Lipid Exchange between Borrelia burgdorferi and Host Cells

Crowley, Jameson T.; Toledo, Álvaro; LaRocca, Timothy J.; Coleman, James L.; London, Erwin; Benach, Jorge L.

doi:10.1371/journal.ppat.1003109

Cited by 109 publications

(116 citation statements)

References 92 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the remainder of the culture filtrate after depletion of MV by ultracentrifugation contained much less LpqH and SodC, and the levels of these proteins in the soluble fraction were comparable in the two strains. To detect MV released into the culture fluid, we used the lipophilic probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), which fluoresces in hydrophobic environments but not in aqueous environments (32) and has been used to detect MV in Borrelia burgdorferi culture supernatants (33). By the DPH assay, VirR-deficient Mtb released 1.5-fold more lipid than WT Mtb, whereas the complemented strain released less than half as much as WT (Fig.…”

Section: Virr Regulates Release Of Immunomodulatory Factorsmentioning

confidence: 99%

Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis

Rath

Huang

Wang

et al. 2013

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

119

View full text Add to dashboard Cite

Mycobacterium tuberculosis (Mtb) restrains immune responses well enough to escape eradication but elicits enough immunopathology to ensure its transmission. Here we provide evidence that this host-pathogen relationship is regulated in part by a cytosolic, membrane-associated protein with a unique structural fold, encoded by the Mtb gene rv0431. The protein acts by regulating the quantity of Mtb-derived membrane vesicles bearing Toll-like receptor 2 ligands, including the lipoproteins LpqH and SodC. We propose that rv0431 be named "vesiculogenesis and immune response regulator." TLR2 | macrophages

show abstract

Section: Virr Regulates Release Of Immunomodulatory Factorsmentioning

confidence: 99%

Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis

Rath

Huang

Wang

et al. 2013

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

119

View full text Add to dashboard Cite

show abstract

“…Recently, we demonstrated that B. burgdorferi acquires cholesterol from host cells (21). Cholesterol can remain free in the membrane or can be internalized and glycosylated by undetermined enzymes (22).…”

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.

Self Cite

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

“…Recently, a spate of studies on the regulatory networks of B. burgdorferi have added several layers of complexity to the molecular mechanisms that connect external signal recognition to appropriate host-specific adaptation in its disparate hosts (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Expression of several key lipoproteins of B. burgdorferi such as outer surface protein C (OspC) and decorin binding proteins A and B (DbpA/B) that contribute to vertebrate host infection were shown to be dependent on the Rrp2-RpoN-RpoS pathway (20)(21)(22)(23).…”

mentioning

confidence: 99%

Contributions of Environmental Signals and Conserved Residues to the Functions of Carbon Storage Regulator A of Borrelia burgdorferi

et al. 2013

View full text Add to dashboard Cite

Carbon storage regulator A of Borrelia burgdorferi (CsrA Bb ) contributes to vertebrate host-specific adaptation by modulating activation of the Rrp2-RpoN-RpoS pathway and is critical for infectivity. We hypothesized that the functions of CsrA Bb are dependent on environmental signals and on select residues. We analyzed the phenotype of csrA Bb deletion and site-specific mutants to determine the conserved and pathogen-specific attributes of CsrA Bb

show abstract

Lipid Exchange between Borrelia burgdorferi and Host Cells

Cited by 109 publications

References 92 publications

Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis

Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis

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

Contributions of Environmental Signals and Conserved Residues to the Functions of Carbon Storage Regulator A of Borrelia burgdorferi

Contact Info

Product

Resources

About