Unraveling the mystery of spinosad resistance in insects

Spinosad (a mixture of spinosyns A and D, Fig. 1) is a new and highly promising insecticide, derived from the bacteria Saccharopolyspora spinosa, with efficacy against a wide range of insects. The mechanism of action of spinosad appears to be unique, with a primary site of attack being the nicotinic acetylcholine receptor (nAChR) and a secondary site of attack being g-aminobutyric acid (GABA) receptors. Spinosad is thought to exert its toxicity primarily by activating a nAChR (nAChN subtype). Studies showing that deletion of the Da6 nAChR results in strains of Drosophila melanogaster that are highly resistant to spinosad confirms the importance of nAChRs in spinosad toxicity. This unique mechanism(s) of action suggests that resistance due to changes in the target sites of other major insecticides (i.e. acetylcholinesterase and voltage sensitive sodium channel) would not result in cross-resistance to spinosad. This appears true for house flies and the oriental fruit fly (Bactrocera dorsalis) where only modest levels of cross-resistance to spinosad have been observed in laboratory strains and in field collected populations. However, strains of Bactrocera dorsalis selected for resistance to organophosphates, carbamates or pyrethroids mechanisms unknown were up to 1000-fold cross-resistant to spinosad.