Scientists crack secret of mosquito resistance to insecticides

Scientists have found that a single genetic mutation causes mosquitoes to develop resistance to DDT and to insecticides used in anti-malaria nets.
Mosquitoes (Anopheles funestus) are vectors of malaria, and most strategies for combating the spread of the disease focus on control of mosquito populations using insecticides.
The findings could help improve malaria control strategies, said researchers from UK's Liverpool School of Tropical Medicine.
The researchers, led by Dr Charles Wondji, used a wide range of methods to narrow down how the resistance works, finding a single mutation in the GSTe2 gene, which makes insects break down DDT so it's no longer toxic.

They have also shown that this gene makes insects resistant to pyrethroids raising the concern that GSTe2 gene could protect mosquitoes against the major insecticides used in public health.
Researchers said that knowing how resistance works will help to develop tests, and stop these genes from spreading amongst mosquito populations.

"We found a population of mosquitoes fully resistant to DDT (no mortality when they were treated with DDT) but also to pyrethroids," Wondji said.
"So we wanted to elucidate the molecular basis of that resistance in the population and design a field applicable diagnostic assay for its monitoring," he added.

They took mosquitoes from Pahou in Benin, which were resistant to DDT and pyrethroids, and mosquitoes from a laboratory fully susceptible strain and did a genome wide comparison study.
They identified the GSTe2 gene as being upregulated - producing a lot of protein - in Benin mosquitoes.
They found that a single mutation (L119F) changed a non-resistant version of the GSTe2 gene to a DDT resistant version.
They designed a DNA-based diagnostic test for this type of resistance (metabolic resistance) and confirmed that this mutation was found in mosquitoes from other areas of the world with DDT resistance but was completely absent in regions without.

X-ray crystallography of the protein coded by the gene illustrated exactly how the mutation conferred resistance, by opening up the 'active site' where DDT molecules bind to the protein, so more can be broken down.
This means that the mosquito can survive by breaking down the poison into non-toxic substances.
They also introduced the gene into fruit flies (Drosophila melanogaster) and found they became resistant to DDT and pyrethroids compared to controls, confirming that just this single mutation is enough to make mosquitoes resistant to both DDT and permethrin.
The study was published in the journal Genome Biology.