Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: 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
  
   
  
  Flavobacterium meningosepticum
  CSDB ID 31318 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: 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
  
   
  
  Flavobacterium meningosepticum
  CSDB ID 31319 (all data & tools)

Show legend Show as text

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

• Article ID: 1447
  Kato H, Haishima Y, Iida T, Tanaka A, Tanamoto K "Chemical structure of lipid A isolated from Flavobacterium meningosepticum lipopolysaccharide" - Journal of Bacteriology 180(15) (1998) 3891-3899
  

  The chemical structure of the lipid A of the lipopolysaccharide component isolated from Flavobacterium meningosepticum IFO 12535 was elucidated. Methylation and nuclear magnetic resonance analyses showed that two kinds of hydrophilic backbone exist in the free lipid A: a β(1→6)-linked 2-amino-2-deoxy-D-glucose, which is usually present in enterobacterial lipid A's, and a 2-amino-6-O-(2, 3-diamino-2,3-dideoxy-β-D-glucopyranosyl)-2-deoxy-D-glucose, in a molar ratio of 1.00:0.35. Both backbones were α-glycosidically phosphorylated in position 1, and the hydroxyl groups at positions 4, 4', and 6' were unsubstituted. Liquid secondary ion-mass spectrometry revealed a pseudomolecular ion at m/z 1673 [M-H]- as a major monophosphoryl lipid A component carrying five acyl groups. Fatty acid analysis showed that the lipid A contained 1 mol each of amide-linked (R)-3-OH iC17:0, ester-linked (R)-3-OH iC15:0, amide-linked (R)-3-O-(iC15:0)-iC17:0, and both amide- and ester-linked (R)-3-OH C16:0. Fatty acid distribution analyses using several mass spectrometry determinations demonstrated that the former two constituents were distributed on positions 2 and 3 of the reducing terminal unit of the backbones and that the latter two were attached to the 2' and 3' positions in the nonreducing terminal residue.

  Lipopolysaccharide, structure, lipid, lipid A, chemical, chemical structure, Flavobacterium

  NCBI PubMed ID: 9683486
  Journal NLM ID: 2985120R
  Publisher: American Society for Microbiology
  Correspondence: tanamoto@nihs.go.jp
  Institutions: Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158,1and, Department of Drug Analysis, Showa College of Pharmaceutical Sciences, Machida, Tokyo 194,2 Japan
  Methods: 13C NMR, 1H NMR, methylation, GLC-MS, de-O-acylation, 31P NMR, GLC, FAB-MS/MS, composition analysis, LSI-MS
  
   
  
  Flavobacterium meningosepticum
  CSDB ID 850 (all data & tools)

Show legend Show as text

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

• Article ID: 1447
  Kato H, Haishima Y, Iida T, Tanaka A, Tanamoto K "Chemical structure of lipid A isolated from Flavobacterium meningosepticum lipopolysaccharide" - Journal of Bacteriology 180(15) (1998) 3891-3899
  

  The chemical structure of the lipid A of the lipopolysaccharide component isolated from Flavobacterium meningosepticum IFO 12535 was elucidated. Methylation and nuclear magnetic resonance analyses showed that two kinds of hydrophilic backbone exist in the free lipid A: a β(1→6)-linked 2-amino-2-deoxy-D-glucose, which is usually present in enterobacterial lipid A's, and a 2-amino-6-O-(2, 3-diamino-2,3-dideoxy-β-D-glucopyranosyl)-2-deoxy-D-glucose, in a molar ratio of 1.00:0.35. Both backbones were α-glycosidically phosphorylated in position 1, and the hydroxyl groups at positions 4, 4', and 6' were unsubstituted. Liquid secondary ion-mass spectrometry revealed a pseudomolecular ion at m/z 1673 [M-H]- as a major monophosphoryl lipid A component carrying five acyl groups. Fatty acid analysis showed that the lipid A contained 1 mol each of amide-linked (R)-3-OH iC17:0, ester-linked (R)-3-OH iC15:0, amide-linked (R)-3-O-(iC15:0)-iC17:0, and both amide- and ester-linked (R)-3-OH C16:0. Fatty acid distribution analyses using several mass spectrometry determinations demonstrated that the former two constituents were distributed on positions 2 and 3 of the reducing terminal unit of the backbones and that the latter two were attached to the 2' and 3' positions in the nonreducing terminal residue.

  Lipopolysaccharide, structure, lipid, lipid A, chemical, chemical structure, Flavobacterium

  NCBI PubMed ID: 9683486
  Journal NLM ID: 2985120R
  Publisher: American Society for Microbiology
  Correspondence: tanamoto@nihs.go.jp
  Institutions: Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158,1and, Department of Drug Analysis, Showa College of Pharmaceutical Sciences, Machida, Tokyo 194,2 Japan
  Methods: 13C NMR, 1H NMR, methylation, GLC-MS, de-O-acylation, 31P NMR, GLC, FAB-MS/MS, composition analysis, LSI-MS
  
   
  
  Flavobacterium meningosepticum
  CSDB ID 31651 (all data & tools)

Show legend Show as text

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

• 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
  
   
  
  Bacteroides fragilis
  CSDB ID 31459 (all data & tools)

Show legend Show as text

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

• 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
  
   
  
  Bacteroides fragilis
  CSDB ID 31460 (all data & tools)

Show legend Show as text

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

• 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
  
   
  
  Bacteroides fragilis NCTC 9434
  CSDB ID 100585 (all data & tools)

Show legend Show as text

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

• Article ID: 2984
  Weintraub A, Zähringer U, Wollenweber HW, Seydel U, Rietschel ET "Structural characterization of the lipid A component of Bacteroides fragilis strain NCTC 9343 lipopolysaccharide" - European Journal of Biochemistry 183 (1989) 425-431
  

  The chemical structure of Bacteroides fragilis NCTC 9343 lipid A was characterized by using conventional chemical procedures, methylation analysis, and laser desorption mass spectrometry. It was found that B. fragilis lipid A consists of a β-D-glucosaminyl-(1-6)-D-glucosaminyl-1-O-phosphate backbone whose hydroxyl groups in positions 4, 4' and 6' are free, the latter serving as the attachment site for the polysaccharide component in lipopolysaccharide. This backbone molecule carries up to of five molecules of ester- and amide-bound long chain non-hydroxylated and (R)-3-hydroxy fatty acids. With regard to the distribution on the fatty acids on the lipid A backbone, a considerable heterogeneity was revealed by laser desorption mass spectrometry. Despite this heterogeneity, a major species of B. fragilis lipid A could be defined in which the hydroxyl group at position 3' of the distal GlcN carries (R)-3-hydroxyhexadecanoic acid and the hydroxyl group at position 3 of the reducing GlcN is acylated by (R)-3-hydroxypentadecanoic acid. The amino group of the distal GlcN residue carries (R)-3-(13-methyltetradecanoyloxy)-15-methylhexadecanoic acid and that of the reducing GlcN group (R)-3-hydroxyhexadecanoic acid. The absence of ester-bound phosphate and ester-linked 3-acyloxyacyl groups, the presence of not more than five acyl residues and the predominance of fatty acids possessing 15-17 carbon atoms are unique features of B. fragilis lipid A which differentiate it from enterobacterial and other lipids A and which are likely to be related to its low endotoxic activity.

  NCBI PubMed ID: 2759091
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Institutions: Department of Clinical Bacteriology, Karolinska Institute, Huddinge University Hospital
  
   
  
  Bacteroides fragilis NCTC 9343
  CSDB ID 123325 (all data & tools)
• Article ID: 5085
  Ma H, Cummins DD, Edelstein NB, Gomez J, Khan A, Llewellyn MD, Picudella T, Willsey SR, Nangia S "Modeling Diversity in Structures of Bacterial Outer Membrane Lipids" - Journal of Chemical Theory and Computation 13(2) (2017) 811-824
  

  Lipopolysaccharides (LPSs) are vital components of the outer membrane of Gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A, a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structures and their immunogenic potencies. In this work, we model the lipid A structures of eight commensal or human pathogenic bacterial species: Helicobacter pylori, Porphyromonas gingivalis, Bacteroides fragilis, Bordetella pertussis, Chlamydia trachomatis, Campylobacter jejuni, Neisseria meningitidis, and Salmonella minnesota. The membrane properties of these bacterial species were characterized and compared using molecular simulations. The structure-property relationships that emerge from this lipid A molecular library highlight the roles of acyl chain lengths, number of chains, phosphorylation state, membrane composition, and counterion charge in regulating the phase transition temperature of the membrane, diffusion coefficient of the lipids, and membrane thickness. The molecular and structural insights provided reveal the diversity in bacterial outer membrane lipids and their contribution to human disease and immunity.

  Lipopolysaccharide, lipid A, outer membrane

  NCBI PubMed ID: 28080049
  Publication DOI: 10.1021/acs.jctc.6b00856
  Journal NLM ID: 101232704
  Publisher: Washington, DC: American Chemical Society
  Correspondence: snangia@syr.edu
  Institutions: Department of Biomedical and Chemical Engineering, Syracuse University , Syracuse, New York 13244, United States
  Methods: MD simulations, molecular mechanics
  
   
  
  Bacteroides fragilis
  CSDB ID 12404 (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
  
   
  
  Bacteroides fragilis NCTC 9343
  CSDB ID 22388 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: LPS
Contained glycoepitopes: IEDB_141807,IEDB_151531

• 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
  
   
  
  Bacteroides fragilis
  CSDB ID 141962 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 1688.25
Compound class: lipid A
Contained glycoepitopes: IEDB_141807,IEDB_151531

• Article ID: 5162
  Jacobson AN, Choudhury BP, Fischbach MA "The Biosynthesis of Lipooligosaccharide from Bacteroides thetaiotaomicron" - mBio 9(2) (2018) e02289-17
  

  Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides, makes up around 50% of the cells in a typical Western gut; these cells harbor similar to 300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants. We demonstrate, inter alia, that the glycan does not appear to have a repeating unit, and so this strain produces lipooligosaccharide (LOS) rather than LPS. This result contrasts with Bacteroides vulgatus ATCC 8482, which by SDS-PAGE analysis appears to produce LPS with a repeating unit. Additionally, our identification of the B. thetaiotaomicron LOS oligosaccharide gene cluster allowed us to identify similar clusters in other Bacteroides species. Our work lays the foundation for developing a structure-function relationship for Bacteroides LPS/LOS in the context of host colonization. IMPORTANCE Much is known about the bacterial species and genes that make up the human microbiome, but remarkably little is known about the molecular mechanisms through which the microbiota influences host biology. A well-known mechanism by which bacteria influence the host centers around lipopolysaccharide (LPS), a component of the Gram-negative bacterial outer membrane. Pathogen-derived LPS is a potent ligand for host receptor Toll-like receptor 4, which plays an important role in sensing bacteria as part of the innate immune response. Puzzlingly, the most common genus of human gut bacteria, Bacteroides, produces LPS but does not elicit a potent proinflammatory response. Previous work showing that Bacteroides LPS differs structurally from pathogen-derived LPS suggested the outlines of an explanation. Here, we take the next step, elucidating the biosynthetic pathway for Bacteroides LPS and generating mutants in the process that will be of great use in understanding how this molecule modulates the host immune response.

  Lipopolysaccharide, biosynthesis, Lipooligosaccharide, Bacteroides, microbiome

  Publication DOI: 10.1128/mBio.02289-17
  Journal NLM ID: 101519231
  Publisher: Washington, DC: American Society for Microbiology
  Correspondence: fischbach@fischbachgroup.org
  Institutions: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, California, USA, Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, California, USA, GlycoAnalytics Core, University of California, San Diego, California, USA
  Methods: PCR, SDS-PAGE, MALDI-TOF MS, genetic methods, function analysis of gene clusters
  
   
  
  Bacteroides thetaiotaomicron VPI 5482, Bacteroides fragilis NCTC 9343, Bacteroides ovatus ATCC 8343, Bacteroides uniformis ATCC 8492, Bacteroides vulgatus ATCC 8482
  CSDB ID 12616 (all data & tools)

Show legend Show as text

Structure type: oligomer ; 887.5594 [M+Na]+
C₄₅H₈₄O₁₅
Compound class: glycolipid
Contained glycoepitopes: IEDB_130701,IEDB_144983,IEDB_152206,IEDB_164174,IEDB_983930,SB_197,SB_44,SB_67,SB_72

• Article ID: 5607
  Bultel-Poncé V, Debitus C, Berge JP, Cerceau C, Guyot M "Metabolites from the sponge-associated bacterium Micrococcus luteus" - Journal of Marine Biotechnology 6(4) (1998) 233-236
  

  In an ongoing survey of the bioactive potential of microorganisms associated with marine invertebrates, the extract of the sponge-associated bacterial strain Micrococcus luteus was found to exhibit potent antimicrobial activity. The previously known synthetic 2,4,4'-trichloro-2'-hydroxydiphenylether was found to be responsible for the antimicrobial activity. The major metabolite isolated was a new acyl-1-(acyl-6'-mannobiosyl)-3-glycerol

  glycolipid, Micrococcus luteus, glycerolipid

  NCBI PubMed ID: 9852617
  Journal NLM ID: 9309765
  Publisher: New York, NY: Springer International
  Correspondence: guyot@mnhn.fr
  Institutions: Laboratoire de Chimie des Substances Naturelles du Museum National d’Histoire Naturelle, associé au CNRS, Paris, France, ORSTOM, Noumea, New Caledonia
  Methods: 13C NMR, 1H NMR, EI-MS, IR, TLC, UV, extraction, optical rotation measurement, CC, cell growth, melting point determination, sonication, antimicrobial assay, centrifugation, HR-FAB-MS
  
   
  
  Micrococcus luteus
  CSDB ID 47754 (all data & tools)
• Article ID: 5673
  Bultel-Poncé V, Debitus C, Blond A, Cerceau C, Guyot M "Lutoside: an acyl-1-(acyl-6′-mannobiosyl)-3-glycerol isolated from the sponge-associated bacterium Micrococcus luteus" - Tetrahedron Letters 38(33) (1997) 5805-5808
  

  Lutoside, an unusual acyl-1-(acyl-6′-mannobiosyl)-3-glycerol 1 was isolated from the sponge-associated bacterial strain Microccocus luteus. Sructure elucidation was performed by sprectroscopic analysis and chemical transformations

  glycolipid, Micrococcus luteus, glycerolipid, lutoside

  Publication DOI: 10.1016/S0040-4039(97)01283-5
  Journal NLM ID: 2984819R
  Publisher: Elsevier
  Correspondence: guyot@mnhn.fr
  Institutions: Laboratoire de Chimie des Substances Naturelles du Museum National d’Histoire Naturelle, associé au CNRS, Paris, France, ORSTOM, Noumea, New Caledonia
  Methods: 13C NMR, 1H NMR, NMR-2D, IR, enzymatic digestion, extraction, optical rotation measurement, acetylation, CC, cell growth, melting point determination, sonication, centrifugation, HR-FAB-MS
  
   
  
  Micrococcus luteus
  CSDB ID 47830 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: glycolipid
Contained glycoepitopes: IEDB_130701,IEDB_144983,IEDB_152206,IEDB_164174,IEDB_983930,SB_197,SB_44,SB_67,SB_72

• Article ID: 5673
  Bultel-Poncé V, Debitus C, Blond A, Cerceau C, Guyot M "Lutoside: an acyl-1-(acyl-6′-mannobiosyl)-3-glycerol isolated from the sponge-associated bacterium Micrococcus luteus" - Tetrahedron Letters 38(33) (1997) 5805-5808
  

  Lutoside, an unusual acyl-1-(acyl-6′-mannobiosyl)-3-glycerol 1 was isolated from the sponge-associated bacterial strain Microccocus luteus. Sructure elucidation was performed by sprectroscopic analysis and chemical transformations

  glycolipid, Micrococcus luteus, glycerolipid, lutoside

  Publication DOI: 10.1016/S0040-4039(97)01283-5
  Journal NLM ID: 2984819R
  Publisher: Elsevier
  Correspondence: guyot@mnhn.fr
  Institutions: Laboratoire de Chimie des Substances Naturelles du Museum National d’Histoire Naturelle, associé au CNRS, Paris, France, ORSTOM, Noumea, New Caledonia
  Methods: 13C NMR, 1H NMR, NMR-2D, IR, enzymatic digestion, extraction, optical rotation measurement, acetylation, CC, cell growth, melting point determination, sonication, centrifugation, HR-FAB-MS
  
   
  
  Micrococcus luteus
  CSDB ID 47831 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: LPS
Contained glycoepitopes: IEDB_130650,IEDB_136044,IEDB_136045,IEDB_136095,IEDB_136105,IEDB_137472,IEDB_137485,IEDB_137777,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_142489,IEDB_144562,IEDB_144983,IEDB_146664,IEDB_150948,IEDB_151531,IEDB_152206,IEDB_152214,IEDB_153553,IEDB_174333,IEDB_189517,IEDB_190606,IEDB_225177,IEDB_461719,IEDB_885823,IEDB_983930,IEDB_983931,SB_154,SB_165,SB_166,SB_187,SB_192,SB_195,SB_44,SB_7,SB_72,SB_86,SB_88

• Article ID: 5759
  Di Lorenzo F, Pither MD, Scarinci I, Martufi M, Guzman-Caldentey J, Lakomiec E, Jachymek W, Bruijns SCM, Santamaria SM, Frick JS, van Kooyk Y, Chiodo F, Silipo A, Bernardini ML, Molinaro A "Pairing Bacteroides vulgatus LPS Structure with Its Immunomodulatory Effects on Human Cellular Models" - ACS Central Science 6(9) (2020) 1602-1616
  

  The gut microbiota guide the development of the host immune system by setting a systemic threshold for immune activation. Lipopolysaccharides (LPSs) from gut bacteria are able to trigger systemic and local proinflammatory and immunomodulatory responses, and this capability strongly relies on their fine structures. Up to now, only a few LPS structures from gut commensals have been elucidated; therefore, the molecular motifs that may be important for LPS-mammalian cell interactions at the gut level are still obscure. Here, we report on the full structure of the LPS isolated from one of the prominent species of the genus Bacteroides, Bacteroides vulgatus. The LPS turned out to consist of a particular chemical structure based on hypoacylated and mono-phosphorylated lipid A and with a galactofuranose-containing core oligosaccharide and an O-antigen built up of mannose and rhamnose. The evaluation of the immunological properties of this LPS on human in vitro models revealed a very interesting capability to produce anti-inflammatory cytokines and to induce a synergistic action of MD-2/TLR4- and TLR2-mediated signaling pathways.

  human, Bacteroides, cytokines, LPS structure, immunomodulatory, gut microbiota

  NCBI PubMed ID: 32999936
  Publication DOI: 10.1021/acscentsci.0c00791
  Journal NLM ID: 101660035
  Publisher: Washington DC: ACS
  Correspondence: flaviana.dilorenzo@unina.it; molinaro@unina.it
  Institutions: Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy, Task Force on Microbiome Studies, University of Naples Federico II, 80126 Naples, Italy, Department of Biology and Biotechnologies 'C. Darwin', Sapienza-University of Rome, 00185 Rome, Italy, Department of Structural and Chemical Biology, Centro de Investigaciones Biologicas, CIB-CSIC, 28040 Madrid, Spain, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw 53-114, Poland, Department of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam 1081 HV, The Netherlands, Institute of Medical Microbiology and Hygiene, University of Tubingen, 72076 Tubingen, Germany
  Methods: 13C NMR, 1H NMR, GLC-MS, NMR-2D, SDS-PAGE, sugar analysis, chemical analysis, ELISA, 31P NMR, deacylation, ESI-MS, MS/MS, MALDI-TOF MS, GPC, MD simulation, measurement of cytokines activity
  
   
  
  Bacteroides vulgatus mpk
  CSDB ID 3349 (all data & tools)
• Article ID: 6108
  Marchetti R, Forgione RE, Fabregat FN, Di Carluccio C, Molinaro A, Silipo A "Solving the structural puzzle of bacterial glycome" - Current Opinion in Structural Biology 68 (2021) 74-83
  

  The analysis of the bacterial glycome (glycomics) is among the complex 'omics' analysis owing to the inherent difficulties in structural and functional characterization of glycans. The complexity and variability of bacterial glycans, spanning from simple carbohydrates to complex glycolipids, glycopeptides and glycoproteins, make their study a challenging research area. The last two decades have witnessed tremendous advances and development of highly sophisticated methods, in combination with optimized protocols and hyphenate techniques for the understanding of structure, conformations, dynamics and organization of microbial glycans. We here present an overview of the novel approaches that have massively improved our understanding of the carbohydrate-based world of bacteria.

  Bacterial, characterization, glycopolymer, Glycomics, glycome, microbial glycans

  NCBI PubMed ID: 33434849
  Publication DOI: 10.1016/j.sbi.2020.12.003
  Journal NLM ID: 9107784
  Publisher: Elsevier
  Correspondence: silipo@unina.it
  Institutions: Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Universita di Napoli Federico II, Via Cintia 4, I-80126 Napoli, Italy
  
   
  
  Bacteroides vulgatus
  CSDB ID 10904 (all data & tools)

Show legend Show as text

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

• 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
  
   
  
  Bacteroides vulgatus mpk
  CSDB ID 7941 (all data & tools)

Show legend Show as text

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

• Article ID: 6232
  Garcia-Vello P, Di Lorenzo F, Zucchetta D, Zamyatina A, De Castro C, Molinaro A "Lipopolysaccharide lipid A: A promising molecule for new immunity-based therapies and antibiotics" - Pharmacology and Therapeutics 230 (2022) 107970
  

  Lipopolysaccharides (LPS) are the main components of the external leaflet of the Gram-negative outer membrane and consist of three different moieties: lipid A, core oligosaccharide, and O-polysaccharide. The lipid A is a glucosamine disaccharide with different levels of acylation and phosphorylation, beside carrying, in certain cases, additional substituents on the sugar backbone. It is also the main immunostimulatory part of the LPS, as its recognition by the host immune system represents a fundamental event for detection of perilous microorganisms. Moreover, an uncontrolled immune response caused by a large amount of circulating LPS can lead to dramatic outcomes for human health, such as septic shock. The immunostimulant properties of an LPS incredibly vary depending on lipid A chemical structure, and for this reason, natural and synthetic variants of the lipid A are under study to develop new drugs that mimic or antagonise its natural effects. Here, we review past and recent findings on the lipid A as an antibiotic target and immune-therapeutic molecule, with a special attention on the crucial role of the chemical structure and its exploitation for conceiving novel strategies for treatment of several immune-related pathologies.

  Lipopolysaccharide, lipid A, inflammation, immune system, adjuvant

  NCBI PubMed ID: 34454000
  Publication DOI: 10.1016/j.pharmthera.2021.107970
  Journal NLM ID: 7905840
  Publisher: Oxford, Elmsford, NY: Pergamon Press
  Correspondence: P. Garcia-Vello ; A. Molinaro
  Institutions: Department of Chemical Sciences, University of Naples Federico II, Napoli, Italy, Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
  
   
  
  Bacteroides vulgatus
  CSDB ID 20947 (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
  
   
  
  Bacteroides vulgatus
  CSDB ID 22389 (all data & tools)