Chapter 9 : Antibiotics and the Apicoplast

Abstract:

The discovery of the apicoplast heightened and broadened the therapeutic role of antibiotics, some of which were already useful in malaria chemotherapy and prophylaxis. Although the apicoplast was definitively identified in 1997, it had actually been seen in the early 1960s by those studying malaria parasites under electron microscopes. Researchers hypothesized that the plastid-like DNA had arisen when the ancestor of the malaria parasites took up an algal cell and then incorporated it into its own body. The discovery of streptomycin was the catalyst for the pharmaceutical industry to engage in a race to find new antibiotics. Tetracyclines were produced by the golden-colored Streptomyces aureofaciens and were called aureomycin. Doxycycline had an advantage over some other teracyclines in that it is rapidly removed by the liver and hence does not produce kidney toxicity. Researchers concluded that the antibiotics with distinct mechanisms of action in prokaryotes inhibited the survival of Plasmodium falciparum in vitro by virtue of their action on the mitochondrion. This chapter also discusses the effects of some antibiotics on the apicoplast ribosome. Treatment of malaria patients with antimalarial drug combinations that include azithromycin has shown promise in clinical trials because of the effect of these drugs on the apicoplast.