Scientists Discover Gene That Makes Mosquitoes Resistant To DDT And Other Insecticides

By Shweta Iyer on February 25, 2014 3:10 PM EST

insecticide
Researchers have discovered that a single genetic mutation in mosquitoes makes them resistant to popular insecticides. (Photo: Photo courtesy of Shutterstock)

Dr. Charles Wondji and his team of researchers from Liverpool School of Tropical Medicine (LSTM) have discovered that a single genetic mutation in mosquitos makes them resistant to popular insecticides. This discovery is an important milestone for scientists to improve strategies for malaria control, according to a press release Tuesday. Dichlorodiphenyltrichloroethane, or "DDT," and pyrethroids (an insecticide class used in mosquito nets) are used extensively in mosquito control. But DDT and pyrethoid-resistant mosquitos have started increasing in numbers thereby reducing the effectiveness of these chemicals. 

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Dr. Wondji and his team conducted many tests and narrowed down the ability of mosquitos to develop resistance to DDT, to a single gene. Mutation in the GSTe2 gene of the mosquito's DNA, makes the insect capable of breaking down the DDT and rendering it nontoxic. Researchers have also shown that this gene makes mosquitos resistant to pyrethroids. This is of huge concern to health officials since DDT and pyrethroids are used for large area mosquito control. Every year countless mosquitos bite and transmit malarial parasites into millions of people. Controlling mosquito population by use of insecticides is an important strategy for preventing the spread of the disease. The spread of resistance genes could hamper efforts taken to prevent the disease. The researchers say 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. So we wanted to elucidate the molecular basis of that resistance in the population and design a field applicable diagnostic assay for its monitoring," said Dr. Wondji.

The researchers did a genome-wide comparison between mosquitos from Pahou in Benin, which were DDT resistant and laboratory mosquitos that were DDT nonresistant. They identified the GSTe2 gene as being upregulated, that is producing a lot of protein in the Benin mosquitoes.They found that a single mutation (L119F) changed a nonresistant 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 tested it on mosquitos from different parts of the world. It was confirmed that this mutation was found in mosquitoes present in areas where DDT resistance had been established whereas absent in regions where mosquitos were still susceptible to DDT. 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.

The researchers further confirmed the role of GSTe2 gene in inducing resistance by introducing it into fruit flies (Drosophila melanogaster), which became resistant to DDT and permethrin, an insecticide of the pyrethroid class.

"For the first time, we have been able to identify a molecular marker for metabolic resistance (the type of resistance most likely to lead to control failure) in a mosquito population and to design a DNA-based diagnostic assay. Such tools will allow control programs to detect and track resistance at an early stage in the field, which is an essential requirement to successfully tackle the growing problem of insecticide resistance in vector control. This significant progress opens the door for us to do this with other forms of resistance as well and in other vector species", said Wondji.

Source: Riveron, JM. Wondji CS. A single mutation in the GSTe2 gene allows tracking of metabolically-based insecticide resistance in a major malaria vector.  Genome Biology. 2014.   

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