Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluoroquinolones are known to chelate with di- and trivalent cations, and it has accordingly been claimed that they perturb the integrity of the outer membrane (OM) of gram-negative bacteria. So far, chelation has not been assessed in biologically relevant test systems. Therefore, we investigated the interaction of ciprofloxacin and moxifloxacin in the absence and presence of Mg2+ with whole bacteria and isolated lipopolysaccharide (LPS) from various rough mutant strains of Salmonella enterica chemotypes by applying different biophysical techniques. We found that the fluoroquinolones did not disturb the integrity of the OM and neither were incorporated into LPS monolayers nor displaced Ca2+ from LPS monolayers, suggesting that chelation of fluoroquinolones with divalent cations does not contribute to the antibacterial effect of fluoroquinolones.
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PMID:Lack of interaction of fluoroquinolones with lipopolysaccharides. 1195 1

The Salmonella ugd gene is required for the incorporation of 4-aminoarabinose in the lipopolysaccharide and resistance to the antibiotic polymyxin B. Transcription of the ugd gene is induced by Fe3+ via the PmrA-PmrB two-component system and by low Mg2+ in a process that requires the PhoP-PhoQ two-component system, the PhoP-activated PmrD protein and the PmrA-PmrB system. Here, we establish that mutation of the tolB gene promotes ugd transcription independently of both the PhoP-PhoQ and PmrA-PmrB systems. This activation is mediated by the RcsC-YojN-RcsB phosphorelay and the RcsA protein, suggesting a role for ugd in capsule synthesis. Binding sites for the RcsB, PmrA and PhoP proteins were identified in the ugd promoter. Although the PmrA-PmrB and RcsC-YojN-RcsB systems promoted ugd transcription independently of the PhoP-PhoQ system under different environmental conditions, ugd expression inside macrophages was strictly dependent on PhoP-PhoQ, suggesting that low Mg2+ is a cue for the intracellular environment.
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PMID:Control of the Salmonella ugd gene by three two-component regulatory systems. 1251 86

The aim of this study was to assess the effects of a low extracellular Mg2+ concentration and endotoxin on interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha release from, and mRNA levels in, rat alveolar macrophages. A low extracellular Mg2+ concentration enhanced the release of both cytokines, and this release was suppressed by a calcium antagonist, nifedipine. Bacterial lipopolysaccharide (LPS) also enhanced the release of both cytokines, and this enhancement was stronger in a low-Mg2+ medium than in control medium. Furthermore, LPS increased the mRNA levels of both cytokines in alveolar macrophages, and this increase was enhanced in low-Mg2+ medium. These results suggest that a low extracellular Mg2+ concentration and LPS stimulate the release of IL-1beta and TNF-alpha from rat alveolar macrophages by increasing the synthesis of both cytokines and by Ca2+ signaling pathways.
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PMID:Effects of a low extracellular magnesium concentration and endotoxin on IL-1beta and TNF-alpha release from, and mRNA levels in, isolated rat alveolar macrophages. 1263 65

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.
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PMID:Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium. 1263 66

Magnesium supplementation has been reported to prevent cardiovascular diseases through the decrease of plasma lipids and to improve endothelial function in patients with coronary artery disease. In the present work, we evaluated whether high magnesium concentrations can directly affect the function of cultured endothelial cells, which play a crucial role in maintaining the functional integrity of the vascular wall. We cultured human umbilical vein endothelial cells for various times in media containing different concentration of magnesium (range 2 to 10 mM) and compared them to the corresponding controls (1 mM Mg). High Mg concentrations stimulated endothelial proliferation, enhanced the motogenic response to angiogenic factors and attenuated the response to lipopolysaccharide (LPS). In addition, we demonstrate that high concentrations of magnesium did not modulate the levels of plasminogen activator inhibitor-1, but enhanced the synthesis of nitric oxide, in part through the up-regulation of endothelial nitric oxide synthase. Our results demonstrate a direct role of magnesium in maintaining endothelial function. We therefore anticipate that magnesium may have a protective effect against atherosclerosis and could play a role in promoting the growth of collateral vessels in chronic ischemia. Moreover, because it induces the synthesis of nitric oxide, this cation could be a helpful tool in hypertension as well as in preventing thrombosis.
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PMID:High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro. 1515 8

The biogenesis of biological membranes hinges on the coordinated trafficking of membrane lipids between distinct cellular compartments. The bacterial outer membrane enzyme PagP confers resistance to host immune defenses by transferring a palmitate chain from a phospholipid to the lipid A (endotoxin) component of lipopolysaccharide. PagP is an eight-stranded antiparallel beta-barrel, preceded by an N-terminal amphipathic alpha-helix. The active site is localized inside the beta-barrel and is aligned with the lipopolysaccharide-containing outer leaflet, but the phospholipid substrates are normally restricted to the inner leaflet of the asymmetric outer membrane. We examined the possibility that PagP activity in vivo depends on the aberrant migration of phospholipids into the outer leaflet. We find that brief addition to Escherichia coli cultures of millimolar EDTA, which is reported to replace a fraction of lipopolysaccharide with phospholipids, rapidly induces palmitoylation of lipid A. Although expression of the E. coli pagP gene is induced during Mg2+ limitation by the phoPQ two-component signal transduction pathway, EDTA-induced lipid A palmitoylation occurs more rapidly than pagP induction and is independent of de novo protein synthesis. EDTA-induced lipid A palmitoylation requires functional MsbA, an essential ATP-binding cassette transporter needed for lipid transport to the outer membrane. A potential role for the PagP alpha-helix in phospholipid translocation to the outer leaflet was excluded by showing that alpha-helix deletions are active in vivo. Neither EDTA nor Mg(2+)-EDTA stimulate PagP activity in vitro. These findings suggest that PagP remains dormant in outer membranes until Mg2+ limitation promotes the migration of phospholipids into the outer leaflet.
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PMID:Lipid trafficking controls endotoxin acylation in outer membranes of Escherichia coli. 1531 35

Amastigotes of Leishmania major have a great ability to evade destruction in host cells. This study investigated the activation in resident, inflammatory macrophages and J774 cells in vitro treated with lipopolysaccharide (LPS), soluble Leishmania antigen (SLA), calcium ionophore (CaI) and magnesium (Mg2+) alone or combined. An increase in nitric oxide (NO) production was observed in J774 or inflammatory macrophages treated with LPS alone or in combination with SLA and CaI. The same treatments did not affect the NO release by resident macrophages. There was no interference in uptake of L. major but CaI decreased intracellular proliferation of the parasite. This study demonstrated the importance of CaI in decreasing L. major proliferation inside murine macrophages while Mg2+ seemed to increase parasite proliferation. These finding may help to understand the events involved in host cells' clearance of this pathogen.
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PMID:Comparative effect of ion calcium and magnesium in the activation and infection of the murine macrophage by Leishmania major. 1551 64

Mouse Paneth cells respond to bacteria and bacterial cell surface antigens by discharging secretory granules into the lumen of small intestinal crypts (T. Ayabe et al., Nat. Immunol. 1:113-118, 2000). To investigate mechanisms regulating these responses, purified surface glycolipid molecules with known acyl chain modifications and attenuated properties were tested for the ability to stimulate Paneth cell secretion. The antigens included lipopolysaccharide (LPS) from wild-type and msbB-null Escherichia coli and phoP-null and phoP-constitutive Salmonella enterica serovar Typhimurium strains, as well as LPS, lipid A, and lipoteichoic acid from Pseudomonas aeruginosa and Listeria monocytogenes grown in Mg2+-limited media. Measurements of total secreted protein, secreted lysozyme, and the bactericidal peptide activities of collected secretions showed that the purified antigens elicited similar secretory responses from Paneth cells in mouse crypts ex vivo, regardless of glycolipid acyl chain modification. Despite their impaired Tlr4 pathway, Paneth cells in ex vivo C3H/HeJ mouse crypts released equivalent amounts of bactericidal peptide activity in response to purified bacterial antigens, including lipid A. Thus, mouse Paneth cells respond equivalently to purified bacterial cell envelope glycolipids, regardless of functional Tlr4, the structural properties of glycolipid acyl chains, or their association with virulence in humans.
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PMID:Mouse paneth cell secretory responses to cell surface glycolipids of virulent and attenuated pathogenic bacteria. 1578 76

The aim of the present study was to elucidate the effect of the macrolide antibiotic azithromycin on Pseudomonas aeruginosa. We studied the susceptibility to azithromycin in P. aeruginosa PAO1 using a killing assay. PAO1 cells at the exponential growth phase were resistant to azithromycin. In contrast, PAO1 cells at the stationary growth phase were sensitive to azithromycin. The divalent cations Mg2+ and Ca2+ inhibited this activity, suggesting that the action of azithromycin is mediated by interaction with the outer membranes of the cells, since the divalent cations exist between adjacent lipopolysaccharides (LPSs) and stabilize the outer membrane. The divalent cation chelator EDTA behaved in a manner resembling that of azithromycin; EDTA killed more PAO1 in the stationary growth phase than in the exponential growth phase. A 1-N-phenylnaphthylamine assay showed that azithromycin interacted with the outer membrane of P. aeruginosa PAO1 and increased its permeability while Mg2+ and Ca2+ antagonized this action. Our results indicate that azithromycin directly interacts with the outer membrane of P. aeruginosa PAO1 by displacement of divalent cations from their binding sites on LPS. This action explains, at least in part, the effectiveness of sub-MICs of macrolide antibiotics in pseudomonal chronic airway infection.
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PMID:Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane. 1579 15

Addition of a phosphoethanolamine (pEtN) moiety to the outer 3-deoxy-D-manno-octulosonic acid (Kdo) residue of lipopolysaccharide (LPS) in WBB06, a heptose-deficient Escherichia coli mutant, occurs when cells are grown in 5-50 mM CaCl2 (Kanipes, M. I., Lin, S., Cotter, R. J., and Raetz, C. R. H. (2001) J. Biol. Chem. 276, 1156-1163). A Ca2+-induced, membrane-bound enzyme was responsible for the transfer of the pEtN unit to the Kdo domain. We now report the identification of the gene encoding the pEtN transferase. E. coli yhjW was cloned and overexpressed, because it is homologous to a putative pEtN transferase implicated in the modification of the beta-chain heptose residue of Neisseria meningitidis lipo-oligosaccharide (Mackinnon, F. G., Cox, A. D., Plested, J. S., Tang, C. M., Makepeace, K., Coull, P. A., Wright, J. C., Chalmers, R., Hood, D. W., Richards, J. C., and Moxon, E. R. (2002) Mol. Microbiol. 43, 931-943). In vitro assays with Kdo2-4'-[32P]lipid A as the acceptor showed that YhjW (renamed EptB) utilizes phosphatidylethanolamine in the presence of Ca2+ to transfer the pEtN group. Stoichiometric amounts of diacylglycerol were generated during the EptB-catalyzed transfer of pEtN to Kdo2-lipid A. EptB is an inner membrane protein of 574 amino acid residues with five predicted trans-membrane segments within its N-terminal region. An in-frame replacement of eptB with a kanamycin resistance cassette rendered E. coli WBB06 (but not wild-type W3110) hypersensitive to CaCl2 at 5 mM or higher. Ca2+ hypersensitivity was suppressed by excess Mg2+ in the medium or by restoring the LPS core of WBB06. The latter was achieved by reintroducing the waaC and waaF genes, which encode LPS heptosyl transferases I and II, respectively. Our data demonstrate that pEtN modification of the outer Kdo protected cells containing heptose-deficient LPS from damage by high concentrations of Ca2+. Based on its sequence similarity to EptA(PmrC), we propose that the active site of EptB faces the periplasmic surface of the inner membrane.
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PMID:A phosphoethanolamine transferase specific for the outer 3-deoxy-D-manno-octulosonic acid residue of Escherichia coli lipopolysaccharide. Identification of the eptB gene and Ca2+ hypersensitivity of an eptB deletion mutant. 1579 27


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