In this study, we investigated whether the optimization of dose, the timing of exposure, and the assessment of transcript levels during tolerance can be used to identify detoxification genes that metabolize ivermectin (IVM). Using a non-invasive induction assay (brief exposure to sub-lethal levels of IVM administered in a stress reducing fashion) and qPCR, our transcriptional profiling results identified IVM-induced detoxification genes. CYP6CJ1, CYP9AG1, CYP9AG2, and phABCC4 were most significantly induced, had high basal expression levels, and were most closely related to genes from other organisms that metabolized insecticides, including IVM. Lice injected with dsRNAs against either CYP9AG2 or PhABCC4 exhibited significant reduction of their respective transcript level and showed increased IVM sensitivity, indicating that CYP9AG2 and phABCC4 are involved in the IVM metabolism and in the production of tolerance. Functional expression of these candidate genes will establish the actual metabolism of ivermectin and identify the metabolites formed.

Brief exposure of human body and head lice to sub-lethal amounts of ivermectin over transcribes detoxification genes involved in tolerance

244th National Meeting (2012)

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