The search for<i>Brachyspira</i>outer membrane proteins that interact with the host

Trott, Darren J.; Alt, David P.; Zuerner, Richard L.; Wannemuehler, Michael J.; Stanton, Thad B.

doi:10.1079/ahrr200112

Cited by 36 publications

(26 citation statements)

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“…They also have noncholesterol glycolipids, monogalactosyl-diacylglycerol in B. burgdorferi and monoglucosyl-diacylglycerol in relapsing-fever Borrelia, as well as many lipoproteins (7)(8)(9)(10)(11)(12)(13)(14)(15). The presence of cholesterol is not common among prokaryotes, but it is increasingly being reported in bacterial pathogens other than Borrelia spp., including species of Helicobacter, Mycoplasma, Ehrlichia, Anaplasma, and Brachyspira (16)(17)(18)(19)(20).…”

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.

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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...

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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.

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“…Attachment occurs to mature apical enterocytes between crypt units but not to immature cells deeper in the crypts (112). B. pilosicoli surface lipoproteins may be involved in facilitating this attachment by undergoing protein-protein interactions with specific receptors on the cell surface (52). If a sufficient number of cells become attached, this gives the appearance of a "false brush border."…”

Section: Pathogenesismentioning

confidence: 99%

“…A number of specific outer membrane proteins and lipoproteins of B. pilosicoli have been described (52), but more work is needed to define their potential role in disease, including whether or not they may be involved in important functions such as attachment and/or in generating protective immunity. Recently, exposed proteins on the cell surface and peptides and proteins in extracellular growth medium were characterized using a high-resolution Orbitrap instrument with multiple liquid chromatography-tandem mass spectrometry (LC-MS/MS) runs (53).…”

Section: Cell Surface Propertiesmentioning

confidence: 99%

The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans

Hampson

2018

Clin Microbiol Rev

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SUMMARY Brachyspira pilosicoli is a slow-growing anaerobic spirochete that colonizes the large intestine. Colonization occurs commonly in pigs and adult chickens, causing colitis/typhlitis, diarrhea, poor growth rates, and reduced production. Colonization of humans also is common in some populations (individuals living in village and peri-urban settings in developing countries, recent immigrants from developing countries, homosexual males, and HIV-positive patients), but the spirochete rarely is investigated as a potential human enteric pathogen. In part this is due to its slow growth and specialized growth requirements, meaning that it is not detectable in human fecal samples using routine diagnostic methods. Nevertheless, it has been identified histologically attached to the colon and rectum in patients with conditions such as chronic diarrhea, rectal bleeding, and/or nonspecific abdominal discomfort, and one survey of Australian Aboriginal children showed that colonization was significantly associated with failure to thrive. B. pilosicoli has been detected in the bloodstream of elderly patients or individuals with chronic conditions such as alcoholism and malignancies. This review describes the spirochete and associated diseases. It aims to encourage clinicians and clinical microbiologists to consider B. pilosicoli in their differential diagnoses and to develop and use appropriate diagnostic protocols to identify the spirochete in clinical specimens.

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“…However, cholesterol, presumably acquired from the host or environment, is present in bacteria such as Mycoplasma, Ehrlichia, Anaplasma, Brachyspira, Helicobacter, and Borrelia (14)(15)(16)(17)(18). In addition, other bacteria have molecules with cholesterol-like properties (e.g., hopanoids), and may use them to form membrane microdomains (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Ordered Membrane Domain-Forming Properties of the Lipids of Borrelia burgdorferi

Huang

Toledo

Benach

et al. 2016

Biophysical Journal

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Co-existing disordered and ordered (raft) membrane domains exist in Borrelia burgdorferi, the causative agent of Lyme disease. However, although B. burgdorferi contains cholesterol lipids, it lacks sphingolipids-a crucial component of rafts in eukaryotes. To define the principles of ordered lipid domain formation in Borrelia, the domain forming properties of vesicles composed of its three major lipids, acylated cholesteryl galactoside (ACGal), monogalactosyl diacyglycerol (MGalD), and phosphatidylcholine (PC) and/or their mixtures were studied. Anisotropy and fluorescence resonance energy transfer measurements were used to assay membrane order and ordered-domain formation. ACGal had the highest potential to form ordered domains. Interestingly, mixtures of ACGal with B. burgdorferi PC formed ordered domains more readily than mixtures of ACGal with MGalD. This appears to reflect the relatively high level of saturation observed for B. burgdorferi PC, as vesicles containing ACGal and PC, but in which the unsaturated lipid dioleoyl PC was substituted for Borrelia PC, failed to form ordered domains. In addition, the properties of ACGal were compared to those of cholesterol. Depending on what other lipids were present, ordered-domain formation in the presence of ACGal was greater than or equal to that in the presence of cholesterol. Giant unilamellar vesicles formed from ACGal-containing mixtures showed rounded domain shapes similar to those in analogous vesicles containing cholesterol, indicative of liquid-ordered state rather than solid-like gel-state domain formation. Over all, principles of ordered-domain formation in B. burgdorferi appear to be very similar to those in eukaryotes, with saturated PC taking the place of sphingolipids, but with ACGal being the main lipid component inducing ordered-domain formation.

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The search forBrachyspiraouter membrane proteins that interact with the host

Cited by 36 publications

References 50 publications

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

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

The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans

Ordered Membrane Domain-Forming Properties of the Lipids of Borrelia burgdorferi

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