Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages

Chua, Adeline C. Y.; Ong, Jessica Jie Ying; Malleret, Benoît; Suwanarusk, Rossarin; Kosaisavee, Varakorn; Zeeman, Anne‐Marie; Cooper, Caitlin; Tan, Kevin S. W.; Zhang, Rou; Tan, Bee Huat; Abas, Siti Nurdiana; Yip, Andy M.; Elliot, Anne; Joyner, Chester J.; Cho, Jee Sun; Breyer, Kate; Baran, Szczepan W.; Lange, Amber; Maher, Steven P.; Nosten, François; Bodenreider, Christophe; Yeung, Bryan K. S.; Mazier, Dominique; Galinski, Mary R.; Dereuddre‐Bosquet, Nathalie; Grand, Roger Le; Kocken, Clemens H. M.; Rénia, Laurent; Kyle, Dennis E.; Diagana, Thierry T.; Snounou, Georges; Russell, Bruce; Bifani, Pablo

doi:10.1038/s41467-019-11332-4

Cited by 45 publications

(53 citation statements)

References 60 publications

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“…Such an approach could also make use of the Saimiri and Aotus nonhuman primate model-as both species can be infected by P. vivax, while PvDBP can bind only to Aotus erythrocytes and not to Saimiri ones, indicating an alternative invasion pathway reminiscent of what is observed for Duffy-negative human erythrocytes [90]. Alternative models to decipher erythrocyte invasion mechanisms could also rely on the genetically tractable P. knowlesi that shares many biological similarities with P. vivax, including the requirement of the Duffy receptor for erythrocyte invasion [91] or even on P. cynomolgi, closely related to P. vivax and recently adapted to in vitro culture [92].…”

Section: Future Directions and Conclusive Remarksmentioning

confidence: 99%

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

2020

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The absence of the Duffy protein at the surface of erythrocytes was considered for decades to confer full protection against Plasmodium vivax as this blood group is the receptor for the key parasite ligand P. vivax Duffy binding protein (PvDBP). However, it is now clear that the parasite is able to break through this protection and induce clinical malaria in Duffy-negative people, although the underlying mechanisms are still not understood. Here, we briefly review the evidence of Duffy-negative infections by P. vivax and summarize the current hypothesis at the basis of this invasion process. We discuss those in the perspective of malaria-elimination challenges, notably in African countries.

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Section: Future Directions and Conclusive Remarksmentioning

confidence: 99%

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

2020

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“…Currently P. falciparum, P. knowlesi and P. cynomolgi are the only Plasmodium spp . that can be cultured in vitro [4-7], and to study these time-dependent changes in culture, the synchrony of the parasites needs to be artificially maintained. Whilst parasites remain synchronous in vivo [8-10], the absence of host interactions that regulate the synchrony of parasite development in vitro [8, 11] cause the parasites in the culture to become asynchronous – driven by small differences in the length of the replication cycle between individual parasites.…”

Section: Introductionmentioning

confidence: 99%

Use of a highly specific kinase inhibitor for rapid, simple and precise synchronization ofPlasmodium falciparumandPlasmodium knowlesiasexual stage parasites

Ressurreição

Thomas

Nofal

et al. 2020

Preprint

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During the course of the asexual erythrocytic stage of development, Plasmodium spp. parasites undergo a series of morphological changes and induce alterations in the host cell. At the end of this stage, the parasites exit the host cell, after which the progeny invade a new host cell. These processes are rapid and occur in a time-dependent manner. Of particular importance, egress and invasion of erythrocytes by the parasite are difficult to capture in an unsynchronized culture, or even a culture that has been synchronized to within hours. Therefore, precise synchronization of parasite cultures is of paramount importance for the investigation of these processes. Here we describe a method for synchronizing Plasmodium falciparum and Plasmodium knowlesi asexual blood stage parasites with ML10, a highly specific inhibitor of the cGMP-dependent protein kinase (PKG) that arrests parasite growth approximately 15 minutes prior to egress. This inhibitor allows parasite cultures to be synchronized to within minutes, with a simple wash step. Furthermore, we show that parasites remain viable for several hours after becoming arrested by the compound and that ML10 has advantages over the previously used PKG inhibitor Compound 2. Here, we demonstrate that ML10 is an invaluable tool for the study of Plasmodium spp. asexual blood stage biology and for the routine synchronization of P. falciparum and P. knowlesi cultures.

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“…Breakthroughs in culturing P. cynomolgi blood-stage parasites are on the horizon [160] and these have provided glimmers of hope in relation to expansion of use of this model species, particularly to advance research on liver-stage biology and the identification of drug targets and novel interventions. The Bill and Melinda Gates Foundation has taken notice and recently supported a meeting of experts who are advancing this line of research [125].…”

Section: Introductionmentioning

confidence: 99%

Functional genomics of simian malaria parasites and host–parasite interactions

Galinski

2019

Briefings in Functional Genomics

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Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host–parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host–parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.

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Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages

Cited by 45 publications

References 60 publications

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals

Use of a highly specific kinase inhibitor for rapid, simple and precise synchronization ofPlasmodium falciparumandPlasmodium knowlesiasexual stage parasites

Functional genomics of simian malaria parasites and host–parasite interactions

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