Cytochrome P450 monooxygenase-mediated permethrin resistance confers limited and larval specific cross-resistance in the southern house mosquito, Culex pipiens quinquefasciatus

Hardstone, Melissa C.; Leichter, Cheryl A.; Harrington, Laura C.; Kasai, Shinji; Tomita, Takashi; Scott, Jeffrey G.

doi:10.1016/j.pestbp.2007.06.006

Cited by 60 publications

(69 citation statements)

References 39 publications

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“…The evidence for in vitro metabolism and up-regulation presented here (see also Komagata et al, 2010), implicate CYP9M10 as a causal gene underlying resistance in lab strains. CYP4H34 does not metabolise deltamethrin and CYP9M10 displays only very weak activity, correlating with the known phenotypic resistance profile of the ISOP450 strain (Hardstone et al, 2007). Differential metabolism of class I and class II pyrethroids has been seen for other CYP450s e.g.…”

Section: Discussionmentioning

confidence: 61%

“…The ISOP450 strain of Culex quinquefasciatus was supplied by Dr J. Scott (Cornell University) and exhibits larval resistance to permethrin (Hardstone et al, 2007 , 2005). Briefly, batches of 25 larvae were exposed to permethrin concentrations (ranging from 0.0001 to 10ppm) in 100ml water and mortality determined after 24 hrs.…”

Section: Strains Of CX Quinquefasciatus Usedmentioning

confidence: 99%

“…To address this, Hardstone et al (2007) developed the ISOP450 strain of Cx. quinquefasciatus through back-crossing JPAL to the standard susceptible S-LAB strain and selecting larvae at the L4 stage with permethrin, so embedding the pyrethroid resistance locus or loci in the S-LAB genetic background.…”

Section: Introductionmentioning

confidence: 99%

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A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: Functional characterisation and signatures of selection

Wilding

Smith

Lynd

et al. 2012

Insect Biochemistry and Molecular Biology

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Although cytochrome P450 (CYP450) enzymes are frequently up-regulated in mosquitoes resistant to insecticides, no regulatory motifs driving these expression differences with relevance to wild populations have been identified. Transposable elements (TEs) are often enriched upstream of those CYP450s involved in insecticide resistance, leading to the assumption that they contribute regulatory motifs that directly underlie the resistance phenotype. A partial CuRE1 (Culex Repetitive Element 1) transposable element is found directly upstream of CYP9M10, a cytochrome P450 implicated previously in larval resistance to permethrin in the ISOP450 strain of Cx. quinquefasciatus, but is absent from the equivalent genomic region of a susceptible strain. Via expression of CYP9M10 in E.coli we have now demonstrated time-and NADPH-dependant permethrin metabolism, prerequisites for confirmation of a role in metabolic resistance, and through qPCR shown that CYP9M10 is >20-fold over-expressed in ISOP450 compared to a susceptible strain. In a fluorescent reporter assay the region upstream of CYP9M10 from ISOP450 drove 10x expression compared to the equivalent region (lacking CuRE1) from the susceptible strain. Close correspondence with the gene expression fold-change implicates the upstream region including CuRE1 as a cis-regulatory element involved in resistance. Only a single CuRE1 bearing allele, identical to the CuRE1 bearing allele in the resistant strain, is found throughout Sub-Saharan Africa, in contrast to the diversity encountered in non-CuRE1 alleles. This suggests a single origin and subsequent spread due to selective advantage. CuRE1 is detectable using a simple diagnostic. When applied to Cx. quinquefasciatus larvae from Ghana we have demonstrated a significant association with permethrin resistance in multiple field sites (mean Odds Ratio = 3.86) suggesting this marker has relevance to natural populations of vector mosquitoes. However, when CuRE1 was excised from the allele used in the reporter assay through fusion PCR, expression was unaffected, indicating that the TE has no direct role in resistance and hence that CuRE1 is acting only as a marker of an as yet unidentified regulatory motif in the association analysis. This suggests that a re-evaluation of the assumption that TEs contribute regulatory motifs involved in gene expression may be necessary. 3 IntroductionThe control of a number of pernicious mosquito-borne diseases such as malaria, lymphatic filariasis Chanda et al., 2011;Himeidan et al., 2011; Mathias et al., 2011; Yewhalaw et al., 2011). Given that many resistance mutations are thought to be recessive in expression, development of DNA diagnostics enables disease and agricultural control programmes to identify resistance mechanisms when they are at low frequency and take ameliorating action before they cause economic or health impacts (Hemingway, 2009;Kelly-Hope et al., 2008). As shown in a number of recent studies, resistance alleles can rise towards fixation very rapidly (García et al., 2009;L...

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Section: Discussionmentioning

confidence: 61%

Section: Strains Of CX Quinquefasciatus Usedmentioning

confidence: 99%

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A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: Functional characterisation and signatures of selection

Wilding

Smith

Lynd

et al. 2012

Insect Biochemistry and Molecular Biology

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“…Laboratory assays have shown the involvement of G6PD and monooxygenases in deltamethrin-resistant mosquitoes (Kumar et al 1991;Ganesh et al 2002). Of late, investigations on pyrethroid resistance in A. aegypti (Yaicharoen et al 2005), A. aegypti and A. albopictus (Pethuan et al 2007), and C. quinquefasciatus (Hardstone et al 2007) has been attributed to the involvement of monooxygenases.…”

Section: Resultsmentioning

confidence: 99%

Biochemical characterization of deltamethrin resistance in a laboratory-selected strain of Aedes aegypti

Jagadeshwaran

Vijayan

2009

Parasitol Res

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A resistant strain (DR) of Aedes aegypti, generated by deltamethrin selection for 20 consecutive generations from a laboratory susceptible strain (DS) was studied for the possible resistant mechanisms. The pyrethroid resistance developed was characterized by biochemical assays and native polyacrylamide gel electrophoresis. Significant elevation in the activity of alpha- and beta-esterases, glucose-6-phosphate dehydrogenase (G6PD), CYTP450 (CYTP450), and glutathione-s-transferase (GST) were noticed in DR. The gel profiles for esterases, G6PD, and CYTP450 were different in DR as compared to DS strain. The difference was either in the form of additional bands or increased intensity of the bands or both. Gel profile variations were also evident from densitometry. Our study suggests that these enzymes play an important role in deltamethrin resistance in the DR strain.

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“…Pyrethroid insecticides are usually used to combat adult mosquitoes in the field. However, the resistance associated with the D-Cu( þ ) and Cu( þ ) haplotypes decreases markedly in the adult stage, because the overexpression of CYP9M10 almost halts after the larval stage (Hardstone et al, 2007;Komagata et al, 2010;Li and Liu, 2010;Itokawa et al, 2011). Although nontargeted organisms, such as Drosophila (Catania et al, 2004;Schlenke and Begun, 2004), could be subject to selective pressure of insecticides, perhaps as off-target victims of agricultural pesticide usage (Antonio-Nkondjio et al, 2011), it is unclear how often in the field C. quinquefasciatus encounters aquatic environments with high pyrethroid concentrations, where the D-Cu( þ ) haplotype is advantageous over Cu( þ ) haplotypes.…”

Section: Discussionmentioning

confidence: 99%

Global spread and genetic variants of the two CYP9M10 haplotype forms associated with insecticide resistance in Culex quinquefasciatus Say

et al. 2013

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Insecticide resistance develops as a genetic factor (allele) conferring lower susceptibility to insecticides proliferates within a target insect population under strong positive selection. Intriguingly, a resistance allele pre-existing in a population often bears a series of further adaptive allelic variants through new mutations. This phenomenon occasionally results in replacement of the predominating resistance allele by fitter new derivatives, and consequently, development of greater resistance at the population level. The overexpression of the cytochrome P450 gene CYP9M10 is associated with pyrethroid resistance in the southern house mosquito Culex quinquefasciatus. Previously, we have found two genealogically related overexpressing CYP9M10 haplotypes, which differ in gene copy number (duplicated and non-duplicated). The duplicated haplotype was derived from the non-duplicated overproducer probably recently. In the present study, we investigated allelic series of CYP9M10 involved in three C. quinquefasciatus laboratory colonies recently collected from three different localities. Duplicated and non-duplicated overproducing haplotypes coexisted in African and Asian colonies indicating a global distribution of both haplotype lineages. The duplicated haplotypes both in the Asian and African colonies were associated with higher expression levels and stronger resistance than non-duplicated overproducing haplotypes. There were slight variation in expression level among the nonduplicated overproducing haplotypes. The nucleotide sequences in coding and upstream regions among members of this group also showed a little diversity. Non-duplicated overproducing haplotypes with relatively higher expression were genealogically closer to the duplicated haplotypes than the other non-duplicated overproducing haplotypes, suggesting multiple cis-acting mutations before duplication.

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Cytochrome P450 monooxygenase-mediated permethrin resistance confers limited and larval specific cross-resistance in the southern house mosquito, Culex pipiens quinquefasciatus

Cited by 60 publications

References 39 publications

A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: Functional characterisation and signatures of selection

A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: Functional characterisation and signatures of selection

Biochemical characterization of deltamethrin resistance in a laboratory-selected strain of Aedes aegypti

Global spread and genetic variants of the two CYP9M10 haplotype forms associated with insecticide resistance in Culex quinquefasciatus Say

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