An adult-specific CYP6 P450 gene is overexpressed in a pyrethroid-resistant strain of the malaria vector, Anopheles gambiae.
Many malaria control programmes are based on insecticide application as adulticides, often in the form of pyrethroid-impregnated bed nets. However, the efficacy of this control measure can be reduced by genetic changes in vector insecticide susceptibility. Pyrethroid resistance has been detected in the major African malaria vector, Anopheles gambiae, and has been attributed to a combination of target site insensitivity and increased oxidative metabolism of the insecticide, catalysed by cytochrome P450s. An adult-specific cytochrome P450 monooxygenase 6 (CYP6) P450 gene, CYP6Z1, located within a large cluster of cytochrome P450 genes in chromosome arm 3R of An. gambiae, is expressed approximately 11-fold higher in males and 4.5-fold in females from a pyrethroid-resistant strain than in a susceptible strain from the same geographical area. In both strains, CYP6Z1 expression is higher in males than females. Southern blot analysis discounted gene amplification as a cause of this overexpression. The isolation of An. gambiae cDNAs encoding cytochrome b(5) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH)-cytochrome P450 reductase cDNAs is also reported.
Nikou
Dimitra
D
Vector Biology Division, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Ranson
Hilary
H
Hemingway
Janet
J
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D002875:Chromosomes / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072472:Cytochrome P450 Family 6; D015786:Cytochromes b5 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D023061:Gene Order; D017344:Genes, Insect / Q000235:genetics; D019476:Insect Proteins; D007303:Insect Vectors / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology; D008288:Malaria / Q000635:transmission; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics; D011722:Pyrethrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D019476:Insect Proteins; D007306:Insecticides; D011722:Pyrethrins; D012333:RNA, Messenger; D004247:DNA; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C092307:CYP6D1 protein, Musca domestica; D000072472:Cytochrome P450 Family 6; D009251:NADPH-Ferrihemoprotein Reductase