A plastid organelle as a drug target in apicomplexan parasites
- 1 November 1997
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 390 (6658), 407-409
- https://doi.org/10.1038/37132
Abstract
Parasites of the phylum Apicomplexa include many important human and veterinary pathogens such as Plasmodium (malaria), Toxoplasma (a leading opportunistic infection associated with AIDS and congenital neurological birth defects), and Eimeria (an economically significant disease of poultry and cattle)1,2,3,4. Recent studies have identified an unusual organelle in these parasites5,6,7: a plastid that appears to have been acquired by secondary endosymbiosis of a green alga7. Here we show that replication of the apicomplexan plastid (apicoplast) genome in Toxoplasma gondii tachyzoites can be specifically inhibited using ciprofloxacin, and that this inhibition blocks parasite replication. Moreover, parasite death occurs with peculiar kinetics that are identical to those observed after exposure to clindamycin and macrolide antibiotics8,9, which have been proposed to target protein synthesis in the apicoplast9,10. Conversely, clindamycin (and functionally related compounds) immediately inhibits plastid replication upon drug application—the earliest effect so far described for these antibiotics. Our results directly link apicoplast function with parasite survival, validating this intriguing organelle as an effective target for parasiticidal drug design.Keywords
This publication has 25 references indexed in Scilit:
- A Plastid of Probable Green Algal Origin in Apicomplexan ParasitesScience, 1997
- Complete Gene Map of the Plastid-like DNA of the Malaria ParasitePlasmodium falciparumJournal of Molecular Biology, 1996
- Plastid in human parasitesNature, 1996
- Chemotherapy of human and animal coccidioses: state and perspectivesZeitschrift Fur Parasitenkunde-Parasitology Research, 1996
- In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondiiAntimicrobial Agents and Chemotherapy, 1995
- Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics.JCI Insight, 1995
- Recent Advances in the Management of AIDS-related Opportunistic InfectionsAnnals of Internal Medicine, 1994
- Toxoplasmic Encephalitis in Patients with the Acquired Immunodeficiency SyndromeNew England Journal of Medicine, 1993
- Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutantAntimicrobial Agents and Chemotherapy, 1992
- Progress in Taxonomy of the Apicomplexan ProtozoaThe Journal of Protozoology, 1988