The accumulation of lactic acid and its influence on the growth of Plasmodium falciparum in synchronized cultures.
Synchronization of Plasmodium falciparum cultured in vitro results in a one-step growth pattern that allows the study of stage-specific metabolic activities of the parasites. Lactic acid (LA) was selected as a metabolic marker, and the concentration of this end product found in spent media was correlated with the different erythrocytic stages of the parasites. When the medium was changed at 12 h intervals, cultures containing predominantly trophozoites produced 3.66 +/- 0.55 mumol LA per 12 h per 10(7) parasitized cells (n = 26), an amount of LA that is about 8 to 20 times higher than that found in corresponding cultures containing predominantly ring forms. Depending on the stage of development, parasitized red blood cells produced between 5 and 100 times more LA than uninfected erythrocytes (3.72 +/- 0.62 mumol LA per 12 hours per 10(9) red blood cells) (n = 41) when cultured under identical conditions. The intraerythrocytic development of the parasites was not impaired by exposure to extracellular concentrations of LA up to 12 mM over a 12 h period. The growth resulting in such cultures was described as uninhibited and was characterized by a multiplication index of 10 or higher. Above the threshold of 12 mM of LA, progressive inhibition of parasite development occurred. The stage-specific LA production reported can be used to predict the amount of LA that will have accumulated at the end of a subsequent 12 h incubation period during synchronized in vitro growth of Plasmodium falciparum. Using these values, it is possible to establish an optimal medium exchange schedule, thereby assuring uninhibited growth and a correspondingly high parasite yield.
D000818:Animals; D003470:Culture Media; D004912:Erythrocytes / Q000469:parasitology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000096:biosynthesis* / Q000494:pharmacology; D019344:Lactic Acid; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D007773:Lactates; D019344:Lactic Acid; D005947:Glucose