Exploring the metabolic and cuticular mechanisms of increased pyrethroid resistance in Anopheles gambiae S.l populations from Ghana.

Increasing insecticide resistance in malaria vectors threatens the efficacy of current control tools, however knowledge of metabolic and cuticular mechanisms is widely lacking in Ghana. We examined the metabolic and cuticular resistance mechanisms in Anopheles gambiae mosquitoes from coastal and sahel zones of Ghana. WHO susceptibility tests and synergist assays were performed on F0 field collected An. gambiae s.l. Gene expression profiles of eight key metabolic and cuticular genes were determined using qRT-PCR. Moderate to high pyrethroid resistance (< 70%) were observed across all the sites. Piperonyl butoxide significantly increased susceptibility to pyrethroids across all sites and insecticides, implicating P450s. Gene expression analysis revealed overexpression of metabolic and cuticular resistance genes in field An. gambiae populations compared to the susceptible Kisumu strain. CYP6M2 and CYP6P3 were the most overexpressed metabolic genes in pyrethroid-resistant mosquitoes, compared to the pyrethroid susceptible mosquitoes in the coastal (FC: 122.28 and 231.86, p < 0.05) and sahel (FC: 344.955 and 716.37, p < 0.001) zones respectively. CYP4G16 (previously associated with cuticular resistance) was significantly overexpressed in only resistant mosquitoes (FC: 3.32-30.12, p < 0.05). Overexpression of metabolic and cuticular resistance genes in local malaria vectors highlights the need to intensify insecticide resistance management strategies to control malaria in Ghana.