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At the Liverpool School of Tropical Medicine, Professor Janet Hemingway is searching for the mosquito genes that confer resistance insecticides.
"We're using fine-scale molecular biology to take resistance genes apart, see what their function is, find the mutations that produce resistance, and find the genes that upregulate some of the enzymes that produce resistance," she says.
Feature: The mosquito resistance movement
Some mutations in mosquito proteins produce resistance directly. Most of the targets of insecticides are within the insect's nervous system – proteins such as the neurotransmitter acetylcholinesterase – and even small genetic changes can alter the target's shape, so the protein is no longer susceptible to the insecticide poisoning it.
Other resistant mosquitoes stop the insecticide before it reaches their critical systems. Proteins that can break down or soak up the insecticide – esterases, monooxogenases and glutathione S-transferases – are produced in regions such as the gut, salivary glands or subcuticular layer.
As the insecticide has to enter the insect through swallowing or through the cuticle, the proteins are ideally placed to screen out the insecticide.
The screening proteins produce resistance because they are produced in massive quantities. For example, some insects have 80 times the normal number of esterase genes in all of their cells. The insecticide is swamped by huge amounts of esterase proteins produced: up to 2 per cent of the total soluble protein of the insect.
While the mechanisms for esterase-driven resistance have been uncovered, those that lead to the overproduction of the monooxogenases and the glutathione S-transferases have remained more elusive.
"We know that there are regulatory mechanisms that control lots of genes," says Professor Hemingway, "and we've been able to narrow down where these regulatory genes are in the mosquito genome – but we're not sure what the genes are. Of course, the exciting development is the sequencing of the Anopheles genome. With the sequence available, we'll able to home in and identify the genes."
Looking ahead, Professor Hemingway thinks that in just a few years' time all the primary resistance genes and their regulators will have been found and their roles in resistance understood.
"Once we know about these gene systems, we can start to target them. We could extend the life of pyrethroids, for example, by adding something to the formulation that will affect the regulatory genes of the major resistance genes and switch them off."
Yet even modern genetics faces a formidable foe – the power of evolution. "It'll always be a game that you're playing with the insects," she points out. "We're putting them under huge selection pressure, and they may well find some route around the insecticides."
Professor Janet Hemingway is Director of the Liverpool School of Tropical Medicine.
Image credit: LJ Bruce-Chwatt
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