Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes.

Authors:
Moon RW1, Hall J, Rangkuti F, Ho YS, Almond N, Mitchell GH, Pain A, Holder AA, Blackman MJ.
In:
Source: Proc Natl Acad Sci USA
Publication Date: (2013)
Issue: 8: 531(6)
Research Area:
Parasitology
Basic Research
Cells used in publication:
Plasmodium knowlesi
Species: baboon
Tissue Origin:
Platform:
4D-Nucleofector® X-Unit
Experiment
Transfection of P. knowlesi. Tightly synchronized mature schizonts were purified by centrifugation over a Nycodenz cushion. ransfections were carried out using the Amaxa 4D electroporator (Lonza) and the P3 Primary cell 4D Nucleofector X Kit L (Lonza). For each transfection, DNA (20 µg) was dissolved in 10 µL TE (10 mM Tris•HCl, 1 mM EDTA, pH 8.0), then 100 µL of supplemented P3 primary cell solution added. Approximately 5–10 µL of schizonts (~5 × 107–108) were resuspended in the DNA plus P3 primary cell solution and immediately electroporated in a 4D Nucleofector X Kit L cuvette (Lonza) using program FP158. Electroporated parasites were transferred to a 1.4-mL Eppendorf tube containing 500 µL prewarmed complete medium plus 150 µL fresh RBC, and incubated at 37 °C on a thermomixer, shaking at 650 rpm while further transfections were carried out. After 30–40 min, transfected parasites were transferred to wells of a six-well plate, each containing 4.5 mL warm complete medium.
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.