Role of Cytochrome P450s in Insecticide Resistance in Anopheles gambiae (Diptera: Culicidae): The African Perspective

Cytochrome P450s are known to be critical for the detoxification and/or activation of xenobiotics such as insecticides in all living organisms including Anopheles gambiae. Many studies have demonstrated the role of P450s in insecticide resistance in An. gambiae. However, little is known about the impact of distribution in the African sub-continent. In this paper therefore, we analyse the P450 clans, the CYP6 family, localisation and function of An. gambiae CYPs, their insecticide substrates, regional distribution in the African continent and their role in insecticide resistance. This investigation from published data revealed that in the Central region; CYP6Z3, CYP6Z1, CYP12F2, CYP6P4, CYP6GA1, CYP6Z3 (Yaoundé, Cameroun) have bendiocarb, DDT and pyrethroids as substrates; in the Eastern region: CYP314A1 and CYP12F1 (Tanzania and Zanzibar) have DDT as a substrate, CYP32A3, CYP6Z1 and CYP6Z2 (Western Kenya) have DDT and carbaryl and permethrin; whilst in the Western region: CYP6AG1, CYP6Z2, CYP6Z3, CY6P3, CYP6P4, CYP6M2 (Ghana), CYP6M2, CYP6P3 (Benin), CYP325A3, CYP6P3 and CYP6M2 (Nigeria) all have DDT, carbaryl, permethrin, trans-and cis-permethrin, deltamethrin, bendiocarb as substrates. Additionally, CYP6M2, CYP6P3, CYP6Z3 (Côte d’Ivoire), CYP6P3, CYP6Z2 and CYP9J5 (Burkina Faso) have bendiocarb, DDT plus pyrethroids and only pyrethroids as substrates respectively. Interestingly, CYP6P3 is observed to metabolize all the available insecticides (DDT, pyrethroid, trans- and cis-permethrin, deltamethrin and bendiocarb), indicating possible insecticide cross resistance across all the three regions of Africa. A more detailed understanding of the substrate specificities of various P450s and the geographical distribution of insecticide resistance in Africa is quintessential for an effective resistance management.