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Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum

Ramya, TNC and Mishra, Satyendra and Karmodiya, Krishanpal and Surolia, Namita and Surolia, Avadhesha (2007) Inhibitors of Nonhousekeeping Functions of the Apicoplast Defy Delayed Death in Plasmodium falciparum. In: Antimicrobial Agents and Chemotherapy, 51 (1). pp. 307-316.

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Targeting of apicoplast replication and protein synthesis in the apicomplexan Toxoplasma gondii has conventionally been associated with the typical "delayed death" phenotype, characterized by the death of parasites only in the generation following drug intervention. We demonstrate that antibiotics like clindamycin, chloramphenicol, and tetracycline, inhibitors of prokaryotic protein synthesis, invoke the delayed death phenotype in Plasmodium falciparum, too, as evident from a specific reduction of apicoplast genome copy number. Interestingly, however, molecules like triclosan, cerulenin, fops, and NAS-91, inhibitors of the recently discovered fatty acid synthesis pathway, and succinyl acetone, an inhibitor of heme biosynthesis that operates in the apicoplast of the parasite, display rapid and striking parasiticidal effects. Our results draw a clear distinction between apicoplast functions per se and the apicoplast as the site of metabolic pathways, which are required for parasite survival, and thus subserve the development of novel antimalarial therapy.

Item Type: Journal Article
Publication: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Additional Information: Copyright of this article belongs to American Society for Microbiology.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 08 Mar 2007
Last Modified: 27 Aug 2008 12:35
URI: http://eprints.iisc.ac.in/id/eprint/9660

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