title: High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes.
abstract: We investigated the genetic determinism of high chlorpyrifos resistance (HCR), a phenotype first described in 1999 in Culex pipiens mosquitoes surviving chlorpyrifos doses ⩾1 mg l(-1) and more recently found in field samples from Tunisia, Israel or Indian Ocean islands. Through chlorpyrifos selection, we selected several HCR strains that displayed over 10 000-fold resistance. All strains were homozygous for resistant alleles at two main loci: the ace-1 gene, with the resistant ace-1(R) allele expressing the insensitive G119S acetylcholinesterase, and a resistant allele of an unknown gene (named T) linked to the sex and ace-2 genes. We constructed a strain carrying only the T-resistant allele and studied its resistance characteristics. By crossing this strain with strains harboring different alleles at the ace-1 locus, we showed that the resistant ace-1(R) and the T alleles act in strong synergy, as they elicited a resistance 100 times higher than expected from a simple multiplicative effect. This effect was specific to chlorpyrifos and parathion and was not affected by synergists. We also examined how HCR was expressed in strains carrying other ace-1-resistant alleles, such as ace-1(V) or the duplicated ace-1(D) allele, currently spreading worldwide. We identified two major parameters that influenced the level of resistance: the number and the nature of the ace-1-resistant alleles and the number of T alleles. Our data fit a model that predicts that the T allele acts by decreasing chlorpyrifos concentration in the compartment targeted in insects.
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.|Arthropod-Borne and Infectious Diseases Laboratory, Colorado State University, Fort Collins, CO, USA.
authors.forename: H
authors.initials: H
authors.lastname: Alout
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Labbé
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Berthomieu
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Makoundou
authors.affiliation: University of Montpellier, Montpellier, France.|CNRS, CRBM-UMR, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Fort
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Pasteur
authors.affiliation: CNRS, IRD, ISEM-UMR, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Weill
mesh_terms: D000110:Acetylcholinesterase; D000483:Alleles; D000818:Animals; D004390:Chlorpyrifos; D003433:Crosses, Genetic; D003465:Culex / Q000235:genetics*; D005260:Female; D017344:Genes, Insect; D008040:Genetic Linkage; D005828:Genetics, Population; D019156:Indian Ocean; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides; D007557:Israel; D008297:Male; D012744:Sex Ratio; D014416:Tunisia
chemical_list: D007306:Insecticides; D000110:Acetylcholinesterase; D004390:Chlorpyrifos