Functional analysis of a lipid galactosyltransferase synthesizing the major envelope lipid in the Lyme disease spirochete<i>Borrelia burgdorferi</i>

Östberg, Yngve; Berg, Stefan; Comstedt, Pär; Wieslander, Åke; Bergström, Sven

doi:10.1111/j.1574-6968.2007.00728.x

Cited by 28 publications

(29 citation statements)

References 37 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The glycolipids of B. burgdorferi are mono-α-galactosyl-diacylglycerol (MGalD), which does not contain cholesterol; cholesteryl-β-D-galacto-pyranoside (CGal); and cholesteryl 6-O-acyl-β-D-galactopyranoside, or cholesteryl 6-O-palmitoyl-β-D-galactopyranoside (ACGal/Bb-GL-1), which contain cholesterol [3], [11]–[14]. The cholesterol-glycolipids constitute a significant portion, 45% [11], of the total lipid content [3], [5], [12], [13], [15]–[18]. B. burgdorferi does not have the biosynthetic ability to synthesize cholesterol or any long-chain-saturated and unsaturated fatty acids that are required for growth [6].…”

Section: Introductionmentioning

confidence: 99%

Lipid Exchange between Borrelia burgdorferi and Host Cells

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Lipid Exchange between Borrelia burgdorferi and Host Cells

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Cholesterol can remain free in the membrane or can be internalized and glycosylated by undetermined enzymes (22). Subsequently, cholesterol glycolipids are exported to the membrane, where they form lipid rafts (23,24) that are cholesterol-rich domains with a selective presence of lipoproteins (25).…”

mentioning

confidence: 99%

Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

Toledo¹,

Monzón²,

Coleman

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE-and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.cholesterol | Lyme disease | relapsing fever | Borrelia | tick-borne C holesterol is an essential structural component of the cell membrane of vertebrate animals, and it is required for membrane integrity and fluidity. In addition to being a component of the membrane, cholesterol is the precursor of steroid hormones and bile. In eukaryotic cells, cholesterol and sphingolipids are the main components of membrane microdomains known as lipid rafts. These microdomains are characterized as being more tightly packed than the surrounding bilayer and enriched with proteins involved in signaling (1-3).In the bloodstream of humans and other vertebrates, cholesterol is transported in lipoprotein complexes. Apolipoprotein E (apoE) binds cholesterol for transport through the circulatory system as apoE-containing chylomicrons and very-low-density lipoprotein (VLDL) particles. These apoE-cholesterol particles are internalized through the interaction with the low-density lipoprotein receptors (LDLRs). LDLR is one of the cell-surface receptors in cells that binds to apoE to clear the lipoprotein particles from the blood (4). Both apoE-deficient (apoE − ) and LDLR-deficient (LDLR − ) mice show elevated serum cholesterol levels and develop atherosclerotic plaques (5, 6). These mice are the most used mouse models for hyperlipidemia and atherosclerosis research.Lyme disease and relapsing-fever Borrelia have very distinct infection courses and niches in the host. In experimental mouse infections, relapsing-fever borre...

show abstract

“…B. burgdorferi not only acquires cholesterol from epithelial cells by direct contact, but it also has the ability to recruit cholesterol from host-derived vesicles (150). In both cases, the acquisition of cholesterol in B. burgdorferi is time dependent (150), and it is glycosylated by undetermined bacterial enzymes (151) to make one of the most prominent glycolipids in the spirochete membrane, cholesteryl galactoside, which can be acylated to form acylcholesteryl galactoside. The mechanism by which B. burgdorferi acquires cholesterol from the host cell has not been defined yet, but it has been hypothesized that it could be through lipid raft–lipid raft interactions between the spirochete and the host cell (150).…”

Section: Use Of Host Lipids By Extracellular Bacteriamentioning

confidence: 99%

Hijacking and Use of Host Lipids by Intracellular Pathogens

Toledo

Benach

2015

Microbiol Spectr

View full text Add to dashboard Cite

Intracellular bacteria use a number of strategies to survive, grow, multiply, and disseminate within the host. One of the most striking adaptations that intracellular pathogens have developed is the ability to utilize host lipids and their metabolism. Bacteria such as Anaplasma , Chlamydia , or Mycobacterium can use host lipids for different purposes, such as a means of entry through lipid rafts, building blocks for bacteria membrane formation, energy sources, camouflage to avoid the fusion of phagosomes and lysosomes, and dissemination. One of the most extreme examples of lipid exploitation is Mycobacterium , which not only utilizes the host lipid as a carbon and energy source but is also able to reprogram the host lipid metabolism. Likewise, Chlamydia spp. have also developed numerous mechanisms to reprogram lipids onto their intracellular inclusions. Finally, while the ability to exploit host lipids is important in intracellular bacteria, it is not an exclusive trait. Extracellular pathogens, including Helicobacter , Mycoplasma , and Borrelia , can recruit and metabolize host lipids that are important for their growth and survival. Throughout this chapter we will review how intracellular and extracellular bacterial pathogens utilize host lipids to enter, survive, multiply, and disseminate in the host.

show abstract

Functional analysis of a lipid galactosyltransferase synthesizing the major envelope lipid in the Lyme disease spirocheteBorrelia burgdorferi

Cited by 28 publications

References 37 publications

Lipid Exchange between Borrelia burgdorferi and Host Cells

Lipid Exchange between Borrelia burgdorferi and Host Cells

Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

Hijacking and Use of Host Lipids by Intracellular Pathogens

Contact Info

Product

Resources

About