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Structure type: oligomer
Trivial name: pentaacyl monophosphoryl lipid A
Compound class: LPS, lipid A, glycolipid
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531

• Article ID: 1435
  Alexander C, Zähringer U "Chemical structure of lipid A - the primary immunomodulatory center of bacterial lipopolysaccharides" - Trends in Glycoscience and Glycotechnology 14(76) (2002) 69-86
  

  Lipopolysaccharides (LPS) are the major outer surface membrane components expressed by the vast majority of Gram-negative bacteria and have been identified to be extremely strong stimulators of innate or natural immunity in diverse eukaryotic species ranging from insects or plants to humans. Due to early observations on the induction of severe pathological forms of immunoactivation such as septic shock this class of bacterial surface molecules has been termed ‘endotoxins’. By combination of chemical analysis, mass spectrometry and NMR techniques, the chemical structures of LPS from a variety of Gram-negative bacteria have been characterized in detail. LPS consist of an extracellular poly- or oligosaccharide region that is anchored in the outer bacterial membrane by a specific glycolipid termed lipid A. The lipid A component has been identified to be the primary immunostimulatory center of LPS. An overview of major types of lipid A structures recently established is given, thus completing and updating previous reviews (1, 2). In the present review central structure-bioactivity-correlations are discussed with respect to immunoactivation of the mammalian phagocyte system. In addition to the classical group of strongly agonistic (highly endotoxic) forms of lipid A, several natural or synthetic lipid A structures have been identified that display comparatively low or even no phagocyte activation for a given mammalian species. Some members of the latter more heterogeneous group are capable to antagonize the effects of strongly stimulatory LPS/lipid A. LPS of Gram-negative bacteria have been found to express a certain degree of structural diversity with respect to three structural elements: the glycosyl part of lipid A (lipid A backbone), the number, charge and linkage of polar head-group substituents, and the number, position and chemical nature of various acyl residues directly or indirectly linked to the lipid A backbone. Among all these structural variations, the acylation pattern has been found to encode mostly for its strong agonistic or antagonistic immunostimulatory activities in various biosystems.

  Lipopolysaccharide, lipid A, variability, antagonists, immunomodulatory activity

  Publication DOI: 10.4052/tigg.14.69
  Journal NLM ID: 9425898
  Correspondence: uzaehr@fz-borstel.de
  Institutions: Research Center Borstel, Center of Medicine and Bio-Sciences Department of Immunochemistry and Biochemical Microbiology
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 31316 (all data & tools)
• Article ID: 1671
  Zähringer U, Lindner B, Rietschel ET "Molecular structure of Lipid A, the endotoxic center of bacterial lipopolysaccharides" - Advances in Carbohydrate Chemistry and Biochemistry 50 (1994) 211-276
  

  No abstract available

  Lipopolysaccharide, lipid A, glycolipid

  NCBI PubMed ID: 7942255
  Publication DOI: 10.1016/S0065-2318(08)60152-3
  Journal NLM ID: 0240537
  Institutions: Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, D-23845 Borstel, Germany, Department of Immunochemistry and Biochemical Microbiology, Forschungsinstitut Borstel, Germany
  
   
  
  Rhodobacter sphaeroides ATCC 17023
  CSDB ID 100601 (all data & tools)
• Article ID: 3041
  Moran AP "Structure-bioactivity relationships of bacterial endotoxins" - Journal of Toxicology. Toxin Reviews 14 (1995) 47-83
  

  Endotoxins, chemically lipopolysaccharides (LPS), are major components of the cell envelope of Gram-negative bacteria which are an important contributing factor to septic shock, in general, and Gram-negative septic shock, in particular. The structure of the lipid moiety of LPS, lipid A, has been intensively investigated in Escherichia coli and Salmonella spp. and based on the structural data, synthetic compounds prepared. In general, these compounds exhibit identical endotoxic activities compared with bacterial lipid A and LPS, thus confirming that lipid A is the endotoxic center of LPS. Analysis of lipid A from various Gram-negative bacterial species showed that lipid A is a family of (phospho)glycolipid molecules that are closely related in general architecture, but whose fine structure varies. The various structures of selected lipid As of different bacterial species are reviewed in this article and the influence of their structure on endotoxicity is discussed. The resulting Deductions on structure-bioactivity relationships from the latter studies is supported and extended by investigations on the bioactivity (endotoxicity) of synthetic lipid A analogs and partial structures. In particular, endotoxicity is not dependent on one lipid A constituent, i.e., a toxophore group, but it is a unique molecular structure, a peculiar surpramolecular conformation, which allows optimal expression of endotoxicity activity. Furthermore, LPS is not a direct toxin, rather endotoxic shock is a syndrome that results from the host's own response to LPS whereby there is systemic release of endogenous substances (cytokines) that control the cascade of events leading to shock. Considerable advances have been made in understanding the specific interaction of endotoxin with serum proteins and monocyte/macrophage-bound recognition molecules. Since this is the central event of endotoxin activity leading to endotoxic shock, therapeutic approaches have been proposed blocking this event.

  Publication DOI: 10.3109/15569549509089968
  Journal NLM ID: 8300146
  Publisher: New York, NY: Marcel Dekker
  Institutions: Department of Microbiology, University College, Galway, Ireland, Department of Microbiology, National University College, University Road, Galway, Ireland
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 141959 (all data & tools)
• Article ID: 4188
  Qureshi N, Honovich JP, Hara H, Cotter RJ, Takayama K "Location of fatty acids in lipid A obtained from lipopolysaccharide of Rhodopseudomonas sphaeroides ATCC 17023" - Journal of Biological Chemistry 263 (1988) 5502-5504
  

  Monophosphoryl lipid A (MLA) obtained from the lipopolysaccharide of Rhodopseudomonas sphaeroides ATCC 17023 was initially purified by silicic acid column chromatography to yield a single major pentaacyl MLA fraction. This fraction was methylated and further purified by reverse-phase high performance liquid chromatography to yield three prominent peak fractions. Laser desorption mass spectrometry of these three fractions allowed us to complete the important structural analysis of lipid A from this source. Three structurally distinct forms of dimethyl MLA were identified where Mr = 1447, 1449, and 1451 atomic mass units. These forms differed only by the presence or absence of unsaturation and keto group in the fatty acids. We established that the acyloxyacyl group (either δ 7-tetradecenoyloxytetradecanoate or tetradecanoyloxytetradecanoate) and the 3-ketotetradecanoate or hydroxytetradecanoate occupied the 2'- and 2-positions of the glucosamine disaccharide, respectively. Analysis of several minor fractions suggests that there is considerable structural heterogeneity in the MLA. With this new knowledge, the study of the structure-to-function relationship of the reported lack of toxicity of lipopolysaccharide from R. sphaeroides can be completed.

  NCBI PubMed ID: 3258599
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Institutions: Mycobacteriology Research Laboratory, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705
  
   
  
  Rhodopseudomonas sphaeroides ATCC 17023
  CSDB ID 135271 (all data & tools)
• Article ID: 4212
  Fagan MA, Liu Y, Stutz P, Vyplel H, Golenbock DT "Acyclic analogue of lipid A stimulates TNF-alpha and arachidonate release via a unique LPS-signaling pathway" - Journal of Immunology 153 (1994) 5230-5238
  

  LPS has been implicated in the pathogenesis of Gram-negative bacterial sepsis. Despite intensive efforts to define the LPS-signal transduction pathway, CD14 is the sole molecule clearly demonstrated to possess signaling capabilities. However, it remains unclear whether CD14 is the only LPS-signaling molecule expressed in phagocytes and how CD14-mediated signaling occurs. Compound SDZ 280.961 is a synthetic triacylated amino acid that structurally resembles the reducing sugar moiety of lipid A. SDZ 280.961 effectively stimulated TNF-alpha release from human PBMC. Co-incubation of PBMC with the specific LPS inhibitor Rhodobacter sphaeroides lipid A inhibited SDZ 280.961-mediated stimulation of TNF-alpha release, indicating that this analogue signals mononuclear cells via a LPS-activated signaling pathway. Induction of TNF-alpha release from mononuclear cells by SDZ 280.961 was strongly dependent on the presence of serum and was enabled by the presence of purified LPS-binding protein, characteristics of CD14-mediated signaling. In contrast, SDZ 280.961-mediated signaling was not inhibited by blocking anti-CD14 mAbs. A Chinese hamster ovary fibroblast line transfected with human CD14, which responds to LPS in a manner qualitatively similar to that of macrophage cell lines, failed to respond to SDZ 280.961. Taken together, these data suggest that the lipid A analogue SDZ 280.961 activates monocytes via a unique LPS-signal transduction pathway that appears to be independent of CD14.

  NCBI PubMed ID: 7525728
  Journal NLM ID: 2985117R
  Publisher: Bethesda, MD: American Association of Immunologists
  Institutions: Department of Internal Medicine, Maxwell Finland Laboratory for Infectious Diseases, Boston City Hospital, Boston University School of Medicine, MA 02118
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 140153 (all data & tools)
• Article ID: 5064
  Cochet F, Peri F "The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling" - International Journal of Molecular Sciences 18(11) (2017) 2318
  

  The interactions between sugar-containing molecules from the bacteria cell wall and pattern recognition receptors (PRR) on the plasma membrane or cytosol of specialized host cells are the first molecular events required for the activation of higher animal's immune response and inflammation. This review focuses on the role of carbohydrates of bacterial endotoxin (lipopolysaccharide, LPS, lipooligosaccharide, LOS, and lipid A), in the interaction with the host Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) complex. The lipid chains and the phosphorylated disaccharide core of lipid A moiety are responsible for the TLR4 agonist action of LPS, and the specific interaction between MD-2, TLR4, and lipid A are key to the formation of the activated complex (TLR4/MD-2/LPS)₂, which starts intracellular signalling leading to nuclear factors activation and to production of inflammatory cytokines. Subtle chemical variations in the lipid and sugar parts of lipid A cause dramatic changes in endotoxin activity and are also responsible for the switch from TLR4 agonism to antagonism. While the lipid A pharmacophore has been studied in detail and its structure-activity relationship is known, the contribution of core saccharides 3-deoxy-d-manno-octulosonic acid (Kdo) and heptosyl-2-keto-3-deoxy-octulosonate (Hep) to TLR4/MD-2 binding and activation by LPS and LOS has been investigated less extensively. This review focuses on the role of lipid A, but also of Kdo and Hep sugars in LPS/TLR4 signalling.

  Lipopolysaccharide, TLR4 (Toll-like receptor 4), MD-2 (myeloid differentiation factor 2), Kdo (3-deoxy-d-manno-octulosonic acid)

  NCBI PubMed ID: 29099761
  Publication DOI: 10.3390/ijms18112318
  Journal NLM ID: 101092791
  Publisher: Basel, Switzerland: MDPI
  Correspondence: f.cochet@campus.unimib.it; rancesco.peri@unimib.it
  Institutions: Department of Biotechnology and Biosciences, University of Milano Bicocca, Piazza della Scienza, 2, 20126 Milano, Italy
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 12340 (all data & tools)
• Article ID: 5875
  Zamyatina A, Heine H "Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways" - Frontiers in Immunology 11 (2020) 585146
  

  The innate immune response to lipopolysaccharide is essential for host defense against Gram-negative bacteria. In response to bacterial infection, the TLR4/MD-2 complex that is expressed on the surface of macrophages, monocytes, dendritic, and epithelial cells senses picomolar concentrations of endotoxic LPS and triggers the production of various pro-inflammatory mediators. In addition, LPS from extracellular bacteria which is either endocytosed or transfected into the cytosol of host cells or cytosolic LPS produced by intracellular bacteria is recognized by cytosolic proteases caspase-4/11 and hosts guanylate binding proteins that are involved in the assembly and activation of the NLRP3 inflammasome. All these events result in the initiation of pro-inflammatory signaling cascades directed at bacterial eradication. However, TLR4-mediated signaling and caspase-4/11-induced pyroptosis are largely involved in the pathogenesis of chronic and acute inflammation. Both extra- and intracellular LPS receptors-TLR4/MD-2 complex and caspase-4/11, respectively-are able to directly bind the lipid A motif of LPS. Whereas the structural basis of lipid A recognition by the TLR4 complex is profoundly studied and well understood, the atomic mechanism of LPS/lipid A interaction with caspase-4/11 is largely unknown. Here we describe the LPS-induced TLR4 and caspase-4/11 mediated signaling pathways and their cross-talk and scrutinize specific structural features of the lipid A motif of diverse LPS variants that have been reported to activate caspase-4/11 or to induce caspase-4/11 mediated activation of NLRP3 inflammasome (either upon transfection of LPS in vitro or upon infection of cell cultures with intracellular bacteria or by LPS as a component of the outer membrane vesicles). Generally, inflammatory caspases show rather similar structural requirements as the TLR4/MD-2 complex, so that a 'basic' hexaacylated bisphosphorylated lipid A architecture is sufficient for activation. However, caspase-4/11 can sense and respond to much broader variety of lipid A variants compared to the very 'narrow' specificity of TLR4/MD-2 complex as far as the number and the length of lipid chains attached at the diglucosamine backbone of lipid A is concerned. Besides, modification of the lipid A phosphate groups with positively charged appendages such as phosphoethanolamine or aminoarabinose could be essential for the interaction of lipid A/LPS with inflammatory caspases and related proteins.

  lipid A, chemical structure, molecular recognition, inflammation, innate immunity, aminoarabinose, LR4/MD-2, structural basis

  NCBI PubMed ID: 33329561
  Publication DOI: 10.3389/fimmu.2020.585146
  Journal NLM ID: 101560960
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: alla.zamyatina@boku.ac.at
  Institutions: Institute of Organic Chemistry, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria, Research Group Innate Immunity, Research Center Borstel-Leibniz Lung Center, Airway Research Center North (ARCN), German Center for Lung Disease (DZL), Borstel, Germany
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 7692 (all data & tools)
• Article ID: 6049
  Di Lorenzo F, Duda KA, Lanzetta R, Silipo A, De Castro C, Molinaro A "A Journey from Structure to Function of Bacterial Lipopolysaccharides" - Chemical Reviews (2021)
  

  Lipopolysaccharide (LPS) is a crucial constituent of the outer membrane of most Gram-negative bacteria, playing a fundamental role in the protection of bacteria from environmental stress factors, in drug resistance, in pathogenesis, and in symbiosis. During the last decades, LPS has been thoroughly dissected, and massive information on this fascinating biomolecule is now available. In this Review, we will give the reader a third millennium update of the current knowledge of LPS with key information on the inherent peculiar carbohydrate chemistry due to often puzzling sugar residues that are uniquely found on it. Then, we will drive the reader through the complex and multifarious immunological outcomes that any given LPS can raise, which is strictly dependent on its chemical structure. Further, we will argue about issues that still remain unresolved and that would represent the immediate future of LPS research. It is critical to address these points to complete our notions on LPS chemistry, functions, and roles, in turn leading to innovative ways to manipulate the processes involving such a still controversial and intriguing biomolecule.

  Lipopolysaccharide, LPS, structure, Pathogenesis, carbohydrate, function, gram negative bacteria

  NCBI PubMed ID: 34286971
  Publication DOI: 10.1021/acs.chemrev.0c01321
  Journal NLM ID: 2985134R
  Publisher: Chem Rev
  Correspondence: Antonio Molinaro
  Institutions: Department of Chemical Sciences, University of Naples Federico II, via Cinthia 4, 80126 Naples, Italy, Task Force on Microbiome Studies, University of Naples Federico II, Via Cinthia 4, 80126 Naples, Italy, Research Center Borstel Leibniz Lung Center, Parkallee 4a, 23845 Borstel, Germany, Department of Agricultural Sciences, University of Naples Federico II, Via Universita 96, 80055 Portici, Naples, Italy, Department of Chemistry, School of Science, Osaka University, 1-1 Osaka University Machikaneyama, Toyonaka, Osaka 560-0043, Japan
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 7947 (all data & tools)
• Article ID: 6385
  Fux AC, Casonato Melo C, Michelini S, Swartzwelter BJ, Italiani P, Himly M "Heterogeneity of Lipopolysaccharide as Source of Variability in Bioassays and LPS-Binding Proteins as Remedy" - International Journal of Molecular Sciences 24(9) (2023) 8395
  

  Lipopolysaccharide (LPS), also referred to as endotoxin, is the major component of Gram-negative bacteria's outer cell wall. It is one of the main types of pathogen-associated molecular patterns (PAMPs) that are known to elicit severe immune reactions in the event of a pathogen trespassing the epithelial barrier and reaching the bloodstream. Associated symptoms include fever and septic shock, which in severe cases, might even lead to death. Thus, the detection of LPS in medical devices and injectable pharmaceuticals is of utmost importance. However, the term LPS does not describe one single molecule but a diverse class of molecules sharing one common feature: their characteristic chemical structure. Each bacterial species has its own pool of LPS molecules varying in their chemical composition and enabling the aggregation into different supramolecular structures upon release from the bacterial cell wall. As this heterogeneity has consequences for bioassays, we aim to examine the great variability of LPS molecules and their potential to form various supramolecular structures. Furthermore, we describe current LPS quantification methods and the LPS-dependent inflammatory pathway and show how LPS heterogeneity can affect them. With the intent of overcoming these challenges and moving towards a universal approach for targeting LPS, we review current studies concerning LPS-specific binders. Finally, we give perspectives for LPS research and the use of LPS-binding molecules.

  Lipopolysaccharide, lipid A, immunology, endotoxin, detection, low endotoxin recovery, LPS-binding molecules

  NCBI PubMed ID: 37176105
  Publication DOI: 10.3390/ijms24098395
  Journal NLM ID: 101092791
  Publisher: Basel, Switzerland: MDPI
  Correspondence: M. Himly
  Institutions: Division of Allergy & Immunology, Department of Biosciences & Medical Biology, Paris Lodron University of Salzburg (PLUS), Hellbrunnerstra?e 34, 5020 Salzburg, Austria, Chemical Biology Department, R&D Reagents, Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Straße 68, 51429 Bergisch Gladbach, Germany, Biotechnical Faculty, Department of Biology, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia, Department of Microbiology, Immunology, and Pathology, 1601 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA, Experimental Medical Physics, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany, Institute of Biochemistry and Cell Biology, Consiglio Nazionale delle Ricerche (CNR), Via P. Castellino 111, 80131 Naples, Italy, Stazione Zoologica Anton Dohrn (SZN), Villa Comunale, 80121 Naples, Italy
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 10683 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531

• Article ID: 1446
  Kaltashov IA, Doroshenko V, Cotter RJ, Takayama K, Qureshi N "Confirmation of the structure of lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides by a combination of MALDI, LSIMS, and tandem mass spectrometry" - Analytical Chemistry 69 (1997) 2317-2322
  

  The chemical structure of nontoxic diphosphoryl lipid A from Rhodobacter sphaeroides was confirmed using a combination of LSIMS (on a two-sector mass spectrometer) and MALDI (on time-of-flight and ion trap mass spectrometers) in conjunction with tandem mass spectrometry in both positive and negative ion modes. Accurate molecular weight measurement accompanied by the analysis of fragment ion masses yielded the composition of fatty acyl groups. Tandem experiments (collisionally induced dissociation of both quasimolecular and oxonium ions) were also performed, revealing the precise location and nature of the fatty acyl groups on the disaccharide backbone.

  Lipopolysaccharide, structure, lipid A, MALDI, tandem, Rhodobacter, Rhodobacter sphaeroides

  NCBI PubMed ID: 9212704
  Journal NLM ID: 0370536
  Institutions: Middle Atlantic Mass Spectrometry Laboratory, Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
  Methods: MS/MS, MALDI-TOF MS, LSI-MS
  
   
  
  Rhodobacter sphaeroides ATCC 17023
  CSDB ID 835 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531

• Article ID: 1479
  Rose JR, Christ WJ, Brisson JR, Kawata T, Rossignol DP "Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: Comparison with activities of synthetic material of the proposed structure and analogs" - Infection and Immunity 63 (1995) 833-839
  

  Lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) has been previously shown to antagonize many of the effects of endotoxins from more pathogenic gram-negative bacteria. We have reported on the synthesis of the proposed structure of RSLA and determined that bacterially derived RSLA is not identical to its proposed structure (W.J. Christ, P. D. McGuinness, O. Asano, Y. Wang, M. A. Mullarkey, M. Perez, L. D. Hawkins, T. A. Blythe, G. R. Dubuc, and A. L. Robidoux, J. Am. Chem. Soc. 116:3637-3638, 1994). Here we report results of analyzing the antagonistic and agonistic activities of bacterially derived RSLA in comparison with the activities of chemically synthesized material of the proposed structure of RSLA and analogs. Results indicated that all compounds were approximately equally potent at inhibiting endotoxin-induced release of tumor necrosis factor alpha from human monocytes and human whole blood as well as endotoxin-induced generation of nitric oxide in murine macrophages. In addition, all compounds were of equivalent potencies at inhibiting the binding of 125I-labelled lipopolysaccharide derivatized with 2-(p-azido-salicylamido) ethyl-1-3'-dithiopropionate to murine macrophages. Higher concentrations of bacterially derived RSLA (10 to 100 microM) were agonistic in human and murine assays. In gamma interferon-treated murine macrophages, agonism was exhibited at concentrations as low as 100 nM. In contrast, all synthetic materials were either dramatically less agonistic or devoid of agonistic activity when tested at concentrations as high as 100 microM. It is possible either that bacterially derived RSLA contains a small amount of a highly agonistic impurity or that the agonistic activity of RSLA is intrinsic to its molecular structure. In either case, these biological results support our previous report concluding that biologically derived RSLA is not identical to synthetic material of its proposed structure.

  structure, lipid, lipid A, activity, antagonist, comparison, Synthetic, Rhodobacter, Rhodobacter sphaeroides, agonist

  NCBI PubMed ID: 7868254
  Journal NLM ID: 0246127
  Publisher: American Society for Microbiology
  Correspondence: dan_rossignol@eisai.com
  Institutions: Section of Biology, Eisai Research Institute, Andover, Massachusetts 01810-2441, Tsukuba Research Laboratories, Eisai Co. Ltd., Tsukuba, Japan
  Methods: TNF-a assays, biological assays, HPLC
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 4368 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531

• Article ID: 1479
  Rose JR, Christ WJ, Brisson JR, Kawata T, Rossignol DP "Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: Comparison with activities of synthetic material of the proposed structure and analogs" - Infection and Immunity 63 (1995) 833-839
  

  Lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) has been previously shown to antagonize many of the effects of endotoxins from more pathogenic gram-negative bacteria. We have reported on the synthesis of the proposed structure of RSLA and determined that bacterially derived RSLA is not identical to its proposed structure (W.J. Christ, P. D. McGuinness, O. Asano, Y. Wang, M. A. Mullarkey, M. Perez, L. D. Hawkins, T. A. Blythe, G. R. Dubuc, and A. L. Robidoux, J. Am. Chem. Soc. 116:3637-3638, 1994). Here we report results of analyzing the antagonistic and agonistic activities of bacterially derived RSLA in comparison with the activities of chemically synthesized material of the proposed structure of RSLA and analogs. Results indicated that all compounds were approximately equally potent at inhibiting endotoxin-induced release of tumor necrosis factor alpha from human monocytes and human whole blood as well as endotoxin-induced generation of nitric oxide in murine macrophages. In addition, all compounds were of equivalent potencies at inhibiting the binding of 125I-labelled lipopolysaccharide derivatized with 2-(p-azido-salicylamido) ethyl-1-3'-dithiopropionate to murine macrophages. Higher concentrations of bacterially derived RSLA (10 to 100 microM) were agonistic in human and murine assays. In gamma interferon-treated murine macrophages, agonism was exhibited at concentrations as low as 100 nM. In contrast, all synthetic materials were either dramatically less agonistic or devoid of agonistic activity when tested at concentrations as high as 100 microM. It is possible either that bacterially derived RSLA contains a small amount of a highly agonistic impurity or that the agonistic activity of RSLA is intrinsic to its molecular structure. In either case, these biological results support our previous report concluding that biologically derived RSLA is not identical to synthetic material of its proposed structure.

  structure, lipid, lipid A, activity, antagonist, comparison, Synthetic, Rhodobacter, Rhodobacter sphaeroides, agonist

  NCBI PubMed ID: 7868254
  Journal NLM ID: 0246127
  Publisher: American Society for Microbiology
  Correspondence: dan_rossignol@eisai.com
  Institutions: Section of Biology, Eisai Research Institute, Andover, Massachusetts 01810-2441, Tsukuba Research Laboratories, Eisai Co. Ltd., Tsukuba, Japan
  Methods: TNF-a assays, biological assays, HPLC
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 31302 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_176772

• Article ID: 1491
  Zähringer U, Lindner B, Rietschel ET "Chemical structure of lipid A: recent advances in structural analysis of biologically active molecules" - Book: Endotoxin in Health and Disease (1999) 93-114
  

  no abstract available

  lipopolysaccharides, core, lipid A, O-polysaccharide, endotoxin, structural analysis, stucture

  WWW link: https://books.google.ru/books?id=oWhqhK1cE-gC&pg=PA93&lpg=PA93&dq=Chemical+structure+of+lipid+A:+recent+advances+in+structural+analysis+of+biologically+active+molecules&source=bl&ots=7h9_ecjijZ&sig=Pe0bcz2OlOZp_CZx135g91R0yHw&hl=ru&sa=X&ved=0ahUKEwiyr_j05pjNAhXICiwKHSptB2UQ6AEIGzAA#v=onepage&q=Chemical%20structure%20of%20lipid%20A%3A%20recent%20advances%20in%20structural%20analysis%20of%20biologically%20active%20molecules&f=false
  Publisher: New York, Marcel Dekker, Inc.
  Editors: Brade H, Opal SM, Vogel SN, Morrison DC
  Institutions: Research Center Borstel, Borstel, Germany
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 31463 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1417.9 [M-H]-
Compound class: LOS
Contained glycoepitopes: IEDB_141807,IEDB_151531

• Article ID: 5453
  Kanie Y, Yamaguchi Y, Hayashi A, Uzawa J, Hatakeyama M, Hidaka Y, Toda N, Nakamura S, Kanie O "Structural analysis of a novel lipooligosaccharide (LOS) from Rhodobacter azotoformans" - Carbohydrate Research 473 (2019) 104-114
  

  Lipopolysaccharides (LPS) are components of the Gram-negative bacterial cell surface that stimulate the host innate immune system through the Toll-like receptor (TLR) 4-MD-2 complex. Rhodobacter sp. have been reported to produce LPS that lack endotoxic activity, and instead act as antagonists of other endotoxins. In this report, we focused on LPS, especially the lipooligosaccharide (LOS) fraction produced by Rhodobacter azotoformans that shows production of IL-8, but has an inverse correlation with IL-6 production. We analyzed their molecular structure by using mass spectrometry and nuclear magnetic resonance spectroscopy and report a novel LOS consisting of a shorter glycan structure containing glucuronic acid but not heptoses. A novel glycan structure, Glc α(1→4)GlcA α(1→4)KDO α(2→4)[Glc α(1→5)]KDO α(2→6)[4-phosphate]GlcN β(1→6)GlcN α1-phosphate, was proposed using NMR methods. The structure was consistent with one obtained based on MS. The MS analysis further revealed the existence of structural variation caused by extension with hexoses. The acyl composition in lipid A was suggested to contain three C14 fatty acyl chains (3-OH-14:0 or 3-oxo-14:0at N2 of GlcN-1, 3-OH-14:0at N2 of GlcN-2, that carried another 14:1 ∆7 on its beta-hydroxyl group) and two C10 fatty acyl chains (3-OH-10:0at O3 of both GlcN), which are same as those found in lipid A from Rhodobacter sphaeroides.

  NMR, structure elucidation, mass spectrometry, glucuronic acid, lipopolysaccharide (LPS)

  NCBI PubMed ID: 30658251
  Publication DOI: 10.1016/j.carres.2018.12.018
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: O. Kanie
  Institutions: Department of Applied Biochemistry, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan, Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan, TFK Co., Ltd, 1-2-25-D407 Wadayamadori, Hyogo-ku, Kobe, Hyogo, 652-0884, Japan, Nakamura Laboratory, RIKEN Baton Zone Program, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan
  Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, sugar analysis, TLC, 31P NMR, acid hydrolysis, MS/MS, GPC, alkaline hydrolysis, hydrazinolysis, ESI-IT-MS, SEC
  
   
  
  Rhodobacter azotoformans BP0899
  CSDB ID 788 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: LOS
Contained glycoepitopes: IEDB_115136,IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_140630,IEDB_141807,IEDB_142488,IEDB_144998,IEDB_144999,IEDB_146664,IEDB_150908,IEDB_151531,IEDB_241118,IEDB_983931,SB_192

• Article ID: 5453
  Kanie Y, Yamaguchi Y, Hayashi A, Uzawa J, Hatakeyama M, Hidaka Y, Toda N, Nakamura S, Kanie O "Structural analysis of a novel lipooligosaccharide (LOS) from Rhodobacter azotoformans" - Carbohydrate Research 473 (2019) 104-114
  

  Lipopolysaccharides (LPS) are components of the Gram-negative bacterial cell surface that stimulate the host innate immune system through the Toll-like receptor (TLR) 4-MD-2 complex. Rhodobacter sp. have been reported to produce LPS that lack endotoxic activity, and instead act as antagonists of other endotoxins. In this report, we focused on LPS, especially the lipooligosaccharide (LOS) fraction produced by Rhodobacter azotoformans that shows production of IL-8, but has an inverse correlation with IL-6 production. We analyzed their molecular structure by using mass spectrometry and nuclear magnetic resonance spectroscopy and report a novel LOS consisting of a shorter glycan structure containing glucuronic acid but not heptoses. A novel glycan structure, Glc α(1→4)GlcA α(1→4)KDO α(2→4)[Glc α(1→5)]KDO α(2→6)[4-phosphate]GlcN β(1→6)GlcN α1-phosphate, was proposed using NMR methods. The structure was consistent with one obtained based on MS. The MS analysis further revealed the existence of structural variation caused by extension with hexoses. The acyl composition in lipid A was suggested to contain three C14 fatty acyl chains (3-OH-14:0 or 3-oxo-14:0at N2 of GlcN-1, 3-OH-14:0at N2 of GlcN-2, that carried another 14:1 ∆7 on its beta-hydroxyl group) and two C10 fatty acyl chains (3-OH-10:0at O3 of both GlcN), which are same as those found in lipid A from Rhodobacter sphaeroides.

  NMR, structure elucidation, mass spectrometry, glucuronic acid, lipopolysaccharide (LPS)

  NCBI PubMed ID: 30658251
  Publication DOI: 10.1016/j.carres.2018.12.018
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: O. Kanie
  Institutions: Department of Applied Biochemistry, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan, Structural Glycobiology Team, Systems Glycobiology Research Group, RIKEN Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan, TFK Co., Ltd, 1-2-25-D407 Wadayamadori, Hyogo-ku, Kobe, Hyogo, 652-0884, Japan, Nakamura Laboratory, RIKEN Baton Zone Program, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan
  Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, sugar analysis, TLC, 31P NMR, acid hydrolysis, MS/MS, GPC, alkaline hydrolysis, hydrazinolysis, ESI-IT-MS, SEC
  
   
  
  Rhodobacter azotoformans BP0899
  CSDB ID 789 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531

• Article ID: 6082
  Kawahara K "Variation, Modification and Engineering of Lipid A in Endotoxin of Gram-Negative Bacteria" - International Journal of Molecular Sciences 22(5) (2021) 2281
  

  Lipid A of Gram-negative bacteria is known to represent a central role for the immunological activity of endotoxin. Chemical structure and biosynthetic pathways as well as specific receptors on phagocytic cells had been clarified by the beginning of the 21st century. Although the lipid A of enterobacteria including Escherichia coli share a common structure, other Gram-negative bacteria belonging to various classes of the phylum Proteobacteria and other taxonomical groups show wide variety of lipid A structure with relatively decreased endotoxic activity compared to that of E. coli. The structural diversity is produced from the difference of chain length of 3-hydroxy fatty acids and non-hydroxy fatty acids linked to their hydroxyl groups. In some bacteria, glucosamine in the backbone is substituted by another amino sugar, or phosphate groups bound to the backbone are modified. The variation of structure is also introduced by the enzymes that can modify electrostatic charges or acylation profiles of lipid A during or after its synthesis. Furthermore, lipid A structure can be artificially modified or engineered by the disruption and introduction of biosynthetic genes especially those of acyltransferases. These technologies may produce novel vaccine adjuvants or antagonistic drugs derived from endotoxin in the future.

  Lipopolysaccharide, lipid A, endotoxin, chemical structure, fatty acid, engineering

  NCBI PubMed ID: 33668925
  Publication DOI: 10.3390/ijms22052281
  Journal NLM ID: 101092791
  Publisher: Basel, Switzerland: MDPI
  Correspondence: kawahara@kanto-gakuin.ac.jp
  Institutions: Department of Biosciences, College of Science and Engineering, Kanto Gakuin University, Yokohama, Kanagawa 236-8501, Japan
  
   
  
  Rhodobacter sphaeroides
  CSDB ID 5864 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1724.25 [M-H]-
C₉₅H₁₇₇N₄O₂₀P
Compound class: lipid A

• Article ID: 6444
  Pětrošová H, Mikhael A, Culos S, Giraud-Gatineau A, Gomez AM, Sherman ME, Ernst RK, Cameron CE, Picardeau M, Goodlett DR "Lipid A structural diversity among members of the genus Leptospira" - Frontiers in Microbiology 14 (2023) 1181034
  

  Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.

  pathogenicity, lipid A, mass spectrometry, structure-activity relationship, Molecular typing, lipopolysaccharide (LPS), fast lipid analysis technique, Leptospira

  NCBI PubMed ID: 37303810
  Publication DOI: 10.3389/fmicb.2023.1181034
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: H. Pětrošová : D.R. Goodlett
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada, University of Victoria Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC, Canada, Institut Pasteur, Université Paris Cite, CNRS UMR 6047, Biology of Spirochetes Unit, Paris, France, Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States, Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States
  Methods: MALDI-MS, MS/MS, fast lipid analysis technique (FLAT)
  
   
  
  Leptospira interrogans L495 (P1hv), Leptospira noguchii 201102933 (P1hv), Leptospira weilii 14535 (P1hv)
  CSDB ID 22295 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1696.22 [M-H]-
C₉₃H₁₇₁N₄O₂₀P
Compound class: lipid A

• Article ID: 6444
  Pětrošová H, Mikhael A, Culos S, Giraud-Gatineau A, Gomez AM, Sherman ME, Ernst RK, Cameron CE, Picardeau M, Goodlett DR "Lipid A structural diversity among members of the genus Leptospira" - Frontiers in Microbiology 14 (2023) 1181034
  

  Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.

  pathogenicity, lipid A, mass spectrometry, structure-activity relationship, Molecular typing, lipopolysaccharide (LPS), fast lipid analysis technique, Leptospira

  NCBI PubMed ID: 37303810
  Publication DOI: 10.3389/fmicb.2023.1181034
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: H. Pětrošová : D.R. Goodlett
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada, University of Victoria Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC, Canada, Institut Pasteur, Université Paris Cite, CNRS UMR 6047, Biology of Spirochetes Unit, Paris, France, Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States, Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States
  Methods: MALDI-MS, MS/MS, fast lipid analysis technique (FLAT)
  
   
  
  Leptospira adleri M7A (P1lv), Leptospira ainazelensis 201903074 10/E/19 (P1lv), Leptospira dzianensis M12A (P1lv), Leptospira gomenensis KG8-B22 (P1lv), Leptospira tipperaryensis GWTS1 (P1lv)
  CSDB ID 26005 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1668.14 [M-H]-
Compound class: lipid A

• Article ID: 6444
  Pětrošová H, Mikhael A, Culos S, Giraud-Gatineau A, Gomez AM, Sherman ME, Ernst RK, Cameron CE, Picardeau M, Goodlett DR "Lipid A structural diversity among members of the genus Leptospira" - Frontiers in Microbiology 14 (2023) 1181034
  

  Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.

  pathogenicity, lipid A, mass spectrometry, structure-activity relationship, Molecular typing, lipopolysaccharide (LPS), fast lipid analysis technique, Leptospira

  NCBI PubMed ID: 37303810
  Publication DOI: 10.3389/fmicb.2023.1181034
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: H. Pětrošová : D.R. Goodlett
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada, University of Victoria Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC, Canada, Institut Pasteur, Université Paris Cite, CNRS UMR 6047, Biology of Spirochetes Unit, Paris, France, Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States, Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States
  Methods: MALDI-MS, MS/MS, fast lipid analysis technique (FLAT)
  
   
  
  Leptospira fluminis SCS5 (P2)
  CSDB ID 26007 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1614.15 [M-H]-
Compound class: lipid A

• Article ID: 6444
  Pětrošová H, Mikhael A, Culos S, Giraud-Gatineau A, Gomez AM, Sherman ME, Ernst RK, Cameron CE, Picardeau M, Goodlett DR "Lipid A structural diversity among members of the genus Leptospira" - Frontiers in Microbiology 14 (2023) 1181034
  

  Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.

  pathogenicity, lipid A, mass spectrometry, structure-activity relationship, Molecular typing, lipopolysaccharide (LPS), fast lipid analysis technique, Leptospira

  NCBI PubMed ID: 37303810
  Publication DOI: 10.3389/fmicb.2023.1181034
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: H. Pětrošová : D.R. Goodlett
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada, University of Victoria Genome British Columbia Proteomics Center, University of Victoria, Victoria, BC, Canada, Institut Pasteur, Université Paris Cite, CNRS UMR 6047, Biology of Spirochetes Unit, Paris, France, Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States, Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, United States
  Methods: MALDI-MS, MS/MS, fast lipid analysis technique (FLAT)
  
   
  
  Leptospira perolatii FH1-B-B1 (P2)
  CSDB ID 26008 (all data & tools)