title: Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes.
abstract: Research 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.
authors.affiliation: Division of Parasitology,  Medical Research Council National Institute for Medical Research, London NW7 1AA,  United Kingdom.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Moon
authors.forename: Joanna
authors.initials: J
authors.lastname: Hall
authors.forename: Farania
authors.initials: F
authors.lastname: Rangkuti
authors.forename: Yung Shwen
authors.initials: YS
authors.lastname: Ho
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Graham H
authors.initials: GH
authors.lastname: Mitchell
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blackman
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015925:Cryopreservation; D046508:Culture Techniques / Q000379:methods*; D017931:DNA Primers / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology*; D005838:Genotype; D006801:Humans; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D016790:Plasmodium knowlesi / Q000235:genetics* / Q000254:growth & development*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D017931:DNA Primers