World Malaria Day: The Weak Links in the Malaria Cycle
In advance of World Malaria Day on Friday, Shyama Ghosh takes a look at some of the developments that have recently taken place in the Malaria field.
For the first time, researchers have identified a single protein that is essential to the spread of malaria. The AP-2G protein acts as a master switch that triggers the development of sexual forms of the malaria parasite, a stage essential for the spread of the disease.
Within human red blood cells (RBCs), the Plasmodium parasite continues its growth by asexual multiplication and invasion of fresh RBCs. At regulated time intervals (48 hours for P. falciparum, P. vivax, P. ovale, 72 hours for P. malariae), infected RBCs burst releasing numerous asexual stages that infect fresh RBCs and coincide with fever, chills and shivering in the human host, which are the hallmark of the infection. From time to time some of these parasites differentiate to micro and macro gametocytes – the sexual forms that fuse in the midgut of the female Anopheles mosquito following a blood meal. The protein, AP2-G, is necessary for switching on genes that control this developmental change from asexual forms to sexual parasite entities – the only stage that is infectious to mosquitos. The discovery of this protein opens a range of possibilities for control or eradication of malaria. This research is now published in Nature.
“Exciting opportunities now lie ahead for finding an effective way to break the chain of malaria transmission by preventing the malaria parasite from completing its full life cycle,” says Dr. Manuel Llinás, from Penn State University, describing the discovery of AP2-G. “This sexual-stage bottleneck is an enticing target for interventions to prevent this comparatively small yet critical number of sexual parasites from forming.”
Researchers involved believe that the discovery of AP-2G opens the way to the development of screens for effective drugs that could disable commitment to sexual development and prevent transmission. “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,” states Dr. Oliver Billker from the Wellcome Trust Sanger Institute.
“Our studies discovered that if we switch off AP2-G in a parasite cell, then that cell cannot grow into a sexual-stage parasite,” says Dr. Andy Waters, University of Glasgow. “This means that the parasite cannot move from the infected person back into the mosquito to continue the cycle, making transmission of that parasite from one human to another impossible.”
“Having discovered the master switch, we can now begin to unravel how exactly sexual parasite stages form and get ready to transmit malaria,” says Dr. Katarzyna Modrzynska, from the Wellcome Trust Sanger Institute. “This will reveal new ways in which drugs and vaccines can be developed to stop transmission.”
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