Lactic acid supplementation increases quantity and quality of gametocytes in Plasmodium falciparum culture.

Malaria infection by Plasmodium falciparum continues to afflict millions of people worldwide, with transmission dependent upon mosquito ingestion of the parasite gametocyte stage. These sexually committed stages develop from the asexual stages, yet the factors behind this transition are not completely understood. Here we find that lactic acid increases gametocyte quantity and quality in P. falciparum culture. Low passage NF54 parasites with varied time exposures of 8.2 mM lactic acid were monitored using blood film gametocyte counts and RNA analysis throughout two weeks of gametocyte development in vitro for a total of 5 biological cohorts. We found that daily continuous media exchange and 8.2 mM lactic acid supplementation increased gametocytemia by approximately 2- to 6-fold relative to controls after 5 days. In membrane feeding mosquito infection experiments, we found that gametocytes continuously exposed to 8.2 mM lactic acid supplementations were more infectious to Anopheles stephensi mosquitoes, essentially doubling prevalence of infected midguts and oocyst density. Supplementation on days 9-16 did not increase quantity of gametocytes, but did increase quality as measured by oocyst density by 2.4-fold. Lactic acid did not impact asexual growth as measured by blood film and luciferase quantification, as well as radioactive hypoxanthine incorporation assays. These data indicate a novel role for lactic acid in sexual development of the parasite.