Phase behavior, supramolecular structure, and molecular conformation of lipopolysaccharide

Seydel, Ulrich; Labischinski, Harald; Kastowsky, Manfred; Brandenburg, Klaus

doi:10.1016/s0171-2985(11)80339-6

Cited by 101 publications

(60 citation statements)

References 45 publications

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“…However, antibiotic sensitivity in vivo is a very complex process (4,5,9,27,48) and may not be a function only of the membrane permeation property. Besides, the importance of fatty acyl chains attached to the lipid A moiety of LPS in membrane barrier function cannot be ignored (1,28,39,40,41,49,52). The fatty acyl chains of lipid A in Salmonella, Proteus, and Chromobacterium spp.…”

Section: Discussionmentioning

confidence: 99%

“…The chemical structures of lipid A from various bacteria such as Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella minnesota, Salmonella typhimurium, Shigella sonnei, Yersinia pestis, Er-winia carotovora, and Haemophilus ducreyi are remarkably identical in that they have a backbone of 3-1',6-glucosamine (GlcNAc) (19,32). Heterogeneity of lipid A arises because of variation in the fatty acid composition, which appears to vary depending on the bacterial strain and growth conditions (6,11,21,25,39,40,41,49,52). The composition of the core oligosaccharide is also variable; this oligosaccharide is generally composed of 2-keto-3-deoxyoctonic acid, heptose, glucose, and galactose.…”

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confidence: 99%

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Phosphorylation of lipopolysaccharides in the Antarctic psychrotroph Pseudomonas syringae: a possible role in temperature adaptation

1994

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Phosphorylation of lipopolysaccharide (LPS) from a psychrotrophic bacterium, Pseudomonas syringae, from Antarctica was studied by using sucrose gradient-separated membrane fractions. The bacterium was found to possess an LPS kinase which could phosphorylate more LPS postsynthetically at higher temperatures. The phosphorylation was low at a lower temperature and was also found to occur in vivo. After phosphorylation of LPS in vitro, it was found that the major part of the radioactivity (>85%) was associated with the core oligosaccharide region of the LPS. The phosphate groups of this region are probably involved in the binding of metal ions, which could be removed by EDTA. The cells grown at the lower temperature probably contained fewer divalent cations because of the smaller amount of phosphate and thereby were more sensitive to EDTA. The cells were also more sensitive to cationic antibiotics at the lower temperature. A possible role of this differential phosphorylation of LPS in modulating the function of the outer membrane as a permeability barrier in the psychrotroph is discussed.The outermost layer of the outer membrane bilayer of gram-negative bacteria is composed of lipopolysaccharides (LPS) which contain a hydrophobic moiety, lipid A, and a polysaccharide moiety consisting of the so-called core oligosaccharide and 0 polysaccharide. The chemical structures of lipid A from various bacteria such as Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella minnesota, Salmonella typhimurium, Shigella sonnei, Yersinia pestis, Er-winia carotovora, and Haemophilus ducreyi are remarkably identical in that they have a backbone of 3-1',6-glucosamine (GlcNAc) (19,32). Heterogeneity of lipid A arises because of variation in the fatty acid composition, which appears to vary depending on the bacterial strain and growth conditions (6,11,21,25,39,40,41,49,52). The composition of the core oligosaccharide is also variable; this oligosaccharide is generally composed of 2-keto-3-deoxyoctonic acid, heptose, glucose, and galactose. The structure of the 0 polysaccharide is most variable, and the 0 polysaccharide may contain various unusual sugars (32,38). The other striking feature of LPS is the presence of a high level of phosphorus (2 to 5.6%), which is attached either to the core sugars (such as 2-keto-3-deoxyoctonic acid and heptose) or to GlcNAc of lipid A as ethanolamine phosphate, ethanolamine PPi, PP1, or simply phosphate (13,25,38,51).Although much information about LPS composition and structure has accumulated during the last 25 years, very little is known about the physiological function of LPS. LPS have been studied as toxins and virulence factors of gram-negative bacteria that cause pathogenesis in animals and plants (19,32). However, the function of LPS with respect to the physiology of the bacteria is poorly understood. In bacteria, LPS has been implicated in providing a kind of permeation barrier for hydrophobic compounds to move across the membrane. The evidence for this has come from the study of...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Phosphorylation of lipopolysaccharides in the Antarctic psychrotroph Pseudomonas syringae: a possible role in temperature adaptation

1994

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“…5 The lipophilic portion of LPS, known as lipid A, is the active component. 6 In an aqueous environment, LPS exists as polymeric aggregates, with the hydrophilic polysaccharide component facing outward, and the lipid A region facing inward.…”

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confidence: 99%

Potentiation of Lipopolysaccharide-Induced Chemokine and Adhesion Molecule Expression in Corneal Fibroblasts by Soluble CD14 or LPS-Binding Protein

Fukuda¹,

Kumagai

Yamamoto

et al. 2005

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The detection of bacterial lipopolysaccharide (LPS) by human cells is facilitated by LPS-binding protein (LBP) and soluble (s)CD14. The effects of these proteins on chemokine release and adhesion molecule expression in cultured human corneal fibroblasts were examined. METHODS. The release of chemokines into culture supernatants and the expression of the intercellular adhesion molecule (ICAM)-1 on the cell surface were determined by enzymelinked immunosorbent assays. The intracellular abundance of chemokine and ICAM-1 mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analyses. The phosphorylation and degradation of IB-␣ and the subcellular localization of NF-B were examined by immunoblot and immunofluorescence analyses, respectively. RESULTS. Neither sCD14 nor LBP alone affected the expression of chemokines or ICAM-1 in cultured human corneal fibroblasts. However, sCD14 or LBP enhanced the LPS-induced upregulation of ICAM-1 and the chemokines interleukin-8 and monocyte chemoattractant protein (MCP)-1 in these cells at the protein and mRNA levels. B acterial corneal ulcer is a major cause of loss of vision in developed and developing countries. This condition results from the destruction of collagen fibrils in the corneal stroma by collagenolytic enzymes produced as a consequence of bacterial infection.1 Pathologic examination has revealed the presence of many infiltrating leukocytes, including neutrophils and macrophages, in or surrounding corneal ulcers. 1 We have shown that the interaction of resident corneal fibroblasts with infiltrating leukocytes very likely promotes collagen degradation.2 Whereas corneal fibroblasts alone in culture degrades collagen fibrils to a small extent, neutrophils alone do not. However, the addition of either neutrophils or neutrophilconditioned medium to corneal fibroblasts results in a marked increase in the amount of collagen degraded by the fibroblasts. We have also demonstrated an interaction between bacteria and corneal fibroblasts in culture, in that elastase produced by Pseudomonas aeruginosa both degrades collagen directly and activates the collagen-degrading matrix metalloproteinases produced by corneal fibroblasts.3 In addition, we found that corneal fibroblasts are able to detect the presence of lipopolysaccharide (LPS), a component of the cell membrane of Gramnegative bacteria, and that they upregulate the expression of the chemokines interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 and that of intercellular adhesion molecule (ICAM)-1 in response.4 Such a response in vivo would be expected to trigger the local infiltration of leukocytes. Corneal fibroblasts may thus function as sentinel and effector cells in the defense of the cornea against bacterial infection.LPS is an amphipathic molecule with a large hydrophobic component and a small hydrophilic domain. 5 The lipophilic portion of LPS, known as lipid A, is the active component. 6 In an aqueous environment, LPS exists as polymeric aggregates, with the hydro...

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“…Synthesis of the novel series of compounds presented here was undertaken based on observations regarding supramolecular aggregates that are formed by a variety of lipid As in aqueous media. Studies by Brandenburg et al (Seydel et al, 1993) demonstrated that lipid As, which are biological antagonists, form lamellar structures, whereas the agonistic lipid As such as E. coli lipid A are found to form cubic and cubichexagonal supramolecular structures. In an unrelated study, Krisovitch and Regen (1992) analyzed artificial membranes that were composed of phospholipid dimers that were found to have a lamellar supramolecular form.…”

Section: Discussionmentioning

confidence: 99%

A Novel Class of Endotoxin Receptor Agonists with Simplified Structure, Toll-Like Receptor 4-Dependent Immunostimulatory Action, and Adjuvant Activity

Hawkins

Ishizaka²,

McGuinness³

et al. 2002

J Pharmacol Exp Ther

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A series of novel, synthetic compounds containing lipids linked to a phosphate-containing acyclic backbone are shown to have similar biological properties to lipopolysaccharide (LPS). These compounds showed intrinsic agonistic properties when tested for their ability to stimulate tumor necrosis factor-␣ in human whole blood and interleukin-6 in U373 human glioblastoma cells without added LPS coreceptor CD14. The presence of the LPS antagonist E5564 completely blocked responses, suggesting that the novel compounds and LPS share a common mechanism of cell activation. Stereoselectivity of the molecules was observed in vitro; compounds with an R,R,R,R-configuration were strongly agonistic, whereas compounds with an R,S,S,R-configuration were much weaker in their activity on human whole blood and U373 cells. We also tested the effect of the compounds in cells transfected with the LPS receptor Tolllike receptor 4 (TLR4), with similar results, further supporting a shared mechanism with LPS. This was confirmed in vivo where the agonists failed to elicit cytokine responses in C3H/HeJ mice lacking TLR4 signaling. Because LPS-like molecules enhance immune responses, the compounds were mixed with tetanus toxoid and administered to mice in an immunization protocol to test for adjuvant activity. They enhanced the generation of specific antibodies against tetanus toxoid. Our results indicate that these unique compounds behave as agonists of TLR4, resulting in responses similar to those elicited by LPS. They display adjuvant activity in vivo and may be useful for the development of vaccine therapies.

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Phase behavior, supramolecular structure, and molecular conformation of lipopolysaccharide

Cited by 101 publications

References 45 publications

Phosphorylation of lipopolysaccharides in the Antarctic psychrotroph Pseudomonas syringae: a possible role in temperature adaptation

Phosphorylation of lipopolysaccharides in the Antarctic psychrotroph Pseudomonas syringae: a possible role in temperature adaptation

Potentiation of Lipopolysaccharide-Induced Chemokine and Adhesion Molecule Expression in Corneal Fibroblasts by Soluble CD14 or LPS-Binding Protein

A Novel Class of Endotoxin Receptor Agonists with Simplified Structure, Toll-Like Receptor 4-Dependent Immunostimulatory Action, and Adjuvant Activity

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