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Targeting the transcriptional and translational machinery of the endosymbiotic organelle in apicomplexans

Published in Current drug targets. 2008, vol. 9, no. 11, p. 948-56
Abstract Apicomplexans are obligate intracellular parasites causing devastating disease in both humans and livestock. Nearly all apicomplexans, with the exception of Cryptosporidium, contain two endosymbiontic organelles carrying their own DNA; the mitochondrion and the plastid-like organelle called the apicoplast. The apicoplast is an attractive drug target as it harbors not only metabolic pathways not found in the host cell, but it is also dependent on its ancient transcriptional and translational machinery. These parasites rely on the plastid, and inhibition of its function or loss of this organelle leads to immediate or delayed death. Replication of plastidic DNA shows differences between the members of this phylum. In Plasmodium parasites, two forms of replication are observed--unidirectional single-stranded replication and a rolling circle mechanism--whereas in Toxoplasma gondii only the rolling circle is found. Targeting enzymes involved in DNA-replication leads to a delayed death of the parasite. Most of the genes in the apicoplast genome encode elements of their own transcriptional and translational machinery, and they are highly similar to those found in bacteria. Several anti-bacterials which target this machinery are also active against apicomplexan parasites and inhibition leads mostly to the delayed death phenomenon.
Keywords AnimalsAntiprotozoal Agents/pharmacologyApicomplexa/drug effects/genetics/metabolismDNA Replication/drug effectsGenome, Plastid/geneticsModels, BiologicalOrganelles/drug effects/genetics/metabolismPlastids/drug effects/genetics/metabolismProtein Biosynthesis/drug effectsTranscription, Genetic/drug effects
PMID: 18991607
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Research group Biologie d'un parasite intracellulaire obligatoire (773)
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FLEIGE, Tobias, SOLDATI-FAVRE, Dominique. Targeting the transcriptional and translational machinery of the endosymbiotic organelle in apicomplexans. In: Current drug targets, 2008, vol. 9, n° 11, p. 948-56. doi: 10.2174/138945008786786073 https://archive-ouverte.unige.ch/unige:2233

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Deposited on : 2009-07-17

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