Influence of 9-beta-D-arabinofuranosyladenine on total protein synthesis and on differential gene expression of unique proteins in the rodent malarial parasite Plasmodium berghei.

The antibiotic 9-beta-D-arabinofuranosyladenine is a drug with a broad spectrum of activity against animal viruses, with little or no effect on mammalian cells, when administered in vivo or in vitro. Here we report that the antibiotic markedly inhibited the incorporation of [35S]methionine into malarial protein. Inhibition was apparent when the parasites were either exposed to the drug in vivo during the course of infection or incubated with the drug in vitro. Moreover, the antibiotic induced pronounced changes in the spectrum of proteins synthesized. Some proteins that are prominently apparent in the control disappear from the drug-treated parasites; others specific for drug-treated parasites appear, indicating changes in the commitment for gene expression as manifested by the appearance of the final protein product. Proteins synthesized were analyzed by two-dimensional polyacrylamide gels; the first dimension used isoelectric focusing in cylinder gels and the second dimension used electrophoresis in a lithium dodecyl sulfate slab gel. Proteins were visualized by radioautography.