Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages
Adeline C Y Chua, Jessica Jie Ying Ong, Benoit Malleret, Rossarin Suwanarusk, Varakorn Kosaisavee, Anne-Marie Zeeman, Caitlin A Cooper, Kevin S W Tan, Rou Zhang, Bee Huat Tan, Siti Nurdiana Abas, Andy Yip, Anne Elliot, Chester J Joyner, Jee Sun Cho, Kate Breyer, Szczepan Baran, Amber Lange, Steven P Maher, François Nosten, Christophe Bodenreider, Bryan K S Yeung, Dominique Mazier, Mary R Galinski, Nathalie Dereuddre-Bosquet, Roger Le Grand, Clemens H M Kocken, Laurent Rénia, Dennis E Kyle, Thierry T Diagana, Georges Snounou, Bruce Russell, Pablo Bifani, Adeline C Y Chua, Jessica Jie Ying Ong, Benoit Malleret, Rossarin Suwanarusk, Varakorn Kosaisavee, Anne-Marie Zeeman, Caitlin A Cooper, Kevin S W Tan, Rou Zhang, Bee Huat Tan, Siti Nurdiana Abas, Andy Yip, Anne Elliot, Chester J Joyner, Jee Sun Cho, Kate Breyer, Szczepan Baran, Amber Lange, Steven P Maher, François Nosten, Christophe Bodenreider, Bryan K S Yeung, Dominique Mazier, Mary R Galinski, Nathalie Dereuddre-Bosquet, Roger Le Grand, Clemens H M Kocken, Laurent Rénia, Dennis E Kyle, Thierry T Diagana, Georges Snounou, Bruce Russell, Pablo Bifani
Abstract
The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax, the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi, a macaque-infecting species phylogenetically close to P. vivax, was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax. We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti-P. vivax drug discovery efforts.
Conflict of interest statement
A.C.Y.C., J.J.Y.O., B.H.T., S.N.A., A.Y., K.B., S.B., A.L., C.B., B.K.S.Y., T.T.D. and P.B were/are employed by and/or shareholders of Novartis Pharma AG. The remaining authors declare no competing interests.
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