A plastid organelle as a drug target in apicomplexan parasites

Maria E. Fichera and David S. Roos ()
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Maria E. Fichera: University of Pennsylvania
David S. Roos: University of Pennsylvania

Nature, 1997, vol. 390, issue 6658, 407-409

Abstract: 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.

Date: 1997
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DOI: 10.1038/37132

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