Genome-wide Search for Gene Mutations likely Conferring Insecticide Resistance in the Common Bed Bug, Cimex lectularius

Insecticide resistance in the bedbug Cimex lectularius is poorly understood due to the lack of genome sequences for resistant strains. In Japan, we identified a resistant strain of C. lectularius that exhibits a higher pyrethroid resistance ratio compared to many previously discovered strains. We sequenced genomes of the pyrethroid resistant and susceptible strains using long-read sequencing, resulting in the construction of highly contiguous genomes (N50 of resistant strain: 2.1Mb and N50 of susceptible strain: 1.5 Mb). Gene prediction was performed by BRAKER3 and Functional annotation was performed by Fanflow4insects workflow. Next, we compared their amino acid sequences to identify gene mutations, identifying 729 mutated transcripts that were specific to the resistant strain. Among them, those defined previously as resistance genes were included. Additionally, enrichment analysis implicated DNA damage response, cell cycle regulation, insulin metabolism, and lysosomes in the development of pyrethroid resistance. Genome editing of these genes can provide insights into the evolution and mechanisms of insecticide resistance. This study expanded the target genes to monitor allele distribution and frequency changes, which will likely contribute to the assessment of resistance levels. These findings highlight the potential of genome-wide approaches to understand insecticide resistance in bed bugs. Simple SummaryBedbugs have expanded globally over the past two decades, causing several health risks. Mutations in their genes allow bed bugs to develop insecticide resistance. However, the extent to which gene mutations exist in the bug genome remains largely unknown because the genomes of resistant strains have not been determined. We accurately sequenced the genomes of both susceptible and resistant strains and compared the gene sequences between the two strains. Several genes with resistance-specific mutations have been identified. These mutations can alter gene function and lead to insecticide resistance.