Genetic variation associated with increased insecticide resistance in the malaria mosquito, Anopheles coluzzii

Bradley Main, Amanda Everitt, Anthony J. Cornel, Fereydoun Hormozdiari, Gregory C Lanzaro

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Malaria mortality rates in sub-Saharan Africa have declined significantly in recent years as a result of increased insecticide-treated bed net (ITN) usage. A major challenge to further progress is the emergence and spread of insecticide resistance alleles in the Anopheles mosquito vectors, like An. coluzzii. A non-synonymous mutation in the para voltage-gated sodium channel gene reduces pyrethroid-binding affinity, resulting in knockdown resistance (kdr). Metabolic mechanisms of insecticide resistance involving detoxification genes like cytochrome P450 genes, carboxylesterases, and glutathione S-transferases are also important. As some gene activity is tissue-specific and/or environmentally induced, gene regulatory variation may be overlooked when comparing expression from whole mosquito bodies under standard rearing conditions. Results: We detected complex insecticide resistance in a 2014 An. coluzzii colony from southern Mali using bottle bioassays. Additional bioassays involving recombinant genotypes from a cross with a relatively susceptible 1995 An. coluzzii colony from Mali confirmed the importance of kdr and associated increased permethrin resistance to the CYP9K1 locus on the X chromosome. Significant differential expression of CYP9K1 was not observed among these colonies in Malpighian tubules. However, the P450 gene CYP6Z1 was overexpressed in resistant individuals following sublethal permethrin exposure and the carboxylesterase gene COEAE5G was constitutively overexpressed. Conclusions: The significant P450-related insecticide resistance observed in the 2014 An. coluzzii colony indicates that ITNs treated with the P450 inhibitor piperonyl butoxide (PBO) would be more effective in this region. The known insecticide resistance gene CYP6Z1 was differentially expressed exclusively in the context of sublethal permethrin exposure, highlighting the importance of tissue-specificity and environmental conditions in gene expression studies. The increased activity of the carboxylesterase COEAE5G in the resistant An. coluzzii colony suggests resistance to other insecticides like organophosphates. Additional gene expression studies involving other tissues (e.g. fat body) would provide a more comprehensive view of genes underlying metabolic insecticide resistance in An. coluzzii from Mali. Identifying genetic markers linked to these regulatory alleles is an important next step that would substantially improve insecticide resistance surveillance and population genetic studies in this important vector species.

Original languageEnglish (US)
Article number225
JournalParasites and Vectors
Volume11
Issue number1
DOIs
StatePublished - Apr 4 2018

Fingerprint

Insecticide Resistance
Anopheles
Culicidae
Malaria
Mali
Permethrin
Genes
Carboxylesterase
Biological Assay
Insecticide-Treated Bednets
Carboxylic Ester Hydrolases
Alleles
Piperonyl Butoxide
Malpighian Tubules
Voltage-Gated Sodium Channels
Gene Expression
Pyrethrins
Organ Specificity
Fat Body
Organophosphates

Keywords

  • Adaptive introgression
  • Anopheles
  • Carboxylesterase
  • Insecticide resistance
  • kdr
  • Malaria vector
  • P450

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Genetic variation associated with increased insecticide resistance in the malaria mosquito, Anopheles coluzzii. / Main, Bradley; Everitt, Amanda; Cornel, Anthony J.; Hormozdiari, Fereydoun; Lanzaro, Gregory C.

In: Parasites and Vectors, Vol. 11, No. 1, 225, 04.04.2018.

Research output: Contribution to journalArticle

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