Show legend Show as text

Structure type: oligomer
Trivial name: core-lipid A carbohydrate backbone, epitope G
Compound class: core oligosaccharide, LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_141807,IEDB_150760,IEDB_150908,IEDB_151531

• Article ID: 806
  Heine H, Müller-Loennies S, Brade L, Lindner B, Brade H "Endotoxic activity and chemical structure of lipopolysaccharides from Chlamydia trachomatis serotypes E and L2 and Chlamydophila psittaci 6BC" - European Journal of Biochemistry 270(3) (2003) 440-450
  

  The lipopolysaccharide (LPS) of Chlamydia trachomatis serotype E was isolated from tissue culture-grown elementary bodies and analyzed structurally by mass spectrometry and 1H, 13C and 31P nuclear magnetic resonance. The LPS is composed of the same pentasaccharide bisphosphate αKdo-(2-8)-αKdo-(2-4)-αKdo-(2-6)-βGlcN-4P-(1-6) αGlcN-1P (Kdo is 3-deoxy-α-D-manno-oct-2-ulosonic acid) as reported for C. trachomatis serotype L2[Rund, S., Lindner, B., Brade, H. and Holst, O. (1999) J. Biol. Chem. 274, 16819-16824]. The glucosamine disaccharide backbone is substituted with a complex mixture of fatty acids with ester or amide linkage whereby no ester-linked hydroxy fatty acids were found. The LPS was purified carefully (with contaminations by protein or nucleic acids below 0.3%) and tested for its ability to induce proinflammatory cytokines in several readout systems in comparison to LPS from C. trachomatis serotype L2 and Chlamydophila psittaci strain 6BC as well as enterobacterial smooth and rough LPS and synthetic hexaacyl lipid A. The chlamydial LPS were at least 10 times less active than typical endotoxins; specificity of the activities was confirmed by inhibition with the LPS antagonist, B1233, or with monoclonal antibodies against chlamydial LPS. Like other LPS, the chlamydial LPS used toll-like receptor TLR4 for signalling, but unlike other LPS activation was strictly CD14-dependent.

  LPS, Chlamydia, Chlamydia trachomatis, Chlamydophila psittaci, MALDI-TOF MS, toll-like receptors, innate immunity, ESI-FTIR-MS, ESI-FT-IR MS

  NCBI PubMed ID: 12542694
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: hbrade@fz-borstel.de
  Institutions: Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany
  Methods: HPAEC
  
   
  
  Chlamydia trachomatis E
  CSDB ID 2405 (all data & tools)
• Article ID: 814
  Holst O, Bock K, Brade L, Brade H "The structures of oligosaccharide bisphosphates isolated from the lipopolysaccharide of a recombinant Escherichia coli strain expressing the gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] of Chlamydia psittaci 6BC" - European Journal of Biochemistry 229 (1995) 194-200
  

  The lipopolysaccharide from the recombinant strain Escherichia coli F515-140 containing the cloned gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] from Chlamydia psittaci 6BC was isolated and sequentially de-O-acylated and de-N-acylated. The products were separated by high-performance anion-exchange chromatography into three fractions, two of which contained a single compound. Their structures were elucidated by high-field NMR spectroscopy as α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 1) (tetrasaccharide bisphosphate) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710] and α-Kdo-(2→4)-[α-Kdo-(2→8)-]-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 4) (hexasaccharide bisphosphate). The third fraction comprised two pentasaccharide bisphosphates, which could be separated by affinity chromatography using an immobilized monoclonal antibody specific for the trisaccharide α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo. The bound fraction was identified as α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 2) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710], whereas the unbound fraction was identified as α-Kdo-(2→4)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 3). This novel Kdo tetrasaccharide extends our knowledge on multifunctional Kdo transferases.

  Lipopolysaccharide, LPS, oligosaccharide, structure, core, gene, strain, Escherichia, Escherichia coli, acid, Kdo, transferase, phosphate, Chlamydia, recombinant, bisphosphate, Chlamydia psittaci, gseA, HPLC

  NCBI PubMed ID: 7744029
  Publication DOI: 10.1111/j.1432-1033.1995.0194l.x
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: oholst@fz-borstel.de
  Institutions: Division of Biochemical Microbiology, Forschungsinstitut Borstel, Germany, Division of Biochemical Microbiology, Institut fur Experimentelle Biologie und Medizin, Forschungsinstitut Borstel, Germany, Department of Chemistry, Carisberg Laboratory, Copenhagen, Denmark
  Methods: 13C NMR, 1H NMR, GLC-MS, 31P NMR, HPAEC, affinity chromatography
  
   
  
  Escherichia coli F515-140
  CSDB ID 2501 (all data & tools)
• Article ID: 1156
  Rund S, Lindner B, Brade H, Holst O "Structural analysis of the lipopolysaccharide from Chlamydia trachomatis serotype L2" - Journal of Biological Chemistry 274(24) (1999) 16819-16824
  

  The lipopolysaccharide (LPS) of Chlamydia trachomatis L2 was isolated from tissue culture-grown elementary bodies using a modified phenol/water procedure followed by extraction with phenol/chloroform/light petroleum. From a total of 5 x 10(4) cm2 of infected monolayers, 22.3 mg of LPS were obtained. Compositional analysis indicated the presence of 3-deoxy-D-manno-oct-2-ulopyranosonic acid (Kdo), GlcN, phosphorus, and fatty acids in a molar ratio of 2.8:2:2.1:4.5. Matrix-assisted laser-desorption ionization mass spectrometry performed on the de-O-acylated LPS gave a major molecular ion peak at m/z 1781.1 corresponding to a molecule of 3 Kdo, 2 GlcN, 2 phosphates, and two 3-hydroxyeicosanoic acid residues. The structure of deacylated LPS obtained after successive treatment with hydrazine and potassium hydroxide was determined by 600 MHz NMR spectroscopy as Kdo α2→8 Kdo α2→4 Kdo α2→6 DGlcpN β1→6 DGlcpNα 1,4'-bisphosphate. These data, together with those published recently on the acylation pattern of chlamydial lipid A (Qureshi, N., Kaltashov, I., Walker, K., Doroshenko, V., Cotter, R. J., Takayama, K, Sievert, T. R., Rice, P. A., Lin, J.-S. L., and Golenbock, D. T. (1997) J. Biol. Chem. 272, 10594-10600) allow us to present for the first time the complete structure of a major molecular species of a chlamydial LPS

  Lipopolysaccharide, structural, serotype, analysis, structural analysis, Chlamydia, Chlamydia trachomatis

  NCBI PubMed ID: 10358025
  Publication DOI: 10.1074/jbc.274.24.16819
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: hbrade@fz-borstel.de
  Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Center for Medicine and Biosciences, D-23845 Borstel, Germany
  Methods: 13C NMR, 1H NMR, NMR-2D, MALDI-MS
  
   
  
  Chlamydia trachomatis L2
  CSDB ID 4382 (all data & tools)
• Article ID: 1157
  Rund S, Lindner B, Brade H, Holst O "Structural analysis of the lipopolysaccharide from Chlamydophila psittaci strain 6BC" - European Journal of Biochemistry 267(18) (2000) 5717-5726
  

  The lipopolysaccaride of Chlamydophila psittaci 6BC was isolated from tissue culture-grown elementary bodies using a modified phenol/water procedure followed by extraction with phenol/chloroform/light petroleum. Compositional analyses indicated the presence of 3-deoxy-Dmanno-oct-2-ulosonic acid, GlcN, organic bound phosphate and fatty acids in a molar ratio of approximately 3. 3 : 2 : 1.8 : 4.6. Deacylated lipopolysaccharide was obtained after successive microscale treatment with hydrazine and potassium hydroxide, and was then separated by high performance anion-exchange chromatography into two major fractions, the structures of which were determined by 600 MHz NMR spectroscopy as α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcpN-(1→6)-α-D-GlcpN 1,4'-bisphosphate and α-Kdo-(2→4)-[α-Kdo-(2→8)]-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcpN-(1→6)-α-D-GlcpN 1,4'-bisphosphate. The distribution of fatty acids in lipid A was determined by compositional analyses andmatrix-assisted laser desorption/ionization time-of-flight mass spectrometry experiments on lipid A and de-O-acylated lipid A. It was shown that the carbohydrate backbone of lipid A is replaced by a complex mixture of fatty acids, including long-chain and branched (R)-configured 3-hydroxy fatty acids, the latter being exclusively present in an amide linkage

  Lipopolysaccharide, strain, structural, serotype, analysis, structural analysis, Chlamydophila psittaci, NMR spectroscopy, mass spectrometry

  NCBI PubMed ID: 10971582
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: oholst@fz-borstel.de
  Institutions: Divisions of Medical and Biochemical Microbiology and Biophysics, Research Center Borstel, Center for Medicine and Biosciences, Germany
  Methods: 13C NMR, 1H NMR, NMR-2D, MALDI-TOF MS
  
   
  
  Chlamydophila psittaci 6BC
  CSDB ID 4383 (all data & tools)
• Article ID: 1386
  Brabetz W, Lindner B, Brade H "Comparative analyses of secondary gene products of 3-deoxy-D-manno-oct-2-ulosonic acid transferases from Chlamydiaceae in Escherichia coli K-12" - European Journal of Biochemistry 267(17) (2000) 5458-5465
  

  The waaA gene encoding the essential, lipopolysaccharide (LPS)-specific 3-deoxy-Dmanno-oct-2-ulosonic acid (Kdo) transferase was inactivated in the chromosome of a heptosyltransferase I and II deficient Escherichia coli K-12 strain by insertion of gene expression cassettes encoding the waaA genes of Chlamydia trachomatis, Chlamydophila pneumoniae or Chlamydophila psittaci. The three chlamydial Kdo transferases were able to complement the knockout mutation without changing the growth or multiplication behaviour. The LPS of the mutants were serologically and structurally characterized in comparison to the LPS of the parent strain using compositional analyses, high performance anion exchange chromatography, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and specific monoclonal antibodies. The data show that chlamydial Kdo transferases can replace in E. coli K-12 the host's Kdo transferase and retain the product specificities described in their natural background. In addition, we unequivocally proved that WaaA from C. psittaci transfers predominantly four Kdo residues to lipid A, forming a branched tetrasaccharide with the structure α-Kdo-(2→8)-[α-Kdo-(2→4)]-α-Kdo-(2→4)-α-Kdo.

  Lipopolysaccharide, LPS, gene, Escherichia, Escherichia coli, 3-deoxy-D-manno-oct-2-ulosonic acid, acid, Kdo, transferase, transferases, Chlamydiaceae, genetic complementation, multifunctional 3-deoxy-D-manno-oct-2, product specificity, ulosonic acid transferases

  NCBI PubMed ID: 10951204
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: wbrabetz@fz-borstel.de
  Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany, Divizion of Medical and Biochemical Microbiology, Research Centre Borstel, Centre for Medicine and Biosciences,Borstel,Germany
  
   
  
  Chlamydia trachomatis L2, Chlamydophila pneumoniae TW-183, Chlamydophila psittaci 6BC, Escherichia coli K12 (WBB51), Escherichia coli K12 (WBB52), Escherichia coli K12 (WBB53)
  CSDB ID 6418 (all data & tools)
• Article ID: 2446
  Holst O, Broer W, Thomas-Oates JE, Mamat U, Brade H "Structural analysis of two oligosaccharide biphosphates isolated from the lipopolysaccharide of a recombinant strain of Escherichia coli F515 (Re chemotype) expressing the genus-specific epitope of Chlamydia lipopolysaccharide" - European Journal of Biochemistry 214(3) (1993) 703-710
  

  The lipopolysaccharide of the recombinant strain Escherichia coli F515-207, expressing the genus-specific epitope of Chlamydia lipopolysaccharide, was sequentially de-O- and de-N-acylated by mild hydrazinolysis and treatment with 4 M KOH, respectively, yielding two oligosaccharide bisphosphates which were isolated by high-performance anion-exchange chromatography and gel-permeation chromatography. Their structures were determined by chemical analysis, NMR spectroscopy, and mass spectrometry as α-Kdo-(2-4)-α-Kdo-(2-6)-β-D-GlcN-(1-6)-α-D-GlcN 1,4'-P2 (tetrasaccharide bisphosphate) and α-Kdo-(2-8)-α-Kdo-(2-4)-α-Kdo-(2-6)-β-D-GlcN-(1-6)-α- D-GlcN 1,4'-P2 (pentasaccharide bisphosphate).

  NCBI PubMed ID: 7686488
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Institutions: Division of Biochemical Microbiology, Forschungsinstitut Borstel, Germany
  
   
  
  Escherichia coli F515-207
  CSDB ID 124181 (all data & tools)
• Article ID: 3825
  Brooks CL, Müller-Loennies S, Borisova SN, Brade L, Kosma P, Hirama T, MacKenzie CR, Brade H, Evans SV "Antibodies raised against chlamydial lipopolysaccharide antigens reveal convergence in germline gene usage and differential epitope recognition" - Biochemistry 49(3) (2010) 570-581
  

  The structures of antigen-binding fragments from two related monoclonal antibodies have been determined to high resolution in the presence of several carbohydrate antigens raised against chlamydial lipopolysaccharide. With the exception of CDR H3, antibodies S54-10 and S73-2 are both derived from the same set of germline gene segments as the previously reported structures S25-2 and S45-18. Despite this similarity, the antibodies differ in specificity and the mechanism by which they recognize their cognate antigen. S54-10 uses an unrelated CDR H3 to recognize its antigen in a fashion analogous to S45-18; however, S73-2 recognizes the same antigen as S45-18 and S54-10 in a wholly unrelated manner. Together, these antibody-antigen structures provide snapshots into how the immune system uses the same set of inherited germline gene segments to generate multiple possible specificities that allow for differential recognition of epitopes and how unrelated CDR H3 sequences can result in convergent binding of clinically relevant bacterial antigens.

  antibodies, epitope, recognition, antigens, Chlamydia, binding

  NCBI PubMed ID: 20000757
  Journal NLM ID: 0370623
  Publisher: American Chemical Society
  Correspondence: hebra@fz-borstel.de; svevans@uvic.ca
  Institutions: University of Victoria, Department of Biochemistry and Microbiology, PO Box 3055 STN CSC, Victoria, BC, Canada V8P 3P6
  Methods: ELISA, serological methods, genetic methods, crystallization, surface plasmon resonance (SPR)
  
   
  
  Chlamydia
  CSDB ID 25194 (all data & tools)
• Article ID: 4485
  Brooks CL, Wimmer K, Kosma P, Müller-Loennies S, Brade L, Brade H, Evans SV "Exploring the cross-reactivity of S25-2: complex with a 5,6-dehydro-Kdo disaccharide" - Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 69(1) (2013) 2-5
  

  The near-germline antibody S25-2 exhibits a remarkable cross-reactivity for oligosaccharides containing the bacterial lipopolysaccharide carbohydrate 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo). The recent synthesis of a variety of Kdo analogues permits a detailed structural analysis of the importance of specific interactions in antigen recognition by S25-2. The Kdo disaccharide analogue Kdo-(2→4)-5,6-dehydro-Kdo lacks a 5-OH group on the second Kdo residue and has been cocrystallized with S25-2. The structure reveals that the modification of the Kdo residue at position 5 results in a rearrangement of intramolecular hydrogen bonds in the antigen that allows it to assume a novel conformation in the antibody-combining site. The cross-reactive binding of S25-2 to this synthetic ligand highlights the adaptability of this antibody to non-natural synthetic analogues.

  5, 6-dehydro-Kdo disaccharide, 4hgw, antibody S25-2

  NCBI PubMed ID: 23295476
  Publication DOI: 10.1107/S1744309112047422
  Journal NLM ID: 101226117
  Publisher: Oxford, England: Wiley-Blackwell
  Correspondence: cbrooks1@ualberta.ca; svevans@uvic.ca
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC V8W 3P6, Canada
  Methods: crystallization
  
   
  
  Chlamydia
  CSDB ID 29922 (all data & tools)

Show legend Show as text

Structure type: oligomer
Trivial name: core-lipid A backbone, epitope J
Compound class: core oligosaccharide, LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_140092,IEDB_141807,IEDB_150755,IEDB_150756,IEDB_150760,IEDB_150901,IEDB_150908,IEDB_151531,IEDB_151769

• Article ID: 814
  Holst O, Bock K, Brade L, Brade H "The structures of oligosaccharide bisphosphates isolated from the lipopolysaccharide of a recombinant Escherichia coli strain expressing the gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] of Chlamydia psittaci 6BC" - European Journal of Biochemistry 229 (1995) 194-200
  

  The lipopolysaccharide from the recombinant strain Escherichia coli F515-140 containing the cloned gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] from Chlamydia psittaci 6BC was isolated and sequentially de-O-acylated and de-N-acylated. The products were separated by high-performance anion-exchange chromatography into three fractions, two of which contained a single compound. Their structures were elucidated by high-field NMR spectroscopy as α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 1) (tetrasaccharide bisphosphate) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710] and α-Kdo-(2→4)-[α-Kdo-(2→8)-]-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 4) (hexasaccharide bisphosphate). The third fraction comprised two pentasaccharide bisphosphates, which could be separated by affinity chromatography using an immobilized monoclonal antibody specific for the trisaccharide α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo. The bound fraction was identified as α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 2) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710], whereas the unbound fraction was identified as α-Kdo-(2→4)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcN-(1→6)-α-D-GlcN 1,4'-P2 (compound 3). This novel Kdo tetrasaccharide extends our knowledge on multifunctional Kdo transferases.

  Lipopolysaccharide, LPS, oligosaccharide, structure, core, gene, strain, Escherichia, Escherichia coli, acid, Kdo, transferase, phosphate, Chlamydia, recombinant, bisphosphate, Chlamydia psittaci, gseA, HPLC

  NCBI PubMed ID: 7744029
  Publication DOI: 10.1111/j.1432-1033.1995.0194l.x
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: oholst@fz-borstel.de
  Institutions: Division of Biochemical Microbiology, Forschungsinstitut Borstel, Germany, Division of Biochemical Microbiology, Institut fur Experimentelle Biologie und Medizin, Forschungsinstitut Borstel, Germany, Department of Chemistry, Carisberg Laboratory, Copenhagen, Denmark
  Methods: 13C NMR, 1H NMR, GLC-MS, 31P NMR, HPAEC, affinity chromatography
  
   
  
  Escherichia coli F515-140
  CSDB ID 2503 (all data & tools)
• Article ID: 1157
  Rund S, Lindner B, Brade H, Holst O "Structural analysis of the lipopolysaccharide from Chlamydophila psittaci strain 6BC" - European Journal of Biochemistry 267(18) (2000) 5717-5726
  

  The lipopolysaccaride of Chlamydophila psittaci 6BC was isolated from tissue culture-grown elementary bodies using a modified phenol/water procedure followed by extraction with phenol/chloroform/light petroleum. Compositional analyses indicated the presence of 3-deoxy-Dmanno-oct-2-ulosonic acid, GlcN, organic bound phosphate and fatty acids in a molar ratio of approximately 3. 3 : 2 : 1.8 : 4.6. Deacylated lipopolysaccharide was obtained after successive microscale treatment with hydrazine and potassium hydroxide, and was then separated by high performance anion-exchange chromatography into two major fractions, the structures of which were determined by 600 MHz NMR spectroscopy as α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcpN-(1→6)-α-D-GlcpN 1,4'-bisphosphate and α-Kdo-(2→4)-[α-Kdo-(2→8)]-α-Kdo-(2→4)-α-Kdo-(2→6)-β-D-GlcpN-(1→6)-α-D-GlcpN 1,4'-bisphosphate. The distribution of fatty acids in lipid A was determined by compositional analyses andmatrix-assisted laser desorption/ionization time-of-flight mass spectrometry experiments on lipid A and de-O-acylated lipid A. It was shown that the carbohydrate backbone of lipid A is replaced by a complex mixture of fatty acids, including long-chain and branched (R)-configured 3-hydroxy fatty acids, the latter being exclusively present in an amide linkage

  Lipopolysaccharide, strain, structural, serotype, analysis, structural analysis, Chlamydophila psittaci, NMR spectroscopy, mass spectrometry

  NCBI PubMed ID: 10971582
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: oholst@fz-borstel.de
  Institutions: Divisions of Medical and Biochemical Microbiology and Biophysics, Research Center Borstel, Center for Medicine and Biosciences, Germany
  Methods: 13C NMR, 1H NMR, NMR-2D, MALDI-TOF MS
  
   
  
  Chlamydophila psittaci 6BC
  CSDB ID 4460 (all data & tools)
• Article ID: 1386
  Brabetz W, Lindner B, Brade H "Comparative analyses of secondary gene products of 3-deoxy-D-manno-oct-2-ulosonic acid transferases from Chlamydiaceae in Escherichia coli K-12" - European Journal of Biochemistry 267(17) (2000) 5458-5465
  

  The waaA gene encoding the essential, lipopolysaccharide (LPS)-specific 3-deoxy-Dmanno-oct-2-ulosonic acid (Kdo) transferase was inactivated in the chromosome of a heptosyltransferase I and II deficient Escherichia coli K-12 strain by insertion of gene expression cassettes encoding the waaA genes of Chlamydia trachomatis, Chlamydophila pneumoniae or Chlamydophila psittaci. The three chlamydial Kdo transferases were able to complement the knockout mutation without changing the growth or multiplication behaviour. The LPS of the mutants were serologically and structurally characterized in comparison to the LPS of the parent strain using compositional analyses, high performance anion exchange chromatography, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and specific monoclonal antibodies. The data show that chlamydial Kdo transferases can replace in E. coli K-12 the host's Kdo transferase and retain the product specificities described in their natural background. In addition, we unequivocally proved that WaaA from C. psittaci transfers predominantly four Kdo residues to lipid A, forming a branched tetrasaccharide with the structure α-Kdo-(2→8)-[α-Kdo-(2→4)]-α-Kdo-(2→4)-α-Kdo.

  Lipopolysaccharide, LPS, gene, Escherichia, Escherichia coli, 3-deoxy-D-manno-oct-2-ulosonic acid, acid, Kdo, transferase, transferases, Chlamydiaceae, genetic complementation, multifunctional 3-deoxy-D-manno-oct-2, product specificity, ulosonic acid transferases

  NCBI PubMed ID: 10951204
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Correspondence: wbrabetz@fz-borstel.de
  Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany, Divizion of Medical and Biochemical Microbiology, Research Centre Borstel, Centre for Medicine and Biosciences,Borstel,Germany
  
   
  
  Chlamydophila psittaci 6BC, Escherichia coli K12 (WBB52)
  CSDB ID 6287 (all data & tools)
• Article ID: 3825
  Brooks CL, Müller-Loennies S, Borisova SN, Brade L, Kosma P, Hirama T, MacKenzie CR, Brade H, Evans SV "Antibodies raised against chlamydial lipopolysaccharide antigens reveal convergence in germline gene usage and differential epitope recognition" - Biochemistry 49(3) (2010) 570-581
  

  The structures of antigen-binding fragments from two related monoclonal antibodies have been determined to high resolution in the presence of several carbohydrate antigens raised against chlamydial lipopolysaccharide. With the exception of CDR H3, antibodies S54-10 and S73-2 are both derived from the same set of germline gene segments as the previously reported structures S25-2 and S45-18. Despite this similarity, the antibodies differ in specificity and the mechanism by which they recognize their cognate antigen. S54-10 uses an unrelated CDR H3 to recognize its antigen in a fashion analogous to S45-18; however, S73-2 recognizes the same antigen as S45-18 and S54-10 in a wholly unrelated manner. Together, these antibody-antigen structures provide snapshots into how the immune system uses the same set of inherited germline gene segments to generate multiple possible specificities that allow for differential recognition of epitopes and how unrelated CDR H3 sequences can result in convergent binding of clinically relevant bacterial antigens.

  antibodies, epitope, recognition, antigens, Chlamydia, binding

  NCBI PubMed ID: 20000757
  Journal NLM ID: 0370623
  Publisher: American Chemical Society
  Correspondence: hebra@fz-borstel.de; svevans@uvic.ca
  Institutions: University of Victoria, Department of Biochemistry and Microbiology, PO Box 3055 STN CSC, Victoria, BC, Canada V8P 3P6
  Methods: ELISA, serological methods, genetic methods, crystallization, surface plasmon resonance (SPR)
  
   
  
  Chlamydia psittaci
  CSDB ID 25551 (all data & tools)

Show legend Show as text

Structure type: oligomer
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_135813,IEDB_137340,IEDB_141807,IEDB_150077,IEDB_150760,IEDB_150908,IEDB_151531,IEDB_151767,IEDB_156486,IEDB_164045

• Article ID: 1103
  Peterson EM, de la Maza L, Brade L, Brade H "Characterization of a neutralizing monoclonal antibody directed at the lipopolysaccharide of Chlamydia pneumoniae" - Infection and Immunity 66(8) (1998) 3848-3855
  

  Identification of protective epitopes is one of the first steps in the development of a subunit vaccine. One approach to accomplishing this is to identify structures or epitopes by using monoclonal antibodies (MAb) that can attenuate infectivity in vitro and in vivo. To date attempts to use this approach with Chlamydia pneumoniae have failed. This report is the first description of a MAb directed to the lipopolysaccharide (LPS) of Chlamydia that neutralizes both in vitro and in vivo the infectivity of C. pneumoniae. MAb CP-33, an immunoglobulin G2b (IgG2b), was identified from a fusion using splenocytes from mice immunized with C. pneumoniae TW-183. By Western blot analysis, MAb CP-33 exhibited genus-specific reactivity in that it recognized the LPSs of C. pneumoniae, Chlamydia trachomatis, and Chlamydia psittaci. MAb CP-33 did not react with 15 genera of gram-negative and gram-positive bacteria and Candida albicans. By using isolated LPS of Re mutants of Escherichia coli, Salmonella enterica serovar Minnesota, and recombinants expressing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase gene kdtA of C. trachomatis, MAb CP-33 was shown to require for binding the presence of the genus-specific trisaccharide epitope αKdo(2→8)αKdo(2→4)αKdo. By employing synthetic oligosaccharides and neoglycoconjugates in an enzyme immunoassay (EIA) and EIA inhibition, it was further shown that MAb CP-33 differed from the extensively investigated prototype chlamydial LPS MAb S25-23. Most likely, MAb CP-33 recognizes a conformational epitope in which the αKdo(2→8)αKdo(2→4)αKdo trisaccharide is an essential structural component. When tested in an in vitro neutralization assay, MAb CP-33 gave a 50% neutralization titer of 8 ng/ml against C. pneumoniae TW-183. However, this MAb did not neutralize other C. pneumoniae strains, C. trachomatis, or C. psittaci. C. pneumoniae TW-183 was treated with either MAb CP-33 or a control IgG and then used to inoculate mice by the respiratory route. Five days after inoculation, there was a difference between the mice inoculated with the control IgG-treated inoculum and those inoculated with the MAb CP-33-treated organisms as to the number of mice infected as well as the number of inclusion-forming units recovered from lung cultures (P < 0.05). In summary, a Chlamydia-specific LPS MAb was able to neutralize in vitro the infectivity of C. pneumoniae TW-183.

  Lipopolysaccharide, core, characterization, antibodies, antibody, epitope, monoclonal, monoclonal antibodies, monoclonal antibody, Chlamydia, protective, neutralizing

  NCBI PubMed ID: 9673271
  Journal NLM ID: 0246127
  Publisher: American Society for Microbiology
  Correspondence: epeterso@uci.edu
  Institutions: Department of Pathology, University of California, Irvine , Ervine, California 92697-4800, Forschungsinstitut Borstel, Zentrum fur Medizin und Biowiddenschaften, Medizinische und Biochemische Mikrobiologie, 23845 Borstel, Germany
  Methods: serological methods
  
   
  
  Chlamydia pneumoniae F515-207
  CSDB ID 4148 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_141807,IEDB_150760,IEDB_150908,IEDB_151531

• Article ID: 1156
  Rund S, Lindner B, Brade H, Holst O "Structural analysis of the lipopolysaccharide from Chlamydia trachomatis serotype L2" - Journal of Biological Chemistry 274(24) (1999) 16819-16824
  

  The lipopolysaccharide (LPS) of Chlamydia trachomatis L2 was isolated from tissue culture-grown elementary bodies using a modified phenol/water procedure followed by extraction with phenol/chloroform/light petroleum. From a total of 5 x 10(4) cm2 of infected monolayers, 22.3 mg of LPS were obtained. Compositional analysis indicated the presence of 3-deoxy-D-manno-oct-2-ulopyranosonic acid (Kdo), GlcN, phosphorus, and fatty acids in a molar ratio of 2.8:2:2.1:4.5. Matrix-assisted laser-desorption ionization mass spectrometry performed on the de-O-acylated LPS gave a major molecular ion peak at m/z 1781.1 corresponding to a molecule of 3 Kdo, 2 GlcN, 2 phosphates, and two 3-hydroxyeicosanoic acid residues. The structure of deacylated LPS obtained after successive treatment with hydrazine and potassium hydroxide was determined by 600 MHz NMR spectroscopy as Kdo α2→8 Kdo α2→4 Kdo α2→6 DGlcpN β1→6 DGlcpNα 1,4'-bisphosphate. These data, together with those published recently on the acylation pattern of chlamydial lipid A (Qureshi, N., Kaltashov, I., Walker, K., Doroshenko, V., Cotter, R. J., Takayama, K, Sievert, T. R., Rice, P. A., Lin, J.-S. L., and Golenbock, D. T. (1997) J. Biol. Chem. 272, 10594-10600) allow us to present for the first time the complete structure of a major molecular species of a chlamydial LPS

  Lipopolysaccharide, structural, serotype, analysis, structural analysis, Chlamydia, Chlamydia trachomatis

  NCBI PubMed ID: 10358025
  Publication DOI: 10.1074/jbc.274.24.16819
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: hbrade@fz-borstel.de
  Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Center for Medicine and Biosciences, D-23845 Borstel, Germany
  Methods: 13C NMR, 1H NMR, NMR-2D, MALDI-MS
  
   
  
  Chlamydia trachomatis L2
  CSDB ID 4474 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: Ethanolamine
Compound class: LOS
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_130670,IEDB_133751,IEDB_135394,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137777,IEDB_137778,IEDB_140088,IEDB_140092,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_150760,IEDB_150901,IEDB_150908,IEDB_151528,IEDB_151531,IEDB_190606,IEDB_2189047,IEDB_226811,IEDB_983931,SB_192,SB_7

• Article ID: 3047
  Helander IM, Kilpeläinen I, Vaara M "Increased substitution of phosphate groups in lipopolysaccharides and lipid A of the polymyxin-resistant pmrA mutants of Salmonella typhimurium: a 31P-NMR study" - Molecular Microbiology 11 (1994) 481-487
  

  De-O-acylated lipopolysaccharides (LPS) of three polymyxin-resistant Salmonella typhimurium pmrA mutants and their parent strains were analysed by 31P-NMR (nuclear magnetic resonance) in order to assess, in relation to polymyxin resistance, the types and degree of substitution of phosphates of the LPS and lipid A. In the pmrA mutant LPS phosphate diesters predominated over phosphate monoesters, whereas the latter were more abundant in the parent wild-type LPS. The increase in the proportion of phosphate diesters was traced to both the core oligosaccharide and the lipid A part. In the latter, the ester-linked phosphate at position 4' was to a large extent (79-88%) substituted with 4-amino-4-deoxy-L-arabinose, whereas in the wild-type LPS the 4'-phosphate was mainly present as monoester. In each LPS, regardless of the pmrA mutation, the glycosidically linked phosphate of lipid A was largely unsubstituted.

  NCBI PubMed ID: 8152372
  Journal NLM ID: 8712028
  Publisher: Blackwell Publishing
  Institutions: Department of Molecular Bacteriology, National Public Health Institute, Helsinki, Finland
  
   
  
  Salmonella typhimurium
  CSDB ID 144077 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: BSA
Trivial name: neoglycoconjugate
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_130662,IEDB_135394,IEDB_135813,IEDB_137340,IEDB_140092,IEDB_141807,IEDB_150077,IEDB_150755,IEDB_150756,IEDB_150760,IEDB_150901,IEDB_150908,IEDB_151531,IEDB_151767,IEDB_151768,IEDB_151769,IEDB_156486,IEDB_156487,IEDB_164045

• Article ID: 3163
  Müller-Loennies S, Gronow S, Brade L, Mackenzie R, Kosma P, Brade H "A monoclonal antibody against a carbohydrate epitope in lipopolysaccharide differentiates Chlamydophila psittaci from Chlamydophila pecorum, Chlamydophila pneumoniae, and Chlamydia trachomatis" - Glycobiology 16(3) (2006) 184-196
  

  Lipopolysaccharide (LPS) of Chlamydophila psittaci but not of Chlamydophila pneumoniae or Chlamydia trachomatis contains a tetrasaccharide of 3-deoxy-α-D-manno-oct-2-ulopyranosonic acid (Kdo) of the sequence Kdo(2→8)[Kdo(2→4)]Kdo(2→4)Kdo. After immunization with the synthetic neoglycoconjugate antigen Kdo(2→8)[Kdo(2→4)]Kdo(2→4) Kdo-BSA, we obtained the mouse monoclonal antibody (mAb) S69-4 which was able to differentiate C. psittaci from Chlamydophila pecorum, C. pneumoniae, and C. trachomatis in double labeling experiments of infected cell monolayers and by enzyme-linked immunosorbent assay (ELISA). The epitope specificity of mAb S69-4 was determined by binding and inhibition assays using bacteria, LPS, and natural or synthetic Kdo oligosaccharides as free ligands or conjugated to BSA. The mAb bound preferentially Kdo(2→8)[Kdo(2→4)]Kdo(2→4)Kdo(2→4) with a K(d) of 10 microM, as determined by surface plasmon resonance (SPR) for the monovalent interaction using mAb or single chain Fv. Cross-reactivity was observed with Kdo(2→4)Kdo(2→4)Kdo but not with Kdo(2→8)Kdo(2→4)Kdo, Kdo disaccharides in 2→4- or 2→8-linkage, or Kdo monosaccharide. MAb S69-4 was able to detect LPS on thin-layer chromatography (TLC) plates in amounts of <10 ng by immunostaining. Due to the high sensitivity achieved in this assay, the antibody also detected in vitro products of cloned Kdo transferases of Chlamydia. The antibody can therefore be used in medical and veterinarian diagnostics, general microbiology, analytical biochemistry, and studies of chlamydial LPS biosynthesis. Further contribution to the general understanding of carbohydrate-binding antibodies was obtained by a comparison of the primary structure of mAb S69-4 to that of mAb S45-18 of which the crystal structure in complex with its ligand has been elucidated recently (Nguyen et al., 2003, Nat. Struct. Biol., 10, 1019-1025).

  Kdo, diagnostic, neoglycoconjugate, immunofluorescence

  NCBI PubMed ID: 16282606
  Publication DOI: 10.1093/glycob/cwj055
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Correspondence: hebra@fz-borstel.de
  Institutions: Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany, Institute for Biological Sci-ences, National Research Council Canada, Ottawa, Ontario, Canada K1A 0R6, Department of Chemistry, University of Natural Resources and Applied Life Sciences, A-1190 Vienna, Austri
  Methods: serological methods, genetic methods
  
   
  
  Escherichia coli, Chlamydophila psittaci
  CSDB ID 20498 (all data & tools)

Show legend Show as text

Structure type: oligomer
Compound class: LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_141807,IEDB_150760,IEDB_150908,IEDB_151531,IEDB_176772,IEDB_534865

• Article ID: 3851
  Gronow S, Xia G, Brade H "Glycosyltransferases involved in the biosynthesis of the inner core region of different lipopolysaccharides" - European Journal of Cell Biology 89(1) (2010) 3-10
  

  The inner core of lipopolysaccharide (LPS) structures in Gram-negative bacteria is considered a highly conserved region. The sugar connecting the membrane-associated lipid A moiety with the hydrophilic saccharide moiety, 3-deoxy-α-D-manno-oct-2-ulosonic acid (Kdo) is present in every LPS molecule investigated but it may be partially replaced by d-glycero-α-D-talo-oct-2-ulosonic acid (Ko). l-Glycero-α-D-manno-heptose (Hep) and phosphate residues are part of most but not all LPS structures and additionally, modifications with 4-amino-4-deoxy-β-L-arabinose (Ara4N) residues occur in some. A number of different glycosyltransferases is involved in the biosynthesis of the inner core region of different lipopolysaccharides. Here, we report the characterization of Kdo transferases, heptosyltransferases and Ara4N transferases from a variety of bacteria

  Lipopolysaccharide, glycosyltransferases

  NCBI PubMed ID: 19900730
  Journal NLM ID: 7906240
  Institutions: Division of Medical and Biochemical Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany
  
   
  
  Chlamydia trachomatis L2
  CSDB ID 25262 (all data & tools)

Show legend Show as text

Structure type: oligomer
Trivial name: cross-reactive epitope
Compound class: core oligosaccharide, LPS
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_140092,IEDB_141807,IEDB_150755,IEDB_150756,IEDB_150760,IEDB_150901,IEDB_150908,IEDB_151531,IEDB_151769,IEDB_176772,IEDB_534865

• Article ID: 4014
  Evans DW, Müller-Loennies S, Brooks CL, Brade L, Kosma P, Brade H, Evans SV "Structural insights into parallel strategies for germline antibody recognition of lipopolysaccharide from Chlamydia" - Glycobiology 21(8) (2011) 1049-1059
  

  The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 A resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V gene segments that binds the terminal Kdo residue of the antigen; however, although S64-4 shares the same heavy chain V gene segment as S25-2, it has a different light chain V gene segment. The new light chain V gene segment codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use complementarity determining region (CDR) H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene segment and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V gene segments can act as starting points for the generation of germline antibodies against chlamydial antigens and show how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3.

  Chlamydia, crystal structure, carbohydrate antigen, antibody-antigen recognition, chlamydial LPS, germline antibody

  NCBI PubMed ID: 21543444
  Publication DOI: 10.1093/glycob/cwr041
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Correspondence: hebra@fz-borstel.de; svenvans@uvic.ca
  Institutions: Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC, Canada V8P 3P6, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 22, Borstel D-23845, Germany, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna A-1190, Austria
  Methods: X-ray, ELISA, serological methods
  
   
  
  Chlamydia psittaci
  CSDB ID 26190 (all data & tools)
• Article ID: 4677
  Haji-Ghassemi O, Müller-Loennies S, Saldova R, Muniyappa M, Brade L, Rudd PM, Harvey DJ, Kosma P, Brade H, Evans SV "Groove-type recognition of Chlamydiaceae-specific lipopolysaccharide antigen by a family of antibodies possessing an unusual variable heavy chain N-linked glycan" - Journal of Biological Chemistry 289(24) (2014) 16644-16661
  

  The structure of the antigen-binding fragment of mAb S25-26 determined to 1.95 A resolution in complex with the Chlamydiaceae family-specific trisaccharide antigen Kdo(2→8)-Kdo(2→4)Kdo (Kdo=3-deoxy-α-D-manno-oct-2-ulopyranosonic acid) displays a germline-coded paratope that differs significantly from previously characterized Chlamydiaceae-specific mAbs, despite being raised against the identical immunogen. Unlike the terminal Kdo recognition pocket that promotes cross-reactivity in S25-2-type antibodies, S25-26 and the closely related S25-23 utilize a groove composed of germline residues to recognize the entire trisaccharide antigen and so confer strict specificity. Interest in S25-23 was sparked by its rare high muM affinity and strict specificity for the family-specific trisaccharide antigen; however, only the related antibody S25-26 proved amenable to crystallization. The structures of three unliganded forms of S25-26 have a labile complementary determining region H3 adjacent to significant glycosylation of the variable heavy chain on asparagine 85 in Framework Region 3. Analysis of the glycan reveals a heterogeneous mixture with a common root structure that contains an unusually high number of terminal αGal-Gal moieties. One of the few reported structures of glycosylated mAbs containing these epitopes is the therapeutic antibody Cetuximab; however, unlike Cetuximab, one of the unliganded structures in S25-26 shows significant order in the glycan with appropriate electron density for nine residues. The elucidation of the three dimensional structure of an αGal containing N-linked glycan on a mAb variable heavy chain has potential clinical interest, as they have been implicated in allergic response in patients receiving therapeutic antibodies.

  antibodies, epitopes, MAb, Chlamydiaceae, N-linked glycan, lipopolysaccharide antigen

  NCBI PubMed ID: 24682362
  Publication DOI: 10.1074/jbc.M113.528224
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: sml@fz-borstel.de; svevans@uvic.ca
  Institutions: From the Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 3P6, Canada, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 22, Borstel D-23845, Germany
  Methods: X-ray, ELISA, ESI-MS, genetic methods, HPLC, crystallization, ITC
  
   
  
  Chlamydia psittaci 6BC
  CSDB ID 30245 (all data & tools)

Show legend Show as text

Structure type: oligomer
Trivial name: genus-specific epitope
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_130650,IEDB_130657,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_137340,IEDB_141807,IEDB_150760,IEDB_150908,IEDB_151531,IEDB_176772,IEDB_534865

• Article ID: 4077
  Nguyen BD, Cunningham D, Liang X, Chen X, Toone EJ, Raetz CR, Zhou P, Valdivia RH "Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis" - Proceedings of the National Academy of Sciences of the USA 108(25) (2011) 10284-10289
  

  Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase], the enzyme that catalyzes the first committed step in the biosynthesis of lipid A, block the synthesis of LOS in the obligate intracellular bacterial pathogen Chlamydia trachomatis. In the absence of LOS, Chlamydia remains viable and establishes a pathogenic vacuole ('inclusion') that supports robust bacterial replication. However, bacteria grown under these conditions were no longer infectious. In the presence of LpxC inhibitors, replicative reticulate bodies accumulated in enlarged inclusions but failed to express selected late-stage proteins and transition to elementary bodies, a Chlamydia developmental form that is required for invasion of mammalian cells. These findings suggest the presence of an outer membrane quality control system that regulates Chlamydia developmental transition to infectious elementary bodies and highlights the potential application of LpxC inhibitors as unique class of antichlamydial agents.

  Lipooligosaccharide, lipid A, Chlamydia trachomatis, outer membrane

  NCBI PubMed ID: 21628561
  Journal NLM ID: 7505876
  Publisher: National Academy of Sciences
  Correspondence: raetz@biochem.duke.edu
  Institutions: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
  Methods: genetic methods
  
   
  
  Chlamydia trachomatis
  CSDB ID 26295 (all data & tools)