TheAnopheles gambiaedetoxification chip: A highly specific microarray to study metabolic-based insecticide resistance in malaria vectors

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Abstract
Metabolic pathways play an important role in insecticide resistance, but the full spectra of the genes involved in resistance has not been established. We constructed a microarray containing unique fragments from 230Anopheles gambiaegenes putatively involved in insecticide metabolism [cytochrome P450s (P450s), GSTs, and carboxylesterases and redox genes, partners of the P450 oxidative metabolic complex, and various controls]. We used this detox chip to monitor the expression of the detoxifying genes in insecticide resistant and susceptibleAn. gambiaelaboratory strains. Five genes were strongly up-regulated in the dichlorodiphenyltrichloroethane-resistant strainZAN/U. These genes included the GSTGSTE2, which has previously been implicated in dichlorodiphenyltrichloroethane resistance, two P450s, and two peroxidase genes.GSTE2was also elevated in the pyrethroid-resistantRSPstrain. In addition, the P450CYP325A3, belonging to a class not previously associated with insecticide resistance, was expressed at statistically higher levels in this strain. The applications of this detox chip and its potential contribution to malaria vector insecticide resistance management programs are discussed.

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