Liu_2026_Curr.Opin.Insect.Sci__101510

The house fly (Musca domestica) is a globally important pest that affects human and livestock health and contributes to significant economic losses in animal-production systems. Intensive and prolonged insecticide use has led to rapid, recurrent resistance across nearly all major chemical classes. This review synthesizes recent advances in understanding the molecular basis of metabolic resistance in M. domestica, emphasizing four detoxification enzyme families: cytochrome P450s, carboxylesterases, glutathione S-transferases, and UDP-glucuronosyltransferases. Key genes, including CYP6A1, CYP6D1, CYP6G4, and MdalphaE7, illustrate the polygenic and interconnected nature of detoxification pathways. Chromosomal mapping highlights both cis- and trans-regulatory mechanisms, with autosome 2 emerging as a central regulatory hub. Recent studies further identify G protein-coupled receptor (GPCR) signaling as an upstream modulator of resistance, where rhodopsin-like GPCR overexpression elevates resistance levels and P450 expression. Additionally, a CYP6G4 allele containing a CncC/Maf binding-site insertion connects GPCR signaling to oxidative-stress pathways, contributing to multi-insecticide resistance.