Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes

The asexual development of Plasmodium within the mature mammalian erythrocyte is associated with intense membrane biogenesis, notably to ensure the increase in the size of the parasite and of the parasitophorous vacuolar membranes PVM. A considerable increase in the content of most lipids except cholesterol [namely, phospholipids PL, neutral lipids, and fatty acids FA] occurs. The PL composition and the constitutive FAs of the parasite differ markedly from the original host cell membrane. Particularly notable is the absence of cholesterol and sphingomyelin SM from the parasite membranes. How can the parasite obtain such a quantity of new lipid molecules in a host cell totally devoid of any lipid biosynthetic activity? Like the normal erythrocyte, the infected cell is unable to synthesize cholesterol or FAs. In contrast, it exhibits an intense biosynthesis of neutral lipids and a bewildering variety of PL biosyntheses. Phosphatidylcholine PC is synthesized by a de novo pathway, and also by methylation of phosphatidylethanolamine PE, which itself originates from de novo biosynthesis or from decarboxylation of phosphatidylserine PS. Hence, interference with this intense and specific PL metabolism could provide the basis for a new malaria chemotherapy. Indeed, compounds that interfere with the entry of the plasmatic precursors (FAs or polar heads) or with their metabolism are lethal to the parasite. Lastly, we focus on the structural modifications of the host cell membrane with respect to lipids, including increased fluidity and enhanced transbilayer mobility of PLs. Possible modifications in the asymmetric distribution of PLs in the host cell membrane are discussed in light of the various methods used and their limits. The capacity of infected cells to take up and metabolize large quantities of exogenous vesicles of PLs accounts for the intense dynamics of lipids in the infected erythrocytes.