Insecticides play a key role in the control of mosquito borne diseases. The limited number of insecticide classes available for use in public health (currently four) and the growing levels of resistance to all of these chemicals in a range of mosquito species is a growing impediment to disease control. This problem is particularly acute in malaria control where the impressive gains achieved using insecticide treated bednets or indoor residual spraying with insecticides are in danger of being eroded by growing resistance in the Anopheles mosquito vectors. A variety of genetic screening tools have been used to identify the small subset of mosquito P450s that are over expressed in insecticide resistant populations. Recombinant proteins for each of these have been generated and screened against a panel of WHO approved insecticides. Antibodies have been used to identify the major tissues in which each of the major candidates are expressed and to confirm that these enzymes are expressed at elevated levels in insecticide resistant populations. Enzymes in the CYP6P, CYP6M and CYP6Z families have all been implicated in conferring insecticide resistance by this approach. Recently, a specific role for the CYP4G enzymes in cuticular resistance has been proposed and is being further investigated. The next challenge is to develop molecular markers to track these resistance mechanisms in field populations to aid in resistance monitoring. Ultimately, it is hoped that knowledge on the P450s responsible for insecticide resistance and their mode of action will accelerate the development of new chemistries that are urgently needed for malaria control.

P450s responsible for insecticide resistance in malaria vectors: Finding them, tracking them, stopping them?

246th National Meeting (2013)

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