Isolation and characterization of the decreased cuticular penetration mechanism of fluralaner resistance in the house fly, Musca domestica

Decreased cuticular penetration has been documented as a mechanism of resistance in several insects, yet this mechanism remains poorly understood. Levels of resistance conferred, effects of the physicochemical properties on the manifestation of resistance and the effects of different routes of exposure are largely unknown. We recently selected a strain (FlurR) of house fly that was >11,000-fold resistance to fluralaner, and decreased cuticular penetration was one of the mechanisms of resistance (Norris et al., 2023). We sought to isolate the decreased penetration mechanism from FlurR into the background of the susceptible aabys strain, and to characterize the protection it conferred to fluralaner and other insecticides. We successfully isolated the decreased penetration mechanism and found that it conferred 7.1-fold resistance to fluralaner, and 1.4- to 4.9-fold cross-resistance to five other insecticides by topical application. Neither mass, metabolic lability, vapor pressure, nor logP explained the differences in the resistance ratios. The mechanism also conferred cross resistance by residual and feeding exposure, although at reduced levels compared to topical application. Remaining data gaps in our understanding of this mechanism are discussed.