Stearoyl-CoA desaturase regulates organelle biogenesis and hepatic merozoite formation in Plasmodium berghei.
Plasmodium
live attenuated parasite
liver stage
malaria
sporozoite
stearoyl-CoA Δ9-desaturase
vaccine
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
28 Feb 2024
28 Feb 2024
Historique:
revised:
13
02
2024
received:
14
08
2023
accepted:
16
02
2024
medline:
29
2
2024
pubmed:
29
2
2024
entrez:
29
2
2024
Statut:
aheadofprint
Résumé
Plasmodium is an obligate intracellular parasite that requires intense lipid synthesis for membrane biogenesis and survival. One of the principal membrane components is oleic acid, which is needed to maintain the membrane's biophysical properties and fluidity. The malaria parasite can modify fatty acids, and stearoyl-CoA Δ9-desaturase (Scd) is an enzyme that catalyzes the synthesis of oleic acid by desaturation of stearic acid. Scd is dispensable in P. falciparum blood stages; however, its role in mosquito and liver stages remains unknown. We show that P. berghei Scd localizes to the ER in the blood and liver stages. Disruption of Scd in the rodent malaria parasite P. berghei did not affect parasite blood stage propagation, mosquito stage development, or early liver-stage development. However, when Scd KO sporozoites were inoculated intravenously or by mosquito bite into mice, they failed to initiate blood-stage infection. Immunofluorescence analysis revealed that organelle biogenesis was impaired and merozoite formation was abolished, which initiates blood-stage infections. Genetic complementation of the KO parasites restored merozoite formation to a level similar to that of WT parasites. Mice immunized with Scd KO sporozoites confer long-lasting sterile protection against infectious sporozoite challenge. Thus, the Scd KO parasite is an appealing candidate for inducing protective pre-erythrocytic immunity and hence its utility as a GAP.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : BT/RLF/Re-entry/20/2012
Organisme : Science and Engineering Research Board
ID : CRG/2022/003848
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Aly, A.S.I., Mikolajczak, S.A., Rivera, H.S., Camargo, N., Jacobs-Lorena, V., Labaied, M. et al. (2008) Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection. Molecular Microbiology, 69, 152-163.
Amiar, S., Katris, N.J., Berry, L., Dass, S., Duley, S., Arnold, C.-S. et al. (2020) Division and adaptation to host environment of apicomplexan parasites depend on Apicoplast lipid metabolic plasticity and host organelle remodeling. Cell Reports, 30, 3778-3792.e9.
Amiar, S., MacRae, J.I., Callahan, D.L., Dubois, D., van Dooren, G.G., Shears, M.J. et al. (2016) Apicoplast-localized lysophosphatidic acid precursor assembly is required for bulk phospholipid synthesis in toxoplasma gondii and relies on an algal/plant-like glycerol 3-phosphate acyltransferase. PLoS Pathogens, 12, e1005765.
Baer, K., Klotz, C., Kappe, S.H.I.I., Schnieder, T. & Frevert, U. (2007) Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature. PLoS Pathogens, 3, 1651-1668.
Botté, C.Y., Yamaryo-Botté, Y., Rupasinghe, T.W.T., Mullin, K.A., MacRae, J.I., Spurck, T.P. et al. (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, 7506-7511.
Brancucci, N.M.B., Gerdt, J.P., Wang, C., De Niz, M., Philip, N., Adapa, S.R. et al. (2017) Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell, 171, 1532-1544.e15.
Bruña-Romero, O., Hafalla, J.C., González-Aseguinolaza, G., Sano, G., Tsuji, M. & Zavala, F. (2001) Detection of malaria liver-stages in mice infected through the bite of a single Anopheles mosquito using a highly sensitive real-time PCR. International Journal for Parasitology, 31, 1499-1502.
Butler, N.S., Schmidt, N.W., Vaughan, A.M., Aly, A.S., Kappe, S.H.I.I. & Harty, J.T. (2011) Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites. Cell Host & Microbe, 9, 451-462.
Choudhary, H.H., Gupta, R. & Mishra, S. (2019) PKAc is not required for the preerythrocytic stages of Plasmodium berghei. Life Science Alliance, 2, 1-11.
Daily, J.P., Scanfeld, D., Pochet, N., Le Roch, K., Plouffe, D., Kamal, M. et al. (2007) Distinct physiological states of Plasmodium falciparum in malaria-infected patients. Nature, 450, 1091-1095.
Dankwa, D.A., Davis, M.J., Kappe, S.H.I. & Vaughan, A.M. (2016) A Plasmodium yoelii Mei2-like RNA binding protein is essential for completion of liver stage schizogony. Infection and Immunity, 84, 1336-1345.
Déchamps, S., Wengelnik, K., Berry-Sterkers, L., Cerdan, R., Vial, H.J. & Gannoun-Zaki, L. (2010) The Kennedy phospholipid biosynthesis pathways are refractory to genetic disruption in Plasmodium berghei and therefore appear essential in blood stages. Molecular and Biochemical Parasitology, 173, 69-80.
Dubois, D., Fernandes, S., Amiar, S., Dass, S., Katris, N.J., Botté, C.Y. et al. (2018) Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages. Journal of Lipid Research, 59, 994-1004.
Duffy, P.E. (2022) Current approaches to malaria vaccines. Current Opinion in Microbiology, 70, 102227.
Epstein, J.E., Tewari, K., Lyke, K.E., Sim, B.K.L., Billingsley, P.F., Laurens, M.B. et al. (2011) Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity. Science, 334, 475-480.
Gallagher, J.R. & Prigge, S.T. (2010) Plasmodium falciparum acyl carrier protein crystal structures in disulfide-linked and reduced states and their prevalence during blood stage growth. Proteins, 78, 575-588.
Gerold, P., Schofield, L., Blackman, M.J., Holder, A.A. & Schwarz, R.T. (1996) Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum. Molecular and Biochemical Parasitology, 75, 131-143.
Gratraud, P., Huws, E., Falkard, B., Adjalley, S., Fidock, D.A., Berry, L. et al. (2009) Oleic acid biosynthesis in Plasmodium falciparum: characterization of the stearoyl-CoA desaturase and investigation as a potential therapeutic target. PLoS One, 4, e6889.
Grellier, P., Rigomier, D., Clavey, V., Fruchart, J.C. & Schrevel, J. (1991) Lipid traffic between high density lipoproteins and Plasmodium falciparum-infected red blood cells. The Journal of Cell Biology, 112, 267-277.
Holder, A.A. & Freeman, R.R. (1981) Immunization against blood-stage rodent malaria using purified parasite antigens. Nature, 294, 361-364.
Ishino, T., Boisson, B., Orito, B.B., Lacroix, C., Bischoff, E., Loussert, C. et al. (2009) LISP1 is important for the egress of Plasmodium berghei parasites from liver cells. Cellular Microbiology, 11, 1329-1339.
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, 346-356.
Khan, S.M., Janse, C.J., Kappe, S.H.I. & Mikolajczak, S.A. (2012) Genetic engineering of attenuated malaria parasites for vaccination. Current Opinion in Biotechnology, 23, 908-916. Available from: https://doi.org/10.1016/j.copbio.2012.04.003
Kloehn, J., Oppenheim, R.D., Siddiqui, G., De Bock, P.-J., Kumar Dogga, S., Coute, Y. et al. (2020) Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii. BMC Biology, 18, 67.
Krishnan, A., Kloehn, J., Lunghi, M., Chiappino-Pepe, A., Waldman, B.S., Nicolas, D. et al. (2020) Functional and computational genomics reveal unprecedented flexibility in stage-specific toxoplasma metabolism. Cell Host & Microbe, 27, 290-306.e11.
Krishnegowda, G. & Gowda, D.C. (2003) Intraerythrocytic Plasmodium falciparum incorporates extraneous fatty acids to its lipids without any structural modification. Molecular and Biochemical Parasitology, 132, 55-58.
Liang, X., Cui, J., Yang, X., Xia, N., Li, Y., Zhao, J. et al. (2020) Acquisition of exogenous fatty acids renders apicoplast-based biosynthesis dispensable in tachyzoites of toxoplasma. The Journal of Biological Chemistry, 295, 7743-7752.
Lindner, S.E., Mikolajczak, S.A., Vaughan, A.M., Moon, W., Joyce, B.R., Sullivan, W.J. et al. (2013) Perturbations of PlasmodiumPuf2 expression and RNA-seq of Puf2-deficient sporozoites reveal a critical role in maintaining RNA homeostasis and parasite transmissibility. Cellular Microbiology, 15, 1266-1283.
Lindner, S.E., Miller, J.L. & Kappe, S.H.I. (2012) Malaria parasite pre-erythrocytic infection: preparation meets opportunity. Cellular Microbiology, 14, 316-324.
Lindner, S.E., Sartain, M.J., Hayes, K., Harupa, A., Moritz, R.L., Kappe, S.H.I. et al. (2014) Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver-stage development. Molecular Microbiology, 91, 679-693.
Marrakchi, H., Zhang, Y.M. & Rock, C.O. (2002) Mechanistic diversity and regulation of type II fatty acid synthesis. Biochemical Society Transactions, 30, 1050-1055.
Mazumdar, J. & Striepen, B. (2007) Make it or take it: fatty acid metabolism of apicomplexan parasites. Eukaryotic Cell, 6, 1727-1735.
Mazumdar, J., Wilson, E.H., Masek, K., Hunter, C.A. & Striepen, B. (2006) Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proceedings of the National Academy of Sciences of the United States of America, 103, 13192-13197.
Mi-Ichi, F., Kano, S. & Mitamura, T. (2007) Oleic acid is indispensable for intraerythrocytic proliferation of Plasmodium falciparum. Parasitology, 134, 1671-1677.
Mi-Ichi, F., Kita, K. & Mitamura, T. (2006) Intraerythrocytic Plasmodium falciparum utilize a broad range of serum-derived fatty acids with limited modification for their growth. Parasitology, 133, 399-410.
Mikolajczak, S.A., Jacobs-Lorena, V., MacKellar, D.C., Camargo, N. & Kappe, S.H.I. (2007) L-FABP is a critical host factor for successful malaria liver stage development. International Journal for Parasitology, 37, 483-489.
Miyazaki, M., Kim, Y.C. & Ntambi, J.M. (2001) A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. Journal of Lipid Research, 42, 1018-1024.
Mordmüller, B., Surat, G., Lagler, H., Chakravarty, S., Ishizuka, A.S., Lalremruata, A. et al. (2017) Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature, 542, 445-449. Available from: https://doi.org/10.1038/nature21060
Mueller, A.K., Camargo, N., Kaiser, K., Andorfer, C., Frevert, U., Matuschewski, K. et al. (2005) Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface. Proceedings of the National Academy of Sciences of the United States of America, 102, 3022-3027.
Mueller, A.-K., Labaied, M., Kappe, S.H.I. & Matuschewski, K. (2005) Genetically modified plasmodium parasites as a protective experimental malaria vaccine. Nature, 433, 164-167.
Murphy, S.C., Vaughan, A.M., Kublin, J.G., Fishbauger, M., Seilie, A.M., Cruz, K.P. et al. (2022) A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection. Science Translational Medicine, 14, eabn9709.
Narwal, S.K., Nayak, B., Mehra, P. & Mishra, S. (2022) Protein kinase 9 is not required for completion of the Plasmodium berghei life cycle. Microbiological Research, 260, 127051.
Nganou-Makamdop, K. & Sauerwein, R.W. (2013) Liver or blood-stage arrest during malaria sporozoite immunization: the later the better? Trends in Parasitology, 29, 304-310. Available from: https://doi.org/10.1016/j.pt.2013.03.008
Nussenzweig, R.S., Vanderberg, J., Most, H. & Orton, C. (1967) Protective immunity produced by the injection of x-irradiated sporozoites of Plasmodium berghei. Nature, 216, 160-162.
Ofulla, A.V., Okoye, V.C., Khan, B., Githure, J.I., Roberts, C.R., Johnson, A.J. et al. (1993) Cultivation of plasmodium falciparum parasites in a serum-free medium. The American Journal of Tropical Medicine and Hygiene, 49, 335-340.
Overstreet, M.G., Cockburn, I.A., Chen, Y.C. & Zavala, F. (2008) Protective CD8+ T cells against plasmodium liver stages: immunobiology of an “unnatural” immune response. Immunological Reviews, 225, 272-283.
Palacpac, N.M.Q., Leung, B.W.Y., Arisue, N., Tanabe, K., Sattabongkot, J., Tsuboi, T. et al. (2006) Plasmodium vivax serine repeat antigen (SERA) multigene family exhibits similar expression patterns in independent infections. Molecular and Biochemical Parasitology, 150, 353-358.
Pei, Y., Tarun, A.S., Vaughan, A.M., Herman, R.W., Soliman, J.M.B.B., Erickson-Wayman, A. et al. (2010) Plasmodium pyruvate dehydrogenase activity is only essential for the parasite's progression from liver infection to blood infection. Molecular Microbiology, 75, 957-971.
Prudêncio, M., Rodriguez, A. & Mota, M.M. (2006) The silent path to thousands of merozoites: the plasmodium liver stage. Nature Reviews. Microbiology, 4, 849-856.
Ralph, S.A., van Dooren, G.G., Waller, R.F., Crawford, M.J., Fraunholz, M.J., Foth, B.J. et al. (2004) Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast. Nature Reviews. Microbiology, 2, 203-216.
Ramakrishnan, S., Docampo, M.D., MacRae, J.I., Pujol, F.M., Brooks, C.F., van Dooren, G.G. et al. (2012) Apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in apicomplexan parasite Toxoplasma gondii. The Journal of Biological Chemistry, 287, 4957-4971.
Ramakrishnan, S., Docampo, M.D., MacRae, J.I., Ralton, J.E., Rupasinghe, T., McConville, M.J. et al. (2015) The intracellular parasite Toxoplasma gondii depends on the synthesis of long-chain and very long-chain unsaturated fatty acids not supplied by the host cell. Molecular Microbiology, 97, 64-76.
Ramakrishnan, S., Serricchio, M., Striepen, B. & Bütikofer, P. (2013) Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans. Progress in Lipid Research, 52, 488-512.
Ramaprasad, A., Burda, P.-C., Calvani, E., Sait, A.J., Palma-Duran, S.A., Withers-Martinez, C. et al. (2022) A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite. eLife, 11, e82207.
Rénia, L., Miltgen, F., Charoenvit, Y., Ponnudurai, T., Verhave, J.P., Collins, W.E. et al. (1988) Malaria sporozoite penetration a new approach by double staining. Journal of Immunological Methods, 112, 201-205.
Rosenberg, R., Wirtz, R.A., Schneider, I. & Burge, R. (1990) An estimation of the number of malaria sporozoites ejected by a feeding mosquito. Transactions of the Royal Society of Tropical Medicine and Hygiene, 84, 209-212.
Seder, R.A., Chang, L.-J.J., Enama, M.E., Zephir, K.L., Sarwar, U.N., Gordon, I.J. et al. (2013) Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science (80- ), 341, 1359-1365.
Shanklin, J., Whittle, E. & Fox, B.G. (1994) Eight histidine residues are catalytically essential in a membrane-associated iron enzyme, stearoyl-CoA desaturase, and are conserved in alkane hydroxylase and xylene monooxygenase. Biochemistry, 33, 12787-12794.
Shears, M.J., Botté, C.Y. & McFadden, G.I. (2015) Fatty acid metabolism in the plasmodium apicoplast: drugs, doubts and knockouts. Molecular and Biochemical Parasitology, 199, 34-50. Available from: https://doi.org/10.1016/j.molbiopara.2015.03.004
Sheokand, P.K., Yamaryo-Botté, Y., Narwal, M., Arnold, C.-S., Thakur, V., Islam, M.M. et al. (2023) A Plasmodium falciparum lysophospholipase regulates host fatty acid flux via parasite lipid storage to enable controlled asexual schizogony. Cell Reports, 42, 112251.
Shimizu, S., Osada, Y., Kanazawa, T., Tanaka, Y. & Arai, M. (2010) Suppressive effect of azithromycin on Plasmodium berghei mosquito stage development and apicoplast replication. Malaria Journal, 9, 73.
Shunmugam, S., Arnold, C.-S., Dass, S., Katris, N.J. & Botté, C.Y. (2022) The flexibility of Apicomplexa parasites in lipid metabolism. PLoS Pathogens, 18, e1010313.
Srivastava, P.N. & Mishra, S. (2022) Disrupting a Plasmodium berghei putative phospholipase impairs efficient egress of merosomes. International Journal for Parasitology, 52, 547-558. Available from: https://doi.org/10.1016/j.ijpara.2022.03.002
Stanway, R.R., Bushell, E., Chiappino-Pepe, A., Roques, M., Sanderson, T., Franke-Fayard, B. et al. (2019) Genome-scale identification of essential metabolic processes for targeting the plasmodium liver stage. Cell, 179, 1112-1128.e26.
Sturm, A., Amino, R., Van De Sand, C., Regen, T., Retzlaff, S., Rennenberg, A. et al. (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science (80- ), 313, 1287-1290.
Tarun, A.S., Vaughan, A.M. & Kappe, S.H.I. (2009) Redefining the role of de novo fatty acid synthesis in Plasmodium parasites. Trends in Parasitology, 25, 545-550.
van Dooren, G.G. & Striepen, B. (2013) The algal past and parasite present of the apicoplast. Annual Review of Microbiology, 67, 271-289.
van Schaijk, B.C.L., Kumar, T.R.S., Vos, M.W., Richman, A., van Gemert, G.-J., Li, T. et al. (2014) Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of anopheles mosquitoes. Eukaryotic Cell, 13, 550-559.
Vaughan, A.M., O'Neill, M.T., Tarun, A.S., Camargo, N., Phuong, T.M., Aly, A.S.I.I. et al. (2009) Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cellular Microbiology, 11, 506-520.
Waller, R.F., Ralph, S.A., Reed, M.B., Su, V., Douglas, J.D., Minnikin, D.E. et al. (2003) A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 47, 297-301.
Walsh, D., Katris, N.J., Sheiner, L. & Botté, C.Y. (2022) Toxoplasma metabolic flexibility in different growth conditions. Trends in Parasitology, 38, 775-790.
Wein, S., Ghezal, S., Buré, C., Maynadier, M., Périgaud, C., Vial, H.J. et al. (2018) Contribution of the precursors and interplay of the pathways in the phospholipid metabolism of the malaria parasite. Journal of Lipid Research, 59, 1461-1471.
World Malaria Report, 2022. (2022).
Yoshida, N., Nussenzweig, R.S., Potocnjak, P., Nussenzweig, V. & Aikawa, M. (1980) Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite. Science (80- ), 207, 71-73.
Yu, M., Kumar, T.R.S., Nkrumah, L.J., Coppi, A., Retzlaff, S., Li, C.D. et al. (2008) The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. Cell Host & Microbe, 4, 567-578.
Zavala, F. (2022) RTS,S: the first malaria vaccine. The Journal of Clinical Investigation, 132, e156588.
Zhang, M., Wang, C., Otto, T.D., Oberstaller, J., Liao, X., Adapa, S.R. et al. (2018) Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science, 360, eaap7847.