Lipid trafficking between high density lipoproteins and Babesia divergens‐infected human erythrocytes

Abstract

A two-fold increase in the amount of phospholipids was observed in Babesia divergens infected human red blood cells. In vitro incubation with [32P]-phosphorus and [3H]-glycerol demonstrated that B divergens has the ability to synthesize the phospholipid backbone. On the other hand, the low incorporation of [14C]acetate indicated the absence of a de novo fatty acid synthesis and suggested the necessity of an exogenous lipid source for the parasite. Several intra-erythrocytic growth cycles of B divergens could be achieved in vitro, using a serum-free medium supplemented only with fractions of human high density lipoproteins (HDL). At an HDL concentration of 0.5 mg/ml (protein concentration) and with a 1% starting parasitaemia, parasite growth was similar to that observed under standard culture conditions with 10% human serum, at least for the first 24 h, a time equivalent to three parasite erythrocytic life-cycles. Lipid transfer from HDL to the intra-erythrocytic parasites was demonstrated by uptake and exchange of fluorescent NBD-phosphatidylcholine (NBD-PC) loaded HDL at different temperatures. Kinetic experiments with [3H]-oleyl-PC-loaded HDL demonstrated a unidirectional transfer of lipids from radiolabelled HDL to the parasite; partial conversion of PC to phosphatidylethanolamine (PE) was also observed. In the semi-defined medium, the HDL fraction appeared to be the major source of lipids for the growth of B divergens in human erythrocytes.

Babesia divergens , a Bovine Blood Parasite of Veterinary and Zoonotic Importance

“…Subsequently the whole cell divides into two haploid merozoites, which escape by lysing the old host cell and invading new ones. One cycle of asexual reproduction takes about 8 h in vitro (181). The vast majority of merozoites continue to multiply asexually, while a small proportion turn into nondividing spherical gamonts, which remain inside erythrocytes until they are taken up by ticks during feeding (128).…”

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit in vitro development of Plasmodium falciparum and Babesia divergens in human erythrocytes

“…A similar phospholipid transfer was observed in B. divergensinfected erythrocytes (RBC), but no ducts or vesicles were observed (21). High-density lipoproteins support the in vitro growth of B. divergens and P. falciparum in the absence of other major serum components and appeared to be a lipid source for the parasites (6,7,21 by P. falciparum-infected RBC, we have shown evidence for an isoprenoid metabolisnm until, at least, the farnesyl PPi step (16).…”

“…A similar phospholipid transfer was observed in B. divergensinfected erythrocytes (RBC), but no ducts or vesicles were observed (21). High-density lipoproteins support the in vitro growth of B. divergens and P. falciparum in the absence of other major serum components and appeared to be a lipid source for the parasites (6,7,21 by P. falciparum-infected RBC, we have shown evidence for an isoprenoid metabolisnm until, at least, the farnesyl PPi step (16).This pathway, with numerous end products, is essential for various cellular functions such as mitochondrial electron transport, tRNA synthesis, control of cell growth, protein glycosylation, and intracellular targeting (4). In both prokaryotic and eukaryotic cells, the isoprenoid pathway is highly regulated through feedback regulations at the level of two sequential enzymes involved in the synthesis of mevalonate: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMGCoA reductase (4).…”

“…The (8,21,22) and depend on their import from the host's plasma. With the use of a serum-free medium, we have recently found a unidirectional transfer of phospholipids from human high-density lipoproteins to the intraerythrocytic P. falciparum by ducts and vesicles moving from the erythrocyte to the parasitophorous vacuole membranes (6).…”

Undetectable HDL Cholesterol in a Patient with Flu-Like Illness

“…The biology of the parasite may also be relevant. Species of both Babesia and Plasmodium have been shown to lack the ability to synthesize essential lipids and to transfer these from host lipoproteins, particularly HDL (8 ). For Plasmodium (malaria) infection, an association with decreased HDL-C has been observed, but it has been inconsistent and generally not to extremely low concentrations (9 ).…”