Apicomplexans

Apicomplexan parasites cause life threatening diseases like malaria, cryptosporid-iosis, toxoplasmosis, coccidiosis. Suberic acid bisdimethylamide which also inhibits HDA selechvely arrests tumor cells as opposed to normal mammalian cells, has an in vivo cytostatic effect against the acute murine malaria Plasmodium berghei (Andrews et al, 2000). 

Neospora caninum is an apicomplexan parasite that causes abortion in cattle. Depudecin is an inhibitor of these parasites without exerting any cytotoxicity on the host cells. This inhibitor targets the protozoal histone deacetylases (Kwon et al, 2003). 

Apicidin (Fig. 10) was first isolated from fimgus Fusarium pallidoroseum ATCC 74289, MF6040, from Acacia sp. (collected from Santa Rosa National Park Costa Rica) as an antiprotozoal agent. It was found that apicidin was active against wide range of protozoans specially Apicomplexan parasites. The underlying mechanism for this cidal activity was found out to be HDAC inhibition of protozoas. It was also observed that they were very potent HDAC inhibitors when compared to similar cyclopeptide inhibitors known at that time (Table 5). 

Abe Y et al. (2000) Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100 551-560 Abrahamsen MS et al. (2004) Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304 441-445... 

LaGier MJ, Tachezy J, Stejskal F, Kutisova K, Keithly JS (2003) Mitochondrial-type iron-sulfur cluster biosynthesis genes (IscS and IscU) in the apicomplexan Cryptosporidium parvum. Microbiology 149 3519-3530... 

Rotte C, Stejskal F, Zhu G, Keithly JS, Martin W (2001) Pyruvate NADP+ oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan Cryptosporidium parvum a biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists. Mol Biol Evol 18 710-720 Schnarrenberger C, Martin W (2002) Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer. Eur J Biochem 269 868-883... 

C. parvum is a protist related to the apicomplexans P. falciparum and Toxoplasma. P. falciparum and T gondii possess the apicoplast organelle, a remnant plastid acquired by secondary symbiosis. It has been shown that the I gondii apicoplast is segregated into daughter cells by microtubules of mitotic spindle poles (Striepen et al. 2000). As the apicoplast is in contact with the mitochondrion, it has been hypothesized that mitochondrial inheritance... 

C. parvum is the apicomplexan which lacks an apicoplast, direct contact between the mitosomes and mitotic spindle might be expected. There is still no information available on the movement and segregation of the mitosomes of... 

The machinery mediating this process was shown to be of an ISC type. Phylogenetic analyses indicate that the mitochondrial ISC machinery was inherited from the proteobacterial endosymbiont, which is consistent with the proposed origin of mitochondria (Tachezy et al. 2001). Components of the SUF system were found in plastids and in the apicoplast of apicomplexan such as P. falciparum (Wilson et al. 2003). The SUF machinery was most likely inherited from cyanobacteria, the ancestors of plastids (Tachezy et al. 2001). Entamoebids and related protists are the only eukaryotes which acquired components of the NIF system ( et al. 2004 van der Giezen et al. 

Similarly to microsporidia, our knowledge of the FeS cluster assembly in the amitochondrial apicomplexan C. parvum is based mainly on the identification of genes coding for components of the FeS cluster assembly machinery in the parasite s genome and reconstruction of the hypothetical pathway in the mitosomes (Table 1). The presence of cryptosporidian IscS and IscU was... 

Cryptosporidium parvum belongs to the diverse group of intracellular apicomplexans that includes species of human (Babesia microti, Plasmodium falciparum, Toxoplasma gondii) and veterinary (Eimeria tenella, Neospora caninum) importance (Ellis et al. 1998 Fayer 1997 Thompson et al. 2005). While a single mitochondrion is present in most Apicomplexa (McFadden... 

Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V (2004) Complete genome sequence of the apicomplexan Cryptosporidium parvum. Science 304 441-445 Aji T, Flanigan T, Marshall R, Kaetzel C, Aikawa M (1991) Ultrastructural study of asexual development of Cryptosporidium parvum in a human intestinal cell line. J Protozool 38 82S... 

Cai X, Herschap D, Zhu G (2005) Functional characterization of an evolutionarily distinct phosphopantetheinyl transferase in the apicomplexan Cryptosporidium parvum. Eukaryot Cell 4 1211-1220... 

Morrissette NS, Sibley LD (2002) Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev 66 21-38... 

Suzuki T, Hashimoto T, Yabu Y, Kido Y, Sakamoto K, Nihei C, Hato M, Suzuki S, Amano Y, Nagai K, Hosokawa T, Minagawa N, Ohta N, Kita (2004) Direct evidence for cyanide-insensitive quinol oxidase (alternative oxidase) in the apicomplexan parasite Cryptosporidium parvum phylogenetic and therapeutic implications. Biochem Biophys Res Commun 313 1044-1052... 

Kim, K. and Weiss, L.M. (2004) Toxoplasma gondii the model apicomplexan. International journal for Parasitology 34, 423-432. 

Jean, L., Long, M., Young, J., Pery, P. and Tomley, F. (2001) Aspartyl proteinase genes from apicomplexan parasites evidence for evolution of the gene structure. Trends in Parasitology 17, 491 t98. 

Further modifications using the same strain of ODC S. cerevisiae reconstituted a bacterial/plant polyamine synthesis pathway in yeast [41], The ODC strain was transformed with plasmids encoding arginine decarboxylase and ag-matine ureohydrolase, which conferred polyamine-independent growth on the recombinant microbe. A similar construction could be used to screen for inhibitors of the homologous enzymes from Apicomplexan protozoa, which synthesize poly amines through this pathway [42]. 

F Dzierszinski, O Popescu, C Toursel, C Slomianny, B Yahiaoui, S Tomavo. The protozoan parasite Toxoplasma gondii expresses two functional plant-like glycolytic enzymes. Implications for evolutionary origin of apicomplexans. J Biol Chem 274 ... 

CH Sibley, VH Brophy, S Cheesman, KL Hamilton, EG Hankins, JM Wooden, B Kilbey. Yeast as a model system to study drugs effective against apicomplexan proteins. Methods 13 190-207, 1997. 

M Soete, C Hettman, D Soldati. The importance of reverse genetics in determining gene function in apicomplexan parasites. Parasitology 118 S53-S61, 1999. 

Fichera ME, Roos DS (1997) A plastic organelle as a drug target in apicomplexan parasites. Nature 390 407-109... 

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