex pipiens

## TL;DR

This study compares gene activity in mosquitoes resistant and susceptible to a pesticide, finding that resistant mosquitoes have higher activity in genes related to detoxification and cuticle formation.

## Contribution

The study identifies multiple gene expression changes in DFB-resistant mosquitoes, beyond the known target-site mechanism.

## Key findings

- 527 genes showed different activity levels between resistant and susceptible mosquitoes.
- Genes linked to detoxification and cuticle production were over-expressed in resistant mosquitoes.
- Cuticular protein transcripts were the most abundant among up-regulated genes.

## Abstract

Chitin‐synthesis inhibitors (CSIs) represent a major tool in vector control. The intensive use of these compounds has led to the evolution of resistance against several CSIs, including diflubenzuron (DFB). DFB resistance has been associated to a target‐site mechanism; however, studies investigating the gene expression profile of resistant phenotypes are limited, preventing a full understanding of DFB resistance. Here, we analyzed the constitutive gene expression of susceptible and DFB‐resistant individuals of the mosquito Culex pipiens, a major disease vector in temperate areas.

Comparative gene expression analysis between susceptible and DFB‐resistant individuals identified 527 differentially expressed genes (i.e., 432 up‐regulated and 95 down‐regulated genes). Among the up‐regulated genes, 87 genes belong to gene families associated with insecticide resistance in arthropods, such as cytochrome P450s, glutathione‐S‐transferases, UDP‐glucuronosyltransferases, heat shock proteins and cuticular proteins (CPs). Interestingly, the CP transcripts were the most abundant among up‐regulated genes (73 of 87), and furthermore they constitute 11 of the 20 most over expressed genes. The enrichment of transcripts associated with cuticle synthesis was also identified by the Gene Ontology (GO) enrichment analysis.

Adaptation to insecticides can involve transcriptional changes in genes encoding for multiple defense mechanisms. Our results identified the over‐expression of transcripts associated with detoxification and cuticle synthesis in DFB‐resistant individuals of Cx. pipiens. Multiple mechanisms, beyond the known target‐site mechanism, may therefore contribute to the DFB‐resistant phenotype. Together these findings corroborate the complexity underpinning the resistant phenotypes and provide important information for the implementation of effective control strategies against mosquito vectors. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Comparative gene expression analysis between susceptible and diflubenzuron‐resistant individuals of the mosquito Culex pipiens revealed transcriptional changes of multiple genes associated with insecticide detoxification and cuticle synthesis.