Plastid in Human Parasites

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Plastid in Human Parasites SCIENTIFIC CORRESPONDENCE being otherwise homo­ Plastid in human geneous. The 35-kb genome-containing organ­ parasites elle identified here did not escape the attention of early Sm - The discovery in malarial and toxo­ electron microscopists who plasmodial parasites of genes normally - not expecting the pres­ occurring in the photosynthetic organelle ence of a plastid in a proto­ of plants and algae has prompted specula­ zoan parasite like tion that these protozoans might harbour Toxoplasma - ascribed to it a vestigial plastid1• The plastid-like para­ various names, including site genes occur on an extrachromosomal, 'Hohlzylinder' (hollow cylin­ maternally inherited2, 35-kilobase DNA der), 'Golgi adjunct' and circle with an architecture reminiscent of 'grof3e Tilkuole mit kriiftiger that of plastid genomes3•4• Although the Wandung' (large vacuole 35-kb genome is distinct from the 6-7-kb with stout surrounds) ( see linear mitochondrial genome3-6, it is not refs cited in ref. 9). Our pre­ known where in the parasite cells the plas­ liminary experiments with tid-like genome resides. Plasmodium falciparum, the To determine whether a plastid is pre­ causative agent of the most sent, we used high-resolution in situ lethal form of malaria, hybridization7 to localize transcripts of a identify an organelle (not plastid-like 16S ribosomal RNA gene shown) which appears sim­ from Toxoplasma gondii8, the causative ilar to the T. gondii plastid. agent of toxoplasmosis. Transcripts accu­ The number of surrounding mulate in a small, ovoid organelle located membranes in the P. anterior to the nucleus in the mid-region falciparum plastid, and its of the cell (a, b in the figure). We observe relationship to the previous­ only one of these organelles per cell (a--c ), ly described spherical body except during division ( endodyogeny), of Plasmodium (see ref. 9), when an organelle is associated with each are unknown. Our in situ forming daughter cell (not shown). At the hybridization data thus onset of endodyogeny, the organelle identify a third, hither­ assumes a cylindrical shape (not shown) to putative, genetic com­ and eventually acquires a constriction, partment (a plastid) creating a dumbbell shape (e, fin the fig­ in these parasite cells. a, Localization of transcript s from a plastid-l ike 16S rRNA gene8 in tachyzoite (longitudinal section) of Toxoplasma ure) which presumably divides into two Because the plastid genome gondii RH by high-resolut ion in situ hybridization. Colloidal daughter organelles. The organelle is dis­ encodes components of gold markers show transcripts accumulated in an ovoid com­ tinct from the tubulocristate mitochondria ribosomes and the transla­ partment (arrow). Nu, nucleus; Rh, rhoptries; and M i, mito­ (c). At least two membranes (some pro­ tion process4·JO, and we chondria. b, Standard elect ron micrograph ( embedment files possibly indicate a third membrane) observe ribosome-like courtesy of D. Lindsay, Auburn University) similar t o a, show­ surround the organelle (b-f). Certain particles in it, the ing t he plastid (arrow). c, Mitochondria (Mi) with tubular images (e in the figure) reveal a layer of plastid compartment proba­ cristae are not labelled. d, Close view of plastid showing at endoplasmic reticulum (sometimes bly contains machinery least two surrounding membranes, homogeneous cont ents completely) enveloping the organelle, to express its information and ribosome-like particles (about 18 nm diameter). e, Dumb­ bell-shaped (possibly dividing), double-membrane-bound creating a misleading impression of multi­ content. (black arrows) Toxoplasma plastid. Endoplasmic ret iculum ple ( typically four or five) surrounding Toxoplasma and Plas­ appressed to the plastid (white arrow) creates impression of membranes. modium belong to phylum extra surrounding membranes. f, Standard electron micro­ Particles of 18 nm diameter (approxi­ Apicomplexa, which is graph showing dumbbell-shaped Toxoplasma plastid with two mately the size of bacterium-like 70S ribo­ closely related to dino­ surrounding membranes (black arrows) and ribosome-like par­ somes) are the only discernible structures flagellate algae ( refs in ref. ticles (about 18 nm diamet er) within. Scale bars, 0 .2 µm. within the organelle (d, f), the contents 3), so the parasite plastid could be a non-photosynthetic complement molecular-genetic approach­ derivative of the dinoflagellate plastid es already under way4•10• 1. Wilson, R. J.M. Nature 366, 638 (1993). 2. Creasey, A. et al. Malec. biochem. Parasit. 65, 95--98 (but see ref. 5). Unfortunately, no genes Geoffrey I. McFadden (1994). have yet been characterized from dino­ Plant Cell Biology Research Centre, 3. Palmer, J. D. Curr. Biol. 2 , 318-320 (1992). flagellate plastids, so molecular compari­ School of Botany, 4 . Preiser, P., Williamson, D. H. & Wilson, R. J. M. Nucleic Acids Res. 23, 4329-4336 (1995). son of dinoflagellate and apicomplexan University of Melbourne, 5 . Wilson, R. J. M., Williamson, D. H. & Preiser, P. Infect . plastids must wait. Whatever its origin, Victoria 3052, Australia Ag. Dis. 3, 29- 37 (1994). 6 . Feagin, J.E. A. Rev. Microbial. 48, 81- 104 (1994). the presence of a plastid in apicomplexan Michael E. Reith 7. McFadden, G. I. in Electron Microscopy of Plant Cells parasites probably explains their sensitiv­ Janet Munholland (eds Hall, J. L. & Hawes, C. R.) 219--255 (Cambridge Univ. Press, 1991). ity to certain herbicides (ref. 11 and refs Institute for Marine Biosciences, 8. Egea, N. & Lang-Unnasch, N. J. eukaryot. Microbial. 42, therein) and drugs inhibiting plastid National Research Council, 679--684 (1995). metabolism 12•13• The plastid is thus a wel­ Halifax B3H 3Z1 , 9 . Siddall , M. E. Parasit. Today 8, 90--91 (1992). 10. Beckers, C. J.M. et al. J. clin. Invest. 95, 367- 376 come new, parasite-specific target for Nova Scotia, Canada (1995). therapeutic agents. The role of the plastid Naomi Lang-Unnasch 11. Hackstein, J. H. P. et al. Parasit. Res. 81, 207- 216 (1995). in obligate intracellular parasites is com­ Division of Geographic Medicine, 12. Strath, M. et al. Trans R. Soc. Trap. med. Hyg. 87, pletely unknown, but our identification Department of Medicine, 211- 216 ( 1993). 13. Pukrittayakamee, S. et al. Antimicrob. Ag . Chemother. of the organelle is a first step towards University of Alabama at Birmingham, 3842, 511-514 (1994). isolation for biochemical analysis to Birmingham, Alabama 35294-2170, USA 482 NA.TURE · VOL 381 · 6 JUNE 1996 .
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