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PLoS One ; 8(4): e61408, 2013.
Article in English | MEDLINE | ID: mdl-23626680

ABSTRACT

BACKGROUND: In the city of Yaoundé in Cameroon malaria is predominately transmitted by the M and S molecular forms of Anopheles gambiae and both are resistant to the pyrethroid insecticides and DDT. Mutations in the target site of these insecticides, present at a high frequency in malaria vectors in this city, contribute to this resistance profile. To identify additional resistance mechanisms, the expression profile of multiple DDT-resistant field populations of M and S molecular forms was compared to laboratory-susceptible populations. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of DDT resistance was highest in the S form population originating from the cultivated site of Nkolondom (mortality after WHO bioassay = 4%). A high prevalence of DDT resistance was also found in two urban M form populations, Messa from a pristine unpolluted environment (DDT mortality = 54%), and Gare, where the breeding sites are heavily polluted with organic matter (DDT mortality = 38%). Microarray analysis showed that several transcripts coding for detoxification enzymes (P450s, GSTs and UDPGTs) and ABC transporters were upregulated in the three populations. Despite the presence of multiple detoxification genes over expressed in the DDT-resistant subset of these field populations, only three were commonly over expressed in resistant populations from all three environments. Two of these genes, CYP6M2 and GSTD1-6, encode enzymes that have been previously shown to metabolize DDT. CONCLUSION/SIGNIFICANCE: Analogous to target site resistance, genes involved in metabolic resistance to DDT are also shared between the M and S forms of An gambiae. Alternative explanations for this occurrence are explored.


Subject(s)
Anopheles/genetics , Gene Expression Regulation , Inactivation, Metabolic/genetics , Insect Proteins/genetics , Insecticide Resistance/genetics , Insecticides/pharmacology , ATP-Binding Cassette Transporters/genetics , Animals , Anopheles/classification , Cameroon , Cytochrome P-450 Enzyme System/genetics , DDT/metabolism , DDT/pharmacology , Gene Expression Profiling , Gene Frequency , Genotype , Glucuronosyltransferase/genetics , Glutathione Transferase/genetics , Insecticide Resistance/drug effects , Insecticides/metabolism , Oligonucleotide Array Sequence Analysis , Pyrethrins/metabolism , Pyrethrins/pharmacology , Urban Health
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