US-team led by UT Southwestern Medical Centre researchers has discovered why some mosquitoes are resistant to malaria, a finding that may one day help fight the dreaded disease.
The researchers focused on TEP1, a protein in the mosquito’s immune system. When a mosquito is infected with a parasite that causes malaria, a biochemical reaction is triggered that physically transforms TEP1 into an active state, capable of targeting the parasite for termination.
In a study appearing online this week in the Proceedings of the National Academy of Sciences, the researchers found that the genetic differences
between mosquitoes that are resistant and those that are susceptible to the parasite mostly manifest in a region of the TEP1 protein dubbed “the warhead,” the portion that grabs the malarial parasite.
“TEP1 is a scout that finds the malarial parasites, then plants a homing signal on it and calls in the air strike,” said Dr Richard Baxter, a researcher at UT Southwestern and lead author of the study.
Understanding how some mosquitoes can fend off malaria might someday lead to reducing or even eliminating the mosquito’s capacity to transmit the devastating disease, Dr Baxter said.
Dr Johann Deisenhofer, a professor of biochemistry and senior author of the study, said, “This finding opened my eyes to the fact that mosquitoes are almost as unhappy about malaria as we are. They try to get rid of it.”
Malaria a leading cause of disease and death affects about 500 million people worldwide. It is caused by parasites of the genus Plasmodium, which are spread to humans through mosquito bites.
The research group’s French collaborators, Institut de Biologie Molculaire et Cellulaire in Strasbourg, had reviously determined that the gene for TEP1 occurs in two forms: TEP1r occurs in mosquitoes that are resistant to malaria, while TEP1s is found in those that are vulnerable to it.
The TEP1r and TEP1s proteins are 93 per cent genetically identical, and the new study shows that the differences cluster around the warhead area, Dr Baxter said. This finding reinforces the theory that the warhead is a key element of the overall immune response to malaria in mosquitoes.
In future studies, the researchers will genetically manipulate the warhead to study its properties, Dr Baxter said. In addition, further research is needed to determine what other elements of the mosquito’s immune system are activated once TEP1 binds to an invader.
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