Lipid analysis of Eimeria sporozoites reveals exclusive phospholipids, a phylogenetic mosaic of endogenous synthesis, and a host-independent lifestyle
| Autor: | Kong, Pengfei, Lehmann, Maik J, Helms, J Bernd, Brouwers, Jos F, Gupta, Nishith, dB&C FR-RMSC FR, LS Veterinaire biochemie, dB&C FR-RMSC RMSC, Dep Biochemie en Celbiologie, Sub MS-faciliteit |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apicoplast 030102 biochemistry & molecular biology lcsh:Cytology Endoplasmic reticulum Lipid metabolism Cell Biology Golgi apparatus Biology biology.organism_classification Biochemistry Eimeria Article Cell biology 03 medical and health sciences symbols.namesake 030104 developmental biology Lytic cycle Membrane biogenesis parasitic diseases Genetics symbols lcsh:QH573-671 Molecular Biology Biogenesis |
| Zdroj: | Cell Discovery Cell Discovery, Vol 4, Iss 1, Pp 1-17 (2018) Cell Discovery, 4. Nature Publishing Group |
| ISSN: | 2056-5968 |
| Popis: | Successful inter-host transmission of most apicomplexan parasites requires the formation of infective sporozoites within the oocysts. Unlike all other infective stages that are strictly intracellular and depend on host resources, the sporozoite stage develops outside the host cells, but little is known about its self-governing metabolism. This study deployed Eimeria falciformis, a parasite infecting the mouse as its natural host, to investigate the process of phospholipid biogenesis in sporozoites. Lipidomic analyses demonstrated the occurrence of prototypical phospholipids along with abundant expression of at least two exclusive lipids, phosphatidylthreonine (PtdThr) and inositol phosphorylceramide with a phytosphingosine backbone, in sporozoites. To produce them de novo, the parasite harbors nearly the entire biogenesis network, which is an evolutionary mosaic of eukaryotic-type and prokaryotic-type enzymes. Notably, many have no phylogenetic counterpart or functional equivalent in the mammalian host. Using Toxoplasma gondii as a gene-tractable surrogate to examine Eimeria enzymes, we show a highly compartmentalized network of lipid synthesis spread primarily in the apicoplast, endoplasmic reticulum, mitochondrion, and Golgi complex. Likewise, trans-genera complementation of a Toxoplasma mutant with the PtdThr synthase from Eimeria reveals a convergent role of PtdThr in fostering the lytic cycle of coccidian parasites. Taken together, our work establishes a model of autonomous membrane biogenesis involving significant inter-organelle cooperation and lipid trafficking in sporozoites. Phylogenetic divergence of certain pathways offers attractive drug targets to block the sporulation and subsequent transmission. Not least, our results vindicate the possession of an entire de novo lipid synthesis network in a representative protist adapted to an obligate intracellular parasitic lifestyle. |
| Databáze: | OpenAIRE |
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