Predictive chemoproteomics and functional validation reveal Coeae6g-mediated insecticide cross-resistance in the malaria vector Anopheles gambiae

Sofia Balaska, Linda Grigoraki (), Gareth Lycett, David Weetman, Folasade Oladepo, Fraser Colman, John Vontas, Mark J. I. Paine and Hanafy M. Ismail ()
Additional contact information
Sofia Balaska: Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology
Linda Grigoraki: Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology
Gareth Lycett: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine
David Weetman: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine
Folasade Oladepo: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine
Fraser Colman: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine
John Vontas: Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology
Mark J. I. Paine: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine
Hanafy M. Ismail: Pembroke Place, Department of Vector Biology, Liverpool School of Tropical Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Sustaining malaria control in Africa is imperilled by the rapid evolution of insecticide resistance in the major vector Anopheles gambiae. Although current genomic and transcriptomic approaches map known resistance alleles, they often lack predictive power to anticipate liabilities to new insecticides. We present a predictive functional chemoproteomic framework integrating competitive activity-based protein profiling with functional validation to identify enzyme-mediated resistance mechanisms before they arise in field populations. Applied to a susceptible Anopheles gambiae strain, fluorophosphonate probe profiling with pirimiphos-methyl-oxon, the bioactive metabolite of the organophosphate pirimiphos-methyl, revealed 18 active serine hydrolases. The carboxylesterase Coeae6g was selected for further functional analysis because it had previously been shown to be associated with pyrethroid and carbamate resistance. Functional assays confirmed Coeae6g confers resistance to pirimiphos-methyl and mediates cross-resistance to malathion, bendiocarb, and permethrin. These findings bridge genotype–phenotype gaps, align with emerging field genomic signatures, and establish a scalable framework to complement genomic surveillance and guide insecticide management in malaria vector control.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65827-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65827-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65827-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().