Identification, Validation, and Application of Molecular Diagnostics for Insecticide Resistance in Malaria Vectors

Donnelly, Martin J.; Isaacs, Alison T.; Weetman, David

doi:10.1016/j.pt.2015.12.001

Cited by 102 publications

(106 citation statements)

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“…The kdr mutations are highly related to PY resistance in several insect species, including vector mosquitoes, and have been therefore adopted as molecular markers for rapid screening of field populations [33, 59]. To our knowledge, we report here for the first time the Phe1534Cys substitution in the Na V of Ae.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: First report of the Phe1534Cyskdr mutation in natural populations of Aedes albopictusfrom Brazil

2017

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BackgroundKnockdown resistance (kdr), caused by alterations in the voltage-gated sodium channel (NaV), is one of the mechanisms responsible for pyrethroid (PY) resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different mutations were described in the IIIS6 NaV segment in populations from Asia, North America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6 NaV segments. The Phe1534Cys kdr mutation in the IIIS6 NaV segment is the most prevalent in populations of Ae. aegypti worldwide, also found in Ae. albopictus from Singapore. Herein, we investigated the DNA diversity corresponding to the IIS6 and IIIS6 NaV segments in natural populations of Ae. albopictus from Brazil.MethodsDNA from eight Brazilian Ae. albopictus natural populations were individually extracted and pooled by states of origin, amplified, cloned and sequenced for the corresponding IIS6 and IIIS6 NaV segments. Additionally, samples from each location were individually genotyped by an allelic specific PCR (AS-PCR) approach to obtain the genotypic and allelic frequencies for the 1534 NaV site.ResultsNo non-synonymous substitutions were observed in the IIS6 sequences. However, the Phe1534Cys kdr mutation was evidenced in the Ae. albopictus NaV IIIS6 segment sequences from Paraná (PR) and Rondônia (RO) states, but not from Mato Grosso (MT) state. The 1534Cyskdr allele varied from 3% (Marilena/PR and Porto Velho/RO) to 10% (Foz do Iguaçu/PR). To our knowledge, this paper reports the first occurrence and provides distribution data of a possible kdr mutation in Ae. albopictus in South America.ConclusionThe emergence of a likely kdr mutation in Ae. albopitus natural populations is a signal of alert for vector control measures since PY are the most popular insecticides adopted by residents. Additionally, once the kdr allele is present, its frequency tends to increase faster under exposition to those compounds. Although the Asian tiger mosquito is not incriminated as an important vector of dengue, chikungunya and Zika viruses in South America, its importance in this regard has been extensively discussed since Ae. albopictus is rapidly spreading and can also migrate between sylvatic and urban environments. Therefore, insecticide resistance monitoring initiatives should also be extended to Ae. albopictus in Brazil in order to maintain chemical compounds as an efficient vector control tool when needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2089-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: First report of the Phe1534Cyskdr mutation in natural populations of Aedes albopictusfrom Brazil

2017

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“…Second, CNVs can play a key role in the evolution of insecticide resistance due to their ability to affect gene expression and allow co-expression of wild-type and mutant alleles [10,11]. Despite nearly two decades of genetic research into insecticide resistance, known resistance-associated SNPs are still unable to explain much of the variance in insecticide resistance [12]. CNVs potentially represent a crucial source of missing variation that can fill this gap.…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes

Lucas

Miles

Harding³

et al. 2018

Preprint

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BackgroundPolymorphisms in the copy number of a genetic region can influence gene expression, coding sequence and zygosity, making them powerful actors in the evolutionary process. Copy number variants (CNVs) are however understudied, being more difficult to detect than single nucleotide polymorphisms. We take advantage of the intense selective pressures on the major malaria vector Anopheles gambiae, caused by the widespread use of insecticides for malaria control, to investigate the role of CNVs in the evolution of insecticide resistance.ResultsUsing the whole-genome sequencing data from 1142 samples in the An. gambiae 1000 genomes project, we identified 1557 independent increases in copy number, encompassing a total of 267 genes, which were enriched for gene families linked to metabolic insecticide resistance. The five major candidate genes for metabolic resistance were all found in at least one CNV, and were often the target of multiple independent CNVs, reaching as many as 16 CNVs in Cyp9k1. These CNVs have furthermore been spreading due to positive selection, indicated by high local CNV frequencies and extended haplotype homozygosity.ConclusionsOur results demonstrate the importance of CNVs in the response to selection, with CNVs being closely associated with genes involved in the evolution of resistance to insecticides, highlighting the urgent need to identify their relative contributions to resistance and to track their spread as the application of insecticide in malaria endemic countries intensifies. Our detailed descriptions of CNVs found across the species range provides the tools to do so.

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“…It is critically important that we understand the mechanisms responsible for this resistance to develop tools and strategies to mitigate against its potentially devastating effect. Two resistance mechanisms, alterations in the target site that reduce insecticide binding and increased rates of insecticide metabolism, have been the focus of the majority of previous studies on pyrethroid resistance in mosquitoes (Donnelly et al, 2009(Donnelly et al, , 2016. A subset of detoxification genes with elevated expression in multiple resistant populations of An.…”

Section: Introductionmentioning

confidence: 99%

TheAnopheles gambiaeATP‐binding cassette transporter family: phylogenetic analysis and tissue localization provide clues on function and role in insecticide resistance

Pignatelli

Ingham

Balabanidou

et al. 2017

Insect Molecular Biology

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The role of ATP-binding cassette (ABC) transporters in conferring insecticide resistance has received much attention recently. Here we identify ABC transporters differentially expressed in insecticideresistant populations of the malaria vector, Anopheles gambiae. Although we found little evidence that the orthologues of the multidrug resistance proteins described in other species are associated with resistance in An. gambiae we did identify a subset of ABC proteins consistently differentially expressed in pyrethroid-resistant populations from across Africa. We present information on the phylogenetic relationship, primary sites of expression and potential role of ABC transporters in mediating the mosquito's response to insecticides. Furthermore we demonstrate that a paralogous group of eight ABCG transporters, clustered on chromosome 3R, are highly enriched in the legs of An. gambiae mosquitoes, consistent with a proposed role for this ABC subfamily in transport of lipids to the outer surface of the cuticle. Finally, antibodies raised against one of the most highly expressed ABC transporters in adult females, ABCG7 (AGAP009850), localized this transporter to the pericardial cells. These data will help prioritize members of this gene family for further localization and functional validation studies to identify the in vivo function of these transporters in the mosquito and determine whether elevated expression of members of this family contribute to insecticide resistance.

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Identification, Validation, and Application of Molecular Diagnostics for Insecticide Resistance in Malaria Vectors

Cited by 102 publications

References 71 publications

RETRACTED ARTICLE: First report of the Phe1534Cyskdr mutation in natural populations of Aedes albopictusfrom Brazil

RETRACTED ARTICLE: First report of the Phe1534Cyskdr mutation in natural populations of Aedes albopictusfrom Brazil

Whole genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes

TheAnopheles gambiaeATP‐binding cassette transporter family: phylogenetic analysis and tissue localization provide clues on function and role in insecticide resistance

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