Field-evolved resistance to neonicotinoids in the mosquito, Anopheles gambiae, is associated with downregulation and mutations of nicotinic acetylcholine receptor subunits combined with cytochrome P450-mediated detoxification

Neonicotinoid insecticides act selectively on their nicotinic receptor targets leading to variable sensitivity among arthropods. This study aimed to investigate the molecular mechanisms underlying contrasting susceptibility to neonicotinoids observed in wild populations of two mosquito sibling species. Bioassays and a synergism test revealed that the sister taxa, Anopheles gambiae and An. coluzzii, from Yaounde, Cameroon, rely on cytochrome P450s to detoxify neonicotinoids and develop resistance. However, contrary to An. coluzzii, An. gambiae populations are evolving stronger resistance to several active ingredients facilitated by mutations and reduced expression of nicotinic acetylcholine receptors. Six mutations were detected in coding sequences of the β1 and α6 subunits, including two substitutions in one of the loops that modulate ligand binding and sensitivity. Allele frequencies were strongly correlated with a susceptibility gradient between An. coluzzii and An. gambiae suggesting that the mutations may play a key role in sensitivity. Messenger RNA expression levels of the β1, α3, and α7 subunits decreased dramatically, on average by 23.27, 17.50, 15.80-fold, respectively, in wild An. gambiae populations compared to a susceptible insectary colony. By contrast, only the β2 and α9-1 subunits were moderately downregulated (5.28 and 2.67-fold change, respectively) in field-collected An. coluzzii adults relative to susceptible colonized mosquitoes. Our findings provide critical information for the application and resistance management of neonicotinoids in malaria prevention.

• Publication year

  2024

• Venue

  bioRxiv

• Publication date

  2024-08-17

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1101/2024.08.17.608399PMID 39185195PMCID 11343199
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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