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Map of Essential Genes in Malaria-Causing Parasite Developed by Researchers
Researchers at Harvard T.H. Chan School of Public Health, in collaboration with other institutions, have unveiled a detailed map identifying all the essential genes linked to blood infections in the malaria-causing parasite Plasmodium knowlesi. This groundbreaking map represents the most comprehensive classification of key genetic components in the Plasmodium genus, offering potential pathways to discover new drug targets and tackling drug resistance—an increasing concern in malaria treatment.
Co-corresponding author Manoj Duraisingh, who serves as the John LaPorte Given Professor of Immunology and Infectious Diseases, expressed optimism about the research’s implications. “We hope that our findings are a major step forward for the field of malaria research and control. The emergence of drug resistance against the limited number of available antimalarial drugs poses a significant challenge, and this map will serve as a vital resource for researchers striving to address one of the leading infectious disease threats globally,” he stated.
The study is scheduled for publication on February 6, 2025, in the journal Science.
Malaria, caused by various Plasmodium species, affects approximately 249 million people each year, leading to about 608,000 fatalities annually. P. knowlesi is a zoonotic parasite that poses serious health risks and is increasingly recognized as a public health issue in Southeast Asia.
Utilizing a robust genetic methodology known as transposon mutagenesis, the researchers were able to disrupt the genes in P. knowlesi that are not essential for its growth in human red blood cells. This innovative technique revealed a comprehensive map of the genes that are crucial for the parasite’s proliferation. Through this process, the team also identified specific genes associated with resistance to existing antimalarials.
“Understanding the essential genes in P. knowlesi enables us to grasp the molecular tactics utilized by the parasite for growth, adaptation to environmental shifts, and responses to treatments like antimalarials,” remarked Sheena Dass, co-first author and a postdoctoral fellow in the Department of Immunology and Infectious Diseases. “This molecular blueprint will significantly assist malaria researchers in conducting biological studies focused on malaria and guide strategies to mitigate the emergence of drug resistance.”
Additionally, the researchers pointed out that their findings may provide insights into another malaria-causing species, P. vivax, which shares evolutionary ties with P. knowlesi. Since P. vivax is not easily cultivated or genetically manipulated, it presents unique challenges for malaria eradication efforts.
Brendan Elsworth and Sida Ye contributed as co-first authors, while Kourosh Zarringhalam from the University of Massachusetts, Boston, served as a co-corresponding author. Other contributors from Harvard Chan include Jacob Tennessen, Basil Thommen, Aditya Paul, Usheer Kanjee, and Christof Gruring.
The research received support from multiple sources, including the National Institutes of Health, the Swiss National Science Foundation, and the Food and Drug Administration’s Intramural Research Program.
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