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: Apicomplexan parasites, Toxoplasma, Plasmodium, apicoplast, transcription, translation, DNA replication, delayed death phenomenon, toposiomerase, ciprofloxacin
Current Drug Targets
Title: Targeting the Transcriptional and Translational Machinery of the Endosymbiotic Organelle in Apicomplexans
Volume: 9 Issue: 11
Author(s): Tobias Fleige and Dominique Soldati-Favre
Affiliation:
Keywords: Apicomplexan parasites, Toxoplasma, Plasmodium, apicoplast, transcription, translation, DNA replication, delayed death phenomenon, toposiomerase, ciprofloxacin
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.
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Cite this article as:
Fleige Tobias and Soldati-Favre Dominique, Targeting the Transcriptional and Translational Machinery of the Endosymbiotic Organelle in Apicomplexans, Current Drug Targets 2008; 9 (11) . https://dx.doi.org/10.2174/138945008786786073
DOI https://dx.doi.org/10.2174/138945008786786073 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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