Accumulations and Energy Recycling Pathway in P. Falciparum Gametocyte-Infected Human Erythrocytes

Abstract

Quick emergence of drug resistant phenotypes of Plasmodium falciparum against new anti-malarial drugs have been a serious problem in the clinical field fighting malaria. Since no effective malaria vaccine is available, transmission-blocking targeting gametocyte and gemtocytegenesis may be an excellent alternative approach. Gamtocyte parasite exhibits lower sensitivity against currently available anti-malarial drugs and characteristic biology that is quite different from that in asexual intraerythrocytic stages. However, our understanding gametocyte biology is still premature for leading an effective transmission-blocking drug to stop parasites moving to mosquito stages. In this study, we focused on lipid metabolism, particularly lipid accumulation and recycling of the lipid storage. With fluorescence microscopy study, gametocyte showed marked increases in the total lipid amount as well as lipid droplets in parasite cytoplasm while no significant increase in cholesterol, demonstrating a unique lipid environment is developed inside parasite. However, hyperspectral imaging showed most of hemoglobin molecules were consumed during gemetocytegenesis indicating its correlation with lipid productions and accumulations. Gametocytes are taken by mosquito and continue active stages where high amount of energy must be supplied. Therefore, we hypothesized that accumulated lipids will be recycled through gluconeogenesis consuming triacylglycerides (TAG) as a supplemental energy source to obtain dihydroacetonephosphate that is involved in the normal glycolysis. We used high-sensitivity LC/MS and quantified relative amount ratio of TAG and glycerol, an intermediate product in gluconeogenesis, to compare between asexual and gametocyte stages.