New studies profile malaria parasite evolution and gene essentiality
Malaria, which still kills over 600,000 people every year, is caused by a number of parasites in the genus Plasmodium. There are two main Plasmodium species that cause malaria: Plasmodium falciparum, which is responsible for most malaria cases in sub-Saharan Africa; and Plasmodium vivax, which causes most malaria cases outside of Africa. Antimalarial drugs target the genes that these parasites need to grow, so understanding their genetic makeup is paramount. However, P. vivax cannot be grown in a lab setting, which poses a challenge to ensuring the effectiveness of antimalarials. In a new pair of studies, two teams of researchers used a close relative of P. vivax, P. knowlesi, to identify the genes necessary for its survival.
In both studies, the scientists performed mutagenesis screens, where cells are mutated randomly across their genomes to break their genes. After growing the cells, the scientists sequence all the break sites. Any gene required for the cell’s growth wouldn’t have any break sites, since natural selection would purge any cell containing such a break site. From these screens, the scientists calculated how essential each P. knowlesi gene is. Researchers for one of the studies specifically looked at genes targeted by antimalarials and found that, while most were essential in both species, a few metabolism-related genes were essential in only one of the species, meaning that antimalarials targeting those genes would likely perform less consistently.
These studies provide a wealth of information for the development of new antimalarial drugs and vaccines. Drug resistance is a growing issue in antimalarial interventions, so having drugs that target many parts of Plasmodium biology and that work across all Plasmodium species is a high priority.
The first study was led by Sheena Dass, a postdoctoral fellow, Sida Ye, a computational scientist, and Brendan Elsworth, a researcher, all at the Harvard Chan School of Public Health. The second study was led by Jenna Oberstaller and Shulin Xu, a postdoctoral researcher and research associate, respectively at the College of Public Health at University of South Florida, and Deboki Naskar, a researcher at the Cambridge Institute for Medical Research at the University of Cambridge.
Managing Correspondent: Alex Yenkin
Press Article: “Malaria Parasite Adaptations Identified in Mutagenesis Studies“, GenomeWeb
Original Articles: “Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites,” Science
Image Credit: Red Blood Cell Infected with Malaria Parasites, from NIAID