An apicoplast-resident folate transporter is essential for sporogony of malaria parasites.
Animals
Anopheles
/ parasitology
Apicoplasts
/ metabolism
Folic Acid
/ metabolism
Folic Acid Transporters
/ genetics
Hepatocytes
/ parasitology
Life Cycle Stages
Malaria
/ parasitology
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Mosquito Vectors
Oocysts
/ cytology
Organisms, Genetically Modified
Plasmodium berghei
/ cytology
Protozoan Proteins
/ metabolism
Sporozoites
/ metabolism
Plasmodium
apicoplast
folate
malaria
membrane transport protein
sporogony
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
04
04
2020
revised:
14
08
2020
accepted:
18
09
2020
pubmed:
26
9
2020
medline:
21
10
2021
entrez:
25
9
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Folic Acid Transporters
0
Protozoan Proteins
0
Folic Acid
935E97BOY8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13266Subventions
Organisme : Wellcome Trust
ID : 210918/Z/18/Z
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
Références
Aly, A. S., & Matuschewski, K. (2005). A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocysts. The Journal of Experimental Medicine, 202(2), 225-230.
Botté, C. Y., Yamaryo-Botte, Y., Rupasinghe, T. W., Mullin, K. A., MacRae, J. I., Spurck, T. P., … McFadden, G. I. (2013). Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites. Proceedings of the National Academy of Sciences of the United States of America, 110(18), 7506-7511.
Bray, R. S., Burgess, R. W., Fox, R. M., & Miller, M. J. (1959). Effect of pyrimethamine upon sporogony and pre-erythrocytic schizogony of Laverania falciparum. Bulletin of the World Health Organization, 21, 233-238.
Burda, P. C., Schaffner, M., Kaiser, G., Roques, M., Zuber, B., & Heussler, V. T. (2017). A Plasmodium plasma membrane reporter reveals membrane dynamics by live-cell microscopy. Scientific Reports, 7(1), 9740.
Bushell, E., Gomes, A. R., Sanderson, T., Anar, B., Girling, G., Herd, C., … Billker, O. (2017). Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell, 170(2), 260-272.
Doberstyn, E. B., Hall, A. P., Vetvutanapibul, K., & Sonkon, P. (1976). Single-dose therapy of falciparum malaria using pyrimethamine in combination with diformyldapsone or sulfadoxine. The American Journal of Tropical Medicine and Hygiene, 25(1), 14-19.
Esu, E. B., Oringanje, C., & Meremikwu, M. M. (2019). Intermittent preventive treatment for malaria in infants. Cochrane Database of Systematic Reviews, 12, CD011525.
Foth, B. J., Ralph, S. A., Tonkin, C. J., Struck, N. S., Fraunholz, M., Roos, D. S., … McFadden, G. I. (2003). Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science, 299(5607), 705-708.
Friesen, J., Borrmann, S., & Matuschewski, K. (2011). Induction of antimalaria immunity by pyrimethamine prophylaxis during exposure to sporozoites is curtailed by parasite resistance. Antimicrobial Agents and Chemotherapy, 55(6), 2760-2767.
Frischknecht, F., & Matuschewski, K. (2017). Plasmodium sporozoite biology. Cold Spring Harbor Perspectives in Medicine, 7(5), a025478.
Guindon, S., Dufayard, J. F., Lefort, V., Anisimova, M., Hordijk, W., & Gascuel, O. (2010). New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0. Systematic Biology, 59(3), 307-321.
Hanson, A. D., & Gregory, J. F., 3rd. (2011). Folate biosynthesis, turnover, and transport in plants. Annual Review of Plant Biology, 62, 105-125.
Harinasuta, T., Viravan, C., & Reid, H. A. (1967). Sulphormethoxine in chloroquine-resistant falciparum malaria in Thailand. Lancet, 1(7500), 1117-1119.
Janse, C. J., Franke-Fayard, B., Mair, G. R., Ramesar, J., Thiel, C., Engelmann, S., … Waters, A. P. (2006). High efficiency transfection of Plasmodium berghei facilitates novel selection procedures. Molecular and Biochemical Parasitology, 145(1), 60-70.
Janse, C. J., Ramesar, J., & Waters, A. P. (2006). High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei. Nature Protocols, 1(1), 346-356.
Jiang, D., Zhao, Y., Wang, X., Fan, J., Heng, J., Liu, X., … Zhang, X. C. (2013). Structure of the YajR transporter suggests a transport mechanism based on the conserved motif a. Proceedings of the National Academy of Sciences of the United States of America, 110(36), 14664-14669.
Katoh, K., & Standley, D. M. (2013). MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Molecular Biology and Evolution, 30(4), 772-780.
Kennedy, K., Cobbold, S. A., Hanssen, E., Birnbaum, J., Spillman, N. J., McHugh, E., … Ralph, S. A. (2019). Delayed death in the malaria parasite Plasmodium falciparum is caused by disruption of prenylation-dependent intracellular trafficking. PLoS Biology, 17(7), e3000376.
Kenthirapalan, S., Waters, A. P., Matuschewski, K., & Kooij, T. W. (2012). Flow cytometry-assisted rapid isolation of recombinant Plasmodium berghei parasites exemplified by functional analysis of aquaglyceroporin. International Journal for Parasitology, 42(13-14), 1185-1192.
Klaus, S. M., Kunji, E. R., Bozzo, G. G., Noiriel, A., de la Garza, R. D., Basset, G. J., … Hanson, A. D. (2005). Higher plant plastids and cyanobacteria have folate carriers related to those of trypanosomatids. The Journal of Biological Chemistry, 280(46), 38457-38463.
Kone, A., van de Vegte-Bolmer, M., Siebelink-Stoter, R., van Gemert, G. J., Dara, A., Niangaly, H., … Djimde, A. A. (2010). Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival. International Journal for Parasitology, 40(10), 1221-1228.
Kooij, T. W., Rauch, M. M., & Matuschewski, K. (2012). Expansion of experimental genetics approaches for Plasmodium berghei with versatile transfection vectors. Molecular and Biochemical Parasitology, 185(1), 19-26.
Lemley, C., Yan, S., Dole, V. S., Madhubala, R., Cunningham, M. L., Beverley, S. M., … Stuart, K. D. (1999). The Leishmania donovani LD1 locus gene ORFG encodes a biopterin transporter (BT1). Molecular and Biochemical Parasitology, 104(1), 93-105.
Lim, L., Sayers, C. P., Goodman, C. D., & McFadden, G. I. (2016). Targeting of a transporter to the outer apicoplast membrane in the human malaria parasite Plasmodium falciparum. PLoS One, 11(7), e0159603.
Matz, J. M., Goosmann, C., Matuschewski, K., & Kooij, T. W. A. (2018). An unusual prohibitin regulates malaria parasite mitochondrial membrane potential. Cell Reports, 23(3), 756-767.
Matz, J. M., & Kooij, T. W. (2015). Towards genome-wide experimental genetics in the in vivo malaria model parasite Plasmodium berghei. Pathogens and Global Health, 109(2), 46-60.
Matz, J. M., Matuschewski, K., & Kooij, T. W. (2013). Two putative protein export regulators promote Plasmodium blood stage development in vivo. Molecular and Biochemical Parasitology, 191(1), 44-52.
Matz, J. M., Watanabe, M., Falade, M., Tohge, T., Hoefgen, R., & Matuschewski, K. (2019). Plasmodium para-aminobenzoate synthesis and salvage resolve avoidance of folate competition and adaptation to host diet. Cell Reports, 26(2), 356-363.
Most, H., Herman, R., & Schoenfeld, C. (1967). Chemotherapy of sporozoite- and blood-induced Plasmodium berghei infections with selected antimalarial agents. The American Journal of Tropical Medicine and Hygiene, 16(5), 572-575.
Müller, I. B., & Hyde, J. E. (2013). Folate metabolism in human malaria parasites - 75 years on. Molecular and Biochemical Parasitology, 188(1), 63-77.
Mullin, K. A., Lim, L., Ralph, S. A., Spurck, T. P., Handman, E., & McFadden, G. I. (2006). Membrane transporters in the relict plastid of malaria parasites. Proceedings of the National Academy of Sciences of the United States of America, 103(25), 9572-9577.
Myler, P. J., Lodes, M. J., Merlin, G., de Vos, T., & Stuart, K. D. (1994). An amplified DNA element in Leishmania encodes potential integral membrane and nucleotide-binding proteins. Molecular and Biochemical Parasitology, 66(1), 11-20.
Nzila, A. (2006). The past, present and future of antifolates in the treatment of Plasmodium falciparum infection. The Journal of Antimicrobial Chemotherapy, 57(6), 1043-1054.
Orr, R. Y., Philip, N., & Waters, A. P. (2012). Improved negative selection protocol for Plasmodium berghei in the rodent malarial model. Malaria Journal, 11, 103.
Quinlivan, E. P., Roje, S., Basset, G., Shachar-Hill, Y., Gregory, J. F., 3rd, & Hanson, A. D. (2003). The folate precursor p-aminobenzoate is reversibly converted to its glucose ester in the plant cytosol. The Journal of Biological Chemistry, 278(23), 20731-20737.
Ralph, S. A., van Dooren, G. G., Waller, R. F., Crawford, M. J., Fraunholz, M. J., Foth, B. J., … McFadden, G. I. (2004). Tropical infectious diseases: Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nature Reviews. Microbiology, 2(3), 203-216.
Rathnapala, U. L., Goodman, C. D., & McFadden, G. I. (2017). A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite. PLoS Pathogens, 13(6), e1006396.
Salcedo-Sora, J. E., Ochong, E., Beveridge, S., Johnson, D., Nzila, A., Biagini, G. A., … Ward, S. A. (2011). The molecular basis of folate salvage in Plasmodium falciparum: Characterization of two folate transporters. The Journal of Biological Chemistry, 286(52), 44659-44668.
Sayers, C. P., Mollard, V., Buchanan, H. D., McFadden, G. I., & Goodman, C. D. (2018). A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites. Cellular Microbiology, 20(1), e12789.
Shute, P. G., & Maryon, M. (1954). The effect of pyrimethamine (daraprim) on the gametocytes and oocysts of Plasmodium falciparum and Plasmodium vivax. Transactions of the Royal Society of Tropical Medicine and Hygiene, 48(1), 50-63.
Sinden, R. E., & Strong, K. (1978). An ultrastructural study of the sporogonic development of Plasmodium falciparum in Anopheles gambiae. Transactions of the Royal Society of Tropical Medicine and Hygiene, 72(5), 477-491.
Sinden, R. E., Winger, L., Carter, E. H., Hartley, R. H., Tirawanchai, N., Davies, C. S., … Sluiters, J. F. (1987). Ookinete antigens of Plasmodium berghei: A light and electron-microscope immunogold study of expression of the 21 kDa determinant recognized by a transmission-blocking antibody. Proceedings of the Royal Society of London - Series B: Biological Sciences, 230(1261), 443-458.
Stanway, R. R., Bushell, E., Chiappino-Pepe, A., Roques, M., Sanderson, T., Franke-Fayard, B., … Heussler, V. T. (2019). Genome-scale identification of essential metabolic processes for targeting the Plasmodium liver stage. Cell, 179(5), 1112-1128.
Stanway, R. R., Witt, T., Zobiak, B., Aepfelbacher, M., & Heussler, V. T. (2009). GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites. Biology of the Cell, 101(7), 415-430.
Terzakis, J. A., Sprinz, H., & Ward, R. A. (1967). The transformation of the Plasmodium gallinaceum oocyst in Aedes aegypti mosquitoes. The Journal of Cell Biology, 34(1), 311-326.
Tibbetts, A. S., & Appling, D. R. (2010). Compartmentalization of mammalian folate-mediated one-carbon metabolism. Annual Review of Nutrition, 30, 57-81.
Tsuji, M., Mattei, D., Nussenzweig, R. S., Eichinger, D., & Zavala, F. (1994). Demonstration of heat-shock protein 70 in the sporozoite stage of malaria parasites. Parasitology Research, 80(1), 16-21.
van Dooren, G. G., Stimmler, L. M., & McFadden, G. I. (2006). Metabolic maps and functions of the Plasmodium mitochondrion. FEMS Microbiology Reviews, 30(4), 596-630.
van Dooren, G. G., Su, V., D'Ombrain, M. C., & McFadden, G. I. (2002). Processing of an apicoplast leader sequence in Plasmodium falciparum and the identification of a putative leader cleavage enzyme. The Journal of Biological Chemistry, 277(26), 23612-23619.
Vanderberg, J., Rdodin, J., & Yoeli, M. (1967). Electron microscopic and histochemical studies of sporozoite formation in Plasmodium berghei. The Journal of Protozoology, 14(1), 82-103.
Waller, R. F., Reed, M. B., Cowman, A. F., & McFadden, G. I. (2000). Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway. The EMBO Journal, 19(8), 1794-1802.
Yang, J., & Zhang, Y. (2015). I-TASSER server: New development for protein structure and function predictions. Nucleic Acids Research, 43(W1), W174-W181.
Yeh, E., & DeRisi, J. L. (2011). Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. PLoS Biology, 9(8), e1001138.
Zhang, M., Wang, C., Otto, T. D., Oberstaller, J., Liao, X., Adapa, S. R., … Adams, J. H. (2018). Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science, 360(6388), eaap7847.