title: Carbamate and pyrethroid resistance in the akron strain of Anopheles gambiae.
abstract: Insecticide resistance in the malaria vector, Anopheles gambiae, is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a "pseudo-pyrethroid." There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety.
authors.affiliation: Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Mutunga
authors.affiliation: Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Anderson
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Craft
authors.affiliation: Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gross
authors.affiliation: Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Swale
authors.affiliation: Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Tong
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Wong
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Carlier
authors.affiliation: Emerging Pathogens Institute, Department of Entomology and Nematology, University of Florida, Gainesville, FL 32610, USA. Electronic address: jbquist@epi.ufl.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bloomquist
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000201:enzymology; D002219:Carbamates / Q000494:pharmacology*; D003634:DDT / Q000494:pharmacology*; D004950:Esterases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007305:Insecticide Resistance / Q000502:physiology; D007306:Insecticides / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D002219:Carbamates; D007306:Insecticides; D011722:Pyrethrins; D003634:DDT; D005982:Glutathione Transferase; D004950:Esterases; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Anticholinesterase; Knockdown resistance; Metabolic resistance; Mosquito