Echinococcus granulosus Antigen B acquires cholesterol from membranes and lipoproteins in vitro
The larva stage (hydatid) of Echinococcus granulosus establishes a chronic infection (cystic echinococcosis) primarily in the host’s liver and lungs. Its adaptation to an environment rich in nutrients has shaped the parasite’s metabolism, resulting in the loss of de novo fatty acid and cholesterol s...
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| Format: | article |
| Jezik: | angleščina |
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2025
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| Online dostop: | https://hdl.handle.net/20.500.12008/53318 |
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| Izvleček: | The larva stage (hydatid) of Echinococcus granulosus establishes a chronic infection (cystic echinococcosis) primarily in the host’s liver and lungs. Its adaptation to an environment rich in nutrients has shaped the parasite’s metabolism, resulting in the loss of de novo fatty acid and cholesterol synthesis pathways. Therefore, these essential lipids must be obtained from the host. Antigen B (EgAgB), the main larval lipoprotein, is composed of several protein subunits (EgAgB8/1-5) and diverse lipid classes, including cholesterol and fatty acids. As a member of the cestode-specific hydrophobic ligand-binding protein family, EgAgB is believed to participate in the acquisition and transport of host lipids to the parasite, although the exact mechanisms remain unclear. Our group previously demonstrated that delipidated EgAgB apolipoproteins can bind and transfer fatty acids to artificial phospholipid membranes. More recently, we found that EgAgB promotes the efflux of radiolabelled cholesterol from THP-1-derived macrophages and hepatocytes mainly through a receptor-independent mechanism. Herein, we focused on the cholesterol uptake activity of EgAgB, investigating whether it involves a passive diffusion mechanism from the cell membrane. Moreover, we explored the potential role of plasma lipoproteins as an additional source of host cholesterol, given their described ability to exchange lipids. EgAgB's capacity to acquire cholesterol via passive diffusion from the membrane was analysed using liposomes as a lipid bilayer model. POPC (1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine) liposomes were loaded with fluorescent cholesterol and incubated overnight with recombinant EgAgB8/1 (rEgAgB). After affinity purification of rEgAgB, eluted fractions were analysed by spectroscopy for liposome-scattering signal and fluorescence spectrum. The detection of fluorescent cholesterol, but not of liposomes, in the eluted rEgAgB supported EgAgB’s ability to extract cholesterol directly from lipid bilayers, without a receptor-driven mechanism. We conducted similar experiments to assess whether hHDL could serve as another cholesterol source, loading it with fluorescent cholesterol. rEgAgB acquired cholesterol from hHDL and maintained a strong binding, as the dissociation of the two lipoproteins required low pH conditions. Finally, studies for analysing the ability of rEgAgB to deliver cholesterol to liposomes or lipoproteins are in progress. Altogether, these findings support that EgAgB can interact with both cell membranes and hHDL to acquire cholesterol—an essential lipid for the hydatid—highlighting its potential role in lipid metabolism and in E. granulosus adaptation to its host. |
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