Researchers identify protein responsible for malaria transmission

Tuesday, February 25, 2014

Plasmodium falciparum gametocytes.

Two groups of researchers have independently identified the the protein responsible for malaria transmission to mosquitoes in studies published in journal Nature on Sunday.

The scientists found a direct relationship between the protein AP2-G's with malaria gametocytes (male and female sexual forms) production, which is necessary for the transmission. Only the sexual forms infect mosquitoes and sexual reproduction occurs within the mosquito digestive tract.

Malaria is caused by Plasmodium parasites. The initially separate teams looked at different plasmodium species. One, an international group led by Manuel Llinás of Penn State University in the US, examined Plasmodium falciparum, which is responsible for the worst form of human malarial infections; the other, led by UK scientists Oliver Billker from the Wellcome Trust Sanger Institute in England and Andy Waters from University of Glasgow in Scotland, looked at Plasmodium berghei, which infects rodents.

The P. falciparum group was kickstarted by research in Spain which found different organisms from the same strain with identical DNA had varying levels of AP2-G, with a strong correlation to their levels of sexual activity. The more AP2-G, the higher the rate of gametocyte formation. Researchers in England, later also drawn into the international team, analyzed the genomes of two mutated strains of P. falciparum which were both unable to form gametocytes. They found that the gene responsible for producing the AP2-G protein was the only common non-functioning gene.

The international team found found the AP2-G protein catalyzes the transmission by activating a relevant gene set in the parasite.

Women tend to their malaria-infected babies in Angola.
Image: USAID Africa.

Both teams confirmed the finding by gene therapy — both by adding the gene into a mutated strain and observing its ability to form gametocytes, and the other way round.

The parasites exist in a mosquito, then in a human, and require subsequent transmission for the parasite to spread. The transmission can only happen through gametocytes. The parasite triggers formation of the sexual gametocytes into the human's circulatory system every two days in small quantities — not wasting energy on the process at the dry time of year when few mosquitoes are available — but little was known about the mechanism.

Dr. Oliver Billker commented on the potential of getting the transmission of malaria under control, unlike the existing focus on addressing the phrase causing the clinical symptoms, "Current drugs treat patients by killing the sexless form of the parasite in their blood — this is the detrimental stage of the malaria lifecycle that causes illness. However, it is now widely accepted that to eliminate malaria from an entire region, it will be equally important to kill the sexual forms that transmit the disease."

The researchers hope to continue research toward drugs to prevent the transmission of the disease. The science was funded by groups including UK research councils, the Spanish government, the U.S. National Institutes of Health, and the European Commission.


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