MONDAY, MARCH 19, 2018

Scientists discover important protein in malaria reproduction

Researchers discovered that one regulatory protein serves as the master genetic switch that causes the development of male and female sexual forms of the malaria parasite, according to studies recently published in Nature.

Two teams independently discovered that AP2-G is needed by the malaria parasite to activate a set of genes initiating the development of gametocytes. Gametocytes are the only forms of the parasite that are infectious to mosquitoes. The findings may provide clues to identifying the mechanisms that control whether or not a malaria parasite can transmit the disease.

Malaria-causing Plasmodium parasites produce only a small number of sexual parasites during each two-day lifecycle. The strategy ensures survival during dry seasons when mosquitoes are rare and represents a potential vulnerability. Researchers have struggled to find out how the parasites decide to produce sexual stages.

"This sexual-stage bottleneck is an enticing target for interventions to prevent this comparatively small, yet critical number of sexual parasites from forming," Manuel Llinas, an associate professor at Penn State University, said. "If the sexual forms of the parasite never develop in an infected person's blood, then none will get into the mosquito's gut, and the mosquito will not be able to infect anyone else with malaria."

Llinas' team and a separate team of researchers led by the Wellcome Trust Sanger Institute and the University of Glasgow independently determined the role of the same AP2-G transcriptional regulator. Llinas said that in his team's study, the level of sexual-stage parasites produced by Plasmodium clones matched the proportion of individual cells specifically producing the AP2-G protein.

"Our results perfectly correlate the expression of the AP2-G gene with the number of sexual-stage malaria parasites formed." Llinas said.

The researchers said discoveries related to the AP2-G protein open the way to develop assays to screen for effective drugs able to disable malaria's commitment to sexual development and disease transmission.

"With the help of the next-generation technologies that we and other malaria researchers now are using, we are optimistic about more discoveries for malaria control that could occur soon -- even during the next 5 years," Llinas said.