Stage- and time-dependent effects of crisis form factor on Plasmodium falciparum in vitro

To determine the stage- and time-dependent effects of crisis form factor (CFF) on Plasmodium falciparum metabolism in vitro, the parasite erythrocytic cycle was divided into sequential 8 hr time intervals, and highly synchronous parasites were exposed to CFF for various lengths of time. Hypoxanthine and phenylalanine incorporation into parasite nucleic acids and proteins, respectively, and glucose consumption by the parasites were compared in cultures grown in CFF-containing or nonimmune sera. The most profound derangement of metabolism occurred in parasites 0-8 hr post-invasion. Inhibition correspondingly decreased in tests started with progressively older parasites. Cultivation in CFF serum for 8 hr caused maximal inhibition of purine and amino acid incorporation; longer periods of exposure did not increase inhibition. In contrast, CFF's effect on glucose consumption varied inversely to the duration of exposure to CFF. As the parasites matured in the presence of CFF, inhibition of the rate of glucose utilization decreased, with little or no reduction in consumption observed as parasites entered schizogony. Of the 3 metabolic parameters studied, hypoxanthine was the most sensitive indicator of metabolic inhibition throughout the cycle.