Apicoplast translation, transcription and genome replication: targets for antimalarial antibiotics

Trends Parasitol. 2008 Jun;24(6):279-84. doi: 10.1016/j.pt.2008.03.007. Epub 2008 Apr 29.

Abstract

Several antibiotics possess antimalarial properties, although the mechanisms by which they kill malaria parasites have been poorly understood. Recent data suggest that the target for multiple antimalarial antibiotics is the apicoplast, a chloroplast-like organelle of uncertain function. Translation inhibitors (such as tetracyclines, clindamycin and macrolides) and gyrase inhibitors (such as ciprofloxacin) cause modest antimalarial effects initially but are much more potent against the progeny of treated parasites. These progeny inherit nonfunctional apicoplasts, suggesting that blocking production of apicoplast proteins causes the 'delayed-death effect'. Interestingly, the antibiotics thiostrepton and rifampin are fast acting and might target additional processes outside the apicoplast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimalarials / pharmacology*
  • Apicomplexa / drug effects
  • Apicomplexa / metabolism
  • DNA Replication / drug effects
  • DNA, Protozoan / biosynthesis
  • DNA, Protozoan / genetics
  • Gene Expression / drug effects
  • Humans
  • Organelles / drug effects*
  • Organelles / genetics
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / genetics
  • Plasmodium falciparum* / growth & development
  • Protozoan Proteins / metabolism
  • Transcription, Genetic*

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • DNA, Protozoan
  • Protozoan Proteins