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A Sensory Appendage Protein Protects Malaria Vectors From Pyrethroids

Nicholas Liao

Nature. 2020 Jan;577(7790):376-380. doi: 10.1038/s41586-019-1864-1. | PubMed

Victoria A Ingham1, Amalia Anthousi2, Vassilis Douris3,4, Nicholas J Harding5, Gareth Lycett2, Marion Morris2, John Vontas3,6, Hilary Ranson7

  1. Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK. victoria.ingham@lstmed.ac.uk.
  2. Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
  3. Foundation for Research and Technology - Hellas (FORTH), Institute of Molecular Biology and Biotechnology, Heraklion, Greece.
  4. Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece.
  5. The Big Data Institute, University of Oxford, Oxford, UK.
  6. Pesticide Science Laboratory, Department of Crop Science, Agricultural University of Athens, Athens, Greece.
  7. Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK. hilary.ranson@lstmed.ac.uk.

Abstract

Pyrethroid-impregnated bed nets have driven considerable reductions in malaria-associated morbidity and mortality in Africa since the beginning of the century1. The intense selection pressure exerted by bed nets has precipitated widespread and escalating resistance to pyrethroids in African Anopheles populations, threatening to reverse the gains that been made by malaria control2. Here we show that expression of a sensory appendage protein (SAP2), which is enriched in the legs, confers pyrethroid resistance to Anopheles gambiae. Expression of SAP2 is increased in insecticide-resistant populations and is further induced after the mosquito comes into contact with pyrethroids. SAP2 silencing fully restores mortality of the mosquitoes, whereas SAP2 overexpression results in increased resistance, probably owing to high-affinity binding of SAP2 to pyrethroid insecticides. Mining of genome sequence data reveals a selective sweep near the SAP2 locus in the mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso) with the observed increase in haplotype-associated single-nucleotide polymorphisms mirroring the increasing resistance of mosquitoes to pyrethroids reported in Burkina Faso. Our study identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to malaria control efforts.

Presented By Victoria Ingham