The researchers of College of Medicine (Pennsylvania) and Iowa University have published on ‘Dramatic Consequences of Reducing Erythrocyte Membrane Cholesterol on Plasmodium falciparum’ achieved by treatment using methyl BCD.
Malaria remains a major challenge in much of the world. Symptoms of malaria are caused by the growth of parasites belonging to Plasmodium spp. inside the red blood cells (RBCs), leading to their destruction. The parasite depends upon its host for much of its nutritional needs. Cholesterol is a major lipid in the RBC plasma membrane, which is the only source of this lipid for malaria parasites. The authors have previously shown that certain new antimalarial compounds disrupt cholesterol homeostasis in P. falciparum. Here, they use live time-lapse video microscopy to show dramatic expulsion of the parasite from the host RBC when the cholesterol content of the RBC is reduced. By using time-lapse video microscopy of fluorescently tagged parasites, it is shown that MβCD treatment for just 30 min causes dramatic expulsion of the trophozoite-stage parasites. This forceful expulsion occurs within 10 s. Remarkably, this expulsion is inhibited by the antimalarials that disrupt lipid homeostasis. Theauhors also show stereospecificity of cholesterol in supporting parasite growth inside RBC. Overall, these results point to a critical role of cholesterol in the physiology of malaria parasites.
Avantika I Ahiya, Suyash Bhatnagar, Joanne M Morrisey, Josh R Beck, Akhil B Vaidya (2022) Dramatic Consequences of Reducing Erythrocyte Membrane Cholesterol on Plasmodium falciparum. Microbiol Spectr 10(1):e0015822. doi: 10.1128/spectrum.00158-22.