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Background  Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations. Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms. Several metabolic enzymes have been implicated in insecticide resistance but the processes controlling their expression have remained largely elusive.    Results  Here, we show that the transcription factor  Maf-S  regulates expression of multiple detoxification genes, including the key insecticide metabolisers  CYP6M2  and  GSTD1  in the African malaria vector  Anopheles gambiae . Attenuation of this transcription factor through RNAi induced knockdown reduced transcript levels of these effectors and significantly increased mortality after exposure to the pyrethroid insecticides and DDT (permethrin: 9.2% to 19.2% ( p  = 0.015), deltamethrin: 3.9% to 21.6% ( p  = 0.036) and DDT: 1% to 11.7% (p = <0.01), whilst dramatically decreasing mortality induced by the organophosphate malathion (79.6% to 8.0% (p = <0.01)). Additional genes regulated by  Maf-S  were also identified providing new insight into the role of this transcription factor in insects.    Conclusion    Maf-S  is a key regulator of detoxification genes in  Anopheles  mosquitoes. Disrupting this transcription factor has opposing effects on the mosquito’s response to different insecticide classes providing a mechanistic explanation to the negative cross resistance that has been reported between pyrethroids and organophosphates.    Electronic supplementary material  The online version of this article (10.1186/s12864-017-4086-7) contains supplementary material, which is available to authorized users.

The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae