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An apicoplast-resident folate transporter is essential for sporogony of malaria parasites.

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posted on 2020-12-11, 13:37 authored by Francois Korbmacher, Benjamin Drepper, Theo Sanderson, Peer Martin, Thomas Stach, Alexander G Maier, Kai Matuschewski, Joachim M Matz
Malaria parasites are fast replicating unicellular organisms and require substantial amounts of folate for DNA synthesis. Despite the central role of this critical co-factor for parasite survival, only little is known about intraparasitic folate trafficking in Plasmodium. Here, we report on the expression, subcellular localisation and function of the parasite's folate transporter 2 (FT2) during life cycle progression in the murine malaria parasite Plasmodium berghei. Using live fluorescence microscopy of genetically engineered parasites, we demonstrate that FT2 localizes to the apicoplast. In invasive P. berghei stages, a fraction of FT2 is also observed at the apical end. Upon genetic disruption of FT2, blood and liver infection, gametocyte production, and mosquito colonisation remain unaltered. But in the Anopheles vector, FT2-deficient parasites develop inflated oocysts with unusual pulp formation consisting of numerous single-membrane vesicles, which ultimately fuse to form large cavities. Ultrastructural analysis suggests that this defect reflects aberrant sporoblast formation caused by abnormal vesicular traffic. Complete sporogony in FT2-deficient oocysts is very rare, and mutant sporozoites fail to establish hepatocyte infection, resulting in a complete block of parasite transmission. Our findings reveal a previously unrecognized organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector. This article is protected by copyright. All rights reserved.


Crick (Grant ID: 10043, Grant title: Blackman FC001043) Wellcome Trust (Grant ID: 210918, Grant title: WT 210918)


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