title: The Anopheles gambiae detoxification chip: a highly specific microarray to study metabolic-based insecticide resistance in malaria vectors.
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 230 Anopheles gambiae genes 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 susceptible An. gambiae laboratory strains. Five genes were strongly up-regulated in the dichlorodiphenyltrichloroethane-resistant strain ZAN/U. These genes included the GST GSTE2, which has previously been implicated in dichlorodiphenyltrichloroethane resistance, two P450s, and two peroxidase genes. GSTE2 was also elevated in the pyrethroid-resistant RSP strain. In addition, the P450 CYP325A3, 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.
authors.affiliation: Vector Research Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L35QA, United Kingdom.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: David
authors.forename: Clare
authors.initials: C
authors.lastname: Strode
authors.forename: John
authors.initials: J
authors.lastname: Vontas
authors.forename: Dimitra
authors.initials: D
authors.lastname: Nikou
authors.forename: Ashley
authors.initials: A
authors.lastname: Vaughan
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Pignatelli
authors.forename: Christos
authors.initials: C
authors.lastname: Louis
authors.forename: Janet
authors.initials: J
authors.lastname: Hemingway
authors.forename: Hilary
authors.initials: H
authors.lastname: Ranson
mesh_terms: D000852:Anopheles / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003634:DDT / Q000378:metabolism; D020869:Gene Expression Profiling; D007305:Insecticide Resistance / Q000235:genetics / Q000502:physiology; D007306:Insecticides / Q000378:metabolism; D008288:Malaria / Q000517:prevention & control / Q000635:transmission; D020411:Oligonucleotide Array Sequence Analysis; D026023:Permethrin / Q000378:metabolism
chemical_list: D007306:Insecticides; D026023:Permethrin; D003577:Cytochrome P-450 Enzyme System; D003634:DDT