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Scientists identify mosquito genes linked to insecticide resistance

5 February 2009

Anopheles funestus
Researchers funded by the Wellcome Trust have identified specific mosquito genes associated with resistance to a common class of insecticide. This is a significant step towards more effective malaria control strategies.

Malaria is one of the most serious diseases worldwide, killing more than one million people per year. Most of these are children under five years of age. Efforts to eliminate this mosquito-borne illness rely heavily on preventive measures, but there are growing concerns about resistance to insecticides.

Eradication of mosquitoes that carry the malarial parasite has relied heavily on spraying insecticides inside homes and treatment of mosquito netting. There are very few insecticides that are both effective and low cost, while at the same time safe for humans.

Developing new insecticides will be both time-consuming and expensive, so understanding the genetic and biological basis of resistance to insecticides currently in use will be critical to discovering more effective preventive measures.

Now, in research published online today in Genome Research, an international team of scientists led by Dr Charles Wondji, a Wellcome Trust Research Career Development Fellowship at the Liverpool School of Tropical Medicine, has identified the genetic basis of resistance to common pyrethroid insecticides in the mosquito Anopheles funestus, one of the major malarial vectors in Africa.

The group studied strains of A. funestus that are susceptible to pyrethroids and others that are resistant, and narrowed down the potential genetic culprits to members of a family of genes coding for enzymes known as cytochrome P450s. The P450s are common to all classes of organisms, and are considered a first line of defence against toxins. The researchers found two cytochrome P450 genes in A. funestus that are associated with pyrethroid resistance.

Dr Hilary Ranson of the Liverpool School of Tropical Medicine is a co-author of the study. She explained that what makes this finding remarkable is that this particular group of cytochrome P450s has also recently been implicated in pyrethroid resistance in Anopheles gambiae, the other major malaria-carrying mosquito in Africa.

"If the enzymes responsible for resistance are very similar in both species, there is a much greater incentive to invest efforts in identifying specific enzyme inhibitors in the knowledge that they will likely to be effective at overcoming resistance in both major malaria vectors," says Dr Ranson. Furthermore, she notes, it is critical that these mosquito P450 genes do not have close relatives in the human genome. This will mean that targets developed against these mosquitoes should have a low risk of toxicity in humans.

Image credit: James Gathany

Reference

Wondji CS et al. Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector. Genome Res [epub ahead of print]

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