Dataset Information

Mechanisms of pyrethroid resistance in Aedes (Stegomyia) aegypti from Colombia.

ABSTRACT: In Colombia Aedes (Stegomyia) aegypti is the main vector of urban arboviruses such as dengue, chikungunya and Zika. This urban mosquito has a well-established capacity to develop insecticide resistance to different types of insecticides (pyrethroids, organochlorides, organophosphates), using multiple resistance mechanisms. An understanding of ongoing resistance mechanisms is critical to determining the activities of vector control programs. In order to identify the biochemical and molecular mechanisms associated with pyrethroid resistance in Colombia, three laboratory-selected strains resistant to DDT, Propoxur and lambdacyhalothrin, and 7 field-collected strains were evaluated. CDC bioassays were performed to measure the susceptibility status to pyrethroid type I (permethrin) and II (deltamethrin and lambdacyhalothrin), and potential cross-resistance to different types of insecticides; organochlorine (DDT), carbamates (propoxur) and organophosphates (malathion). The enzymatic activity of esterases, glutathione S-transferases (GST) and P450 monooxygenases were biochemically determined. Frequencies of kdr mutations Val1016Ile and Phe1534cys were determined through real-time PCR. The Rockefeller strain of Aedes (Stegomyia) aegypti was used as the susceptible control. The laboratory-selected strains "propoxur" and "lambdacyhalothrin" and one field population (Medellín (BF) F2 were resistant to all evaluated pyrethroids. Six of the seven field populations as well as the laboratory- selected "DDT" strain were resistant to permethrin. All the evaluated strains were resistant to DDT. Cross-resistance between lambdacyhalothrin and propoxur was observed in the laboratory-selected strains; however, all field-collected strains were susceptible to propoxur and no evidence of malathion resistance was found. The main biochemical mechanism for resistance observed in the field-collected strains was related to the enzyme GST. Further, the frequencies of kdr mutations alleles associated with insecticide resistance were high and ranged from 0.02 to 0.72 for Ile1016 and from 0.44 to 0.99 for Cys1534. Strains with high frequencies of both kdr mutations were resistant to both type I and II pyrethroids. These results suggest that Ae. aegypti from Colombia have developed multiple resistance mechanisms associated with pyrethroid resistance; therefore a resistance management strategy against these field populations of Ae. Aegypti, incorporating these findings is strongly recommended.

SUBMITTER: Aponte A

PROVIDER: S-EPMC6447284 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Mechanisms of pyrethroid resistance in Aedes (Stegomyia) aegypti from Colombia.

Aponte Angélica A Penilla R Patricia RP Rodríguez Américo D AD Ocampo Clara B CB

Acta tropica 20181212

In Colombia Aedes (Stegomyia) aegypti is the main vector of urban arboviruses such as dengue, chikungunya and Zika. This urban mosquito has a well-established capacity to develop insecticide resistance to different types of insecticides (pyrethroids, organochlorides, organophosphates), using multiple resistance mechanisms. An understanding of ongoing resistance mechanisms is critical to determining the activities of vector control programs. In order to identify the biochemical and molecular mech ...[more]

PMID: 30552882

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Project description:BackgroundAedes aegypti is an important vector of many human diseases and a serious threat to human health due to its wide geographic distribution and preference for human hosts. A. aegypti also has evolved widespread resistance to pyrethroids due to the extensive use of this insecticide class over the past decades. Mutations that cause insecticide resistance result in fitness costs in the absence of insecticides. The fitness costs of pyrethroid resistance mutations in A. aegypti are still poorly understood despite their implications for arbovirus transmission.Methodology/principle findingsWe evaluated fitness based both on allele-competition and by measuring specific fitness components (i.e. life table and mating competition) to determine the costs of the different resistance mechanisms individually and in combination. We used four congenic A. aegypti strains: Rockefeller (ROCK) is susceptible to insecticides; KDR:ROCK (KR) contains only voltage-sensitive sodium channel (Vssc) mutations S989P+V1016G (kdr); CYP:ROCK (CR) contains only CYP-mediated resistance; and CYP+KDR:ROCK (CKR) contains both CYP-mediated resistance and kdr. The kdr allele frequency decreased over nine generations in the allele-competition study regardless of the presence of CYP-mediated resistance. Specific fitness costs were variable by strain and component measured. CR and CKR had a lower net reproductive rate (R0) than ROCK or KR, and KR was not different than ROCK. There was no correlation between the level of permethrin resistance conferred by the different mechanisms and their fitness cost ratio. We also found that CKR males had a reduced mating success relative to ROCK males when attempting to mate with ROCK females.Conclusions/significanceBoth kdr and CYP-mediated resistance have a fitness cost affecting different physiological aspects of the mosquito. CYP-mediated resistance negatively affected adult longevity and mating competition, whereas the specific fitness costs of kdr remains elusive. Understanding fitness costs helps us determine whether and how quickly resistance will be lost after pesticide application has ceased.

Project description:Association mapping of factors that condition pyrethroid resistance in Aedes aegypti has consistently identified genes in multiple functional groups. Toward better understanding of the mechanisms involved, we examined high throughput sequencing data (HTS) from two Aedes aegypti aegypti collections from Merida, Yucatan, Mexico treated with either permethrin or deltamethrin. Exome capture enrichment for coding regions and the AaegL5 annotation were used to identify genes statistically associated with resistance. The frequencies of single nucleotide polymorphisms (SNPs) were compared between resistant and susceptible mosquito pools using a contingency ?2 analysis. The -log10(?2 p value) was calculated at each SNP site, with a weighted average determined from all sites in each gene. Genes with -log10(?2 p value) ? 4.0 and present among all 3 treatment groups were subjected to gene set enrichment analysis (GSEA). We found that several functional groups were enriched compared to all coding genes. These categories were transport, signal transduction and metabolism, in order from highest to lowest statistical significance. Strikingly, 21 genes with demonstrated association to synaptic function were identified. In the high association group (n = 1,053 genes), several genes were identified that also genetically or physically interact with the voltage-gated sodium channel (VGSC). These genes were eg., CHARLATAN (CHL), a transcriptional regulator, several ankyrin-domain proteins, PUMILIO (PUM), a translational repressor, and NEDD4 (E3 ubiquitin-protein ligase). There were 13 genes that ranked among the top 10%: these included VGSC; CINGULIN, a predicted neuronal gap junction protein, and the aedine ortholog of NERVY (NVY), a transcriptional regulator. Silencing of CHL and NVY followed by standard permethrin bottle bioassays validated their association with permethrin resistance. Importantly, VGSC levels were also reduced about 50% in chl- or nvy-dsRNA treated mosquitoes. These results are consistent with the contribution of a variety of neuronal pathways to pyrethroid resistance in Ae. aegypti.

Dataset Information

Mechanisms of pyrethroid resistance in Aedes (Stegomyia) aegypti from Colombia.

Publications

Mechanisms of pyrethroid resistance in Aedes (Stegomyia) aegypti from Colombia.

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