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Researchers at Harvard T.H. Chan School of Public Health and their collaborators created a comprehensive map of genes needed for blood infections from Plasmodium knowlesi (P. knowlesi). This organism is the parasite responsible for malaria in humans. With the most complete classification of essential genes in any Plasmodium species, this map serves as a valuable tool for identifying druggable targets, understanding resistance mechanisms, and aiding in the development of new malaria treatments.
“We hope that our findings are a major step for the field of malaria research and control,” stated co-corresponding author Manoj Duraisingh, John LaPorte Given Professor of Immunology and Infectious Diseases. “Emerging drug resistance to the small number of antimalarial drugs is a growing problem. This map will be an invaluable resource to help researchers combat one of the leading causes of infectious disease death around the world.”
Malaria remains a major global health burden, with approximately 249 million cases and 608,000 deaths annually. P. knowlesi, a zoonotic malaria parasite, is an emerging public health concern in Southeast Asia. Understanding its genetic requirements for survival and drug resistance mechanisms promopted the research team to create this comprehensive genetic map.
The researchers used transposon mutagenesis to systematically disrupt nonessential genes and identify those critical for Plasmodium knowlesi survival in human red blood cells. This large-scale approach enabled them to identify genes necessary for blood-stage infection and those that contribute to drug resistance.
“Knowing all of the essential genes in P. knowlesi allows us to understand the molecular strategies that the parasite takes to grow, to respond to environmental changes, and to respond to therapeutics such as antimalarials,” said co-first author Sheena Dass, Postdoctoral Fellow in the Department of Immunology and Infectious Diseases. “This molecular blueprint will help malaria researchers in the design and execution of biological studies of malaria as well as inform strategies to monitor and limit the emergence of drug resistance.”
The researchers noted that the findings also provide insights into one other malaria-causing Plasmodium species, P. vivax, due to their evolutionary relatedness. P. vivax, which is poorly studied because it is not culturable or genetically tractable, is a major challenge to elimination efforts.
Publication Details
Brendan Elsworth et al., The essential genome of Plasmodium knowlesi reveals determinants of antimalarial susceptibility. Science 387, eadq6241 (2025). DOI:10.1126/science.adq6241
“We hope that our findings are a major step for the field of malaria research and control,” stated co-corresponding author Manoj Duraisingh, John LaPorte Given Professor of Immunology and Infectious Diseases. “Emerging drug resistance to the small number of antimalarial drugs is a growing problem. This map will be an invaluable resource to help researchers combat one of the leading causes of infectious disease death around the world.”
Malaria remains a major global health burden, with approximately 249 million cases and 608,000 deaths annually. P. knowlesi, a zoonotic malaria parasite, is an emerging public health concern in Southeast Asia. Understanding its genetic requirements for survival and drug resistance mechanisms promopted the research team to create this comprehensive genetic map.
The researchers used transposon mutagenesis to systematically disrupt nonessential genes and identify those critical for Plasmodium knowlesi survival in human red blood cells. This large-scale approach enabled them to identify genes necessary for blood-stage infection and those that contribute to drug resistance.
“Knowing all of the essential genes in P. knowlesi allows us to understand the molecular strategies that the parasite takes to grow, to respond to environmental changes, and to respond to therapeutics such as antimalarials,” said co-first author Sheena Dass, Postdoctoral Fellow in the Department of Immunology and Infectious Diseases. “This molecular blueprint will help malaria researchers in the design and execution of biological studies of malaria as well as inform strategies to monitor and limit the emergence of drug resistance.”
The researchers noted that the findings also provide insights into one other malaria-causing Plasmodium species, P. vivax, due to their evolutionary relatedness. P. vivax, which is poorly studied because it is not culturable or genetically tractable, is a major challenge to elimination efforts.
Publication Details
Brendan Elsworth et al., The essential genome of Plasmodium knowlesi reveals determinants of antimalarial susceptibility. Science 387, eadq6241 (2025). DOI:10.1126/science.adq6241