Lipid Exchange between Borrelia burgdorferi and Host Cells

Abstract

Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or ³H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

Author Summary

Lyme disease, the most prevalent arthropod-borne disease in North America, is caused by the spirochete Borrelia burgdorferi. Cholesterol is a significant component of the B. burgdorferi membrane lipids, and is processed to make cholesterol-glycolipids. Our interest in the presence of cholesterol in B. burgdorferi recently led to the identification and characterization of eukaryotic-like lipid rafts in the spirochete. The presence of free cholesterol and cholesterol-glycolipids in B. burgdorferi creates an opportunity for lipid-lipid interactions with constituents of the lipid rafts in eukaryotic cells. We present evidence that there is a two-way exchange of lipids between B. burgdorferi and epithelial cells. Spirochetes are unable to synthesize cholesterol, but can acquire it from the plasma membrane of epithelial cells. In addition, free cholesterol and cholesterol-glycolipids from B. burgdorferi are transferred to epithelial cells through direct contact and through outer membrane vesicles. The exchange of cholesterol between spirochete and host could be an important aspect of the pathogenesis of Lyme disease.