Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes
Hall, Joanna M.
Almond, Neil M.
Mitchell, Graham Howard
Holder, Anthony A.
Blackman, Michael J.
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Biological and Environmental Sciences and Engineering (BESE) Division
Computer Science Program
Pathogen Genomics Laboratory
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AbstractResearch into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.
SponsorsThis work was supported by the United Kingdom Medical Research Council (U117532063 and U117532067), the European Community's FP7 Programme under Grant Agreement 242095 (EviMalar), and a Medical Research Council Career Development fellowship (to R. W. M.). A. P. was funded by his faculty baseline support and Office for Competitive Research Funds from the King Abdullah University of Science and Technology.
PubMed Central IDPMC3545754
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