Polyunsaturated fatty acids promote Plasmodium falciparum gametocytogenesis

The molecular triggers of sexual differentiation into gametocytes by blood stage Plasmodium falciparum, the most malignant human malaria parasites, are subject of much investigation for potential transmission-blocking strategies. The parasites are readily grown in vitro with culture media supplemented by the addition of human serum (10%) or by a commercially available substitute (0.5% AlbuMAX). We found better gametocytemia with serum than AlbuMAX, suggesting suboptimal concentrations of some components in the commercial product; consistent with this hypothesis, substantial concentration differences of multiple fatty acids were detected between serum- and AlbuMAX-supplemented media. Mass spectroscopy analysis distinguished the lipid profiles of gametocyte- and asexual stage-parasite membranes. Delivery of various combinations of unsaturated fatty-acid-containing phospholipids to AlbuMAX-supported gametocyte cultures improved gametocyte production to the levels achieved with human-serum-supplemented media. Maturing gametocytes readily incorporated externally supplied d5-labeled glycerol with fatty acids into unsaturated phospholipids. Phospholipids identified in this work thus may be taken up from extracellular sources or generated internally for important steps of gametocyte development. Further study of polyunsaturated fatty-acid metabolism and phospholipid profiles will improve understanding of gametocyte development and malaria parasite transmission.