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Genetic Studies of Vector Species

Genetic Studies of Vector Species

285 - Overexpression of cytochrome P450s and cuticular genes may be driving reduced PBO synergy in intensely resistant populations of the major malaria vector Anopheles coluzzii

Thursday, March 6, 2025
11:45 AM – 11:55 AM AST
Location: 209
Abstract: Insecticide resistance may severely threaten the efficacy of contemporary malaria vector control programmes. Piperonyl butoxide (PBO) is a synergist which restores pyrethroid susceptibility by inhibiting mosquito detoxification enzymes and is incorporated into some dual-active ingredient insecticide-treated nets (ITNs). Recent clinical trials have demonstrated that PBO-containing ITNs are more protective against malaria, compared to pyrethroid and they have been recommended by the World Health Organization in areas where there is evidence of monooxygenase-based resistance mechanisms in the main malaria vector species. However, some Anopheles (An.) populations present reduced PBO synergy and the genetic mechanisms driving this are currently unclear. The targeted PCR assays used in routine entomological surveillance can only detect known resistance mechanisms and are therefore rapidly outdated as mosquitoes evolve. Next-generation sequencing methods (NGS) enable detection of novel, emerging resistance mechanisms. We performed whole transcriptome sequencing (RNA-seq) and 16S rRNA sequencing on permethrin exposed An. coluzzii who did and did not display PBO synergy. We identified genes which were significantly upregulated in permethrin resistant and/or exposed An. coluzzii, notably detoxification enzymes CYP6AF1, CYP6AF2 and CYP6P3, and cuticular protein CPR24. Pre-exposure to PBO resulted in suppression of many CYP and cuticular genes, but overexpression was still high in comparison to susceptible mosquitoes. Cuticular genes CPR83, PCLCA3 and CPR61 were upregulated in response to PBO pre-exposure. We also characterised the microbial profiles of An. coluzzii, showing that regardless of phenotype, Asaia was the dominant genus. After Asaia, Tanticharoenia was the second highest frequency in PBO-permethrin resistant mosquitoes, whilst Staphylococcus was second most abundant in PBO-permethrin susceptible and permethrin-only resistant mosquitoes. Elizabethkingia was the third most abundant genus across all phenotypes. NGS methods provide key information about insecticide resistance mechanisms in malaria vectors, which is essential to ensure the long-term sustainability of vector control programmes.