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An apicoplast-resident folate transporter is essential for sporogony of malaria parasites.
- Source :
-
Cellular microbiology [Cell Microbiol] 2021 Jan; Vol. 23 (1), pp. e13266. Date of Electronic Publication: 2020 Oct 08. - Publication Year :
- 2021
-
Abstract
- 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 localises 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 unrecognised organellar folate transporter that exerts critical roles for pathogen maturation in the arthropod vector.<br /> (© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Anopheles parasitology
Hepatocytes parasitology
Life Cycle Stages
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Mosquito Vectors
Oocysts cytology
Oocysts genetics
Oocysts metabolism
Organisms, Genetically Modified
Plasmodium berghei cytology
Protozoan Proteins metabolism
Sporozoites metabolism
Apicoplasts metabolism
Folic Acid metabolism
Folic Acid Transporters genetics
Folic Acid Transporters metabolism
Malaria parasitology
Plasmodium berghei genetics
Plasmodium berghei metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1462-5822
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 32975363
- Full Text :
- https://doi.org/10.1111/cmi.13266