Show legend Show as text

Structure type: fragment of a bigger structure
Trivial name: nonreducing terminal epitope of lipoarabinomannan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 302
  Lee RE, Brennan PJ, Besra GS "Mycobacterium tuberculosis cell envelope" - Book: Tuberculosis (series: Current Topics in Microbiology and Immunology) (1996) Vol. 215, 1-27
  

  The mycobacterial cell wall is a complex and intriguing mixture of components which sets Mycobacterium tuberculosis apart from all other known bacterial species (Goodfellow and Minnikin 1984). To understand the M. tuberculosis cell wall, one must first consider the biology of the tubercle bacillus. Tuberculosis has long been known as a cause of morbidity and mortality worldwide. Indeed it is believed that one third of the word’s population is infected with M. tuberculosis (Sudre et al. 1992). Evidence of tuberculosis-like infections date back many thousands of years, and it is very likely that tuberculosis-related infections have plagued humankind since the dawn of civilization. M. tuberculosis is primarily an intracellular pathogen which resides within the phagolysosomes of alveolar macrophages. Perhaps as a consequence of this intracellular environment, the highly intricate features of the tubercle bacilli cell wall have undergone extensive evolutionary changes.

  lipid, Mycobacteria, membrane, arabinogalactan, cell envelope, lipoarabinomannan, Mycobacterium tuberculosis, peptidoglycan

  Publication DOI: 10.1007/978-3-642-80166-2_1
  Publisher: Berlin, Heidelberg: Springer.
  Editors: Shinnick TM
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, CO, 80523, USA
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 31420 (all data & tools)

Show legend Show as text

Structure type: fragment of a bigger structure
Trivial name: nonreducing terminal epitope of lipoarabinomannan
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_134619,IEDB_136104,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857717,IEDB_857718,IEDB_857722,IEDB_857723,IEDB_857726,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 302
  Lee RE, Brennan PJ, Besra GS "Mycobacterium tuberculosis cell envelope" - Book: Tuberculosis (series: Current Topics in Microbiology and Immunology) (1996) Vol. 215, 1-27
  

  The mycobacterial cell wall is a complex and intriguing mixture of components which sets Mycobacterium tuberculosis apart from all other known bacterial species (Goodfellow and Minnikin 1984). To understand the M. tuberculosis cell wall, one must first consider the biology of the tubercle bacillus. Tuberculosis has long been known as a cause of morbidity and mortality worldwide. Indeed it is believed that one third of the word’s population is infected with M. tuberculosis (Sudre et al. 1992). Evidence of tuberculosis-like infections date back many thousands of years, and it is very likely that tuberculosis-related infections have plagued humankind since the dawn of civilization. M. tuberculosis is primarily an intracellular pathogen which resides within the phagolysosomes of alveolar macrophages. Perhaps as a consequence of this intracellular environment, the highly intricate features of the tubercle bacilli cell wall have undergone extensive evolutionary changes.

  lipid, Mycobacteria, membrane, arabinogalactan, cell envelope, lipoarabinomannan, Mycobacterium tuberculosis, peptidoglycan

  Publication DOI: 10.1007/978-3-642-80166-2_1
  Publisher: Berlin, Heidelberg: Springer.
  Editors: Shinnick TM
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, CO, 80523, USA
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 31422 (all data & tools)

Show legend Show as text

Structure type: fragment of a bigger structure
Trivial name: nonreducing terminal epitope of lipoarabinomannan
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_136104,IEDB_140116,IEDB_141830,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857718,IEDB_857722,IEDB_857726,IEDB_857728,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 302
  Lee RE, Brennan PJ, Besra GS "Mycobacterium tuberculosis cell envelope" - Book: Tuberculosis (series: Current Topics in Microbiology and Immunology) (1996) Vol. 215, 1-27
  

  The mycobacterial cell wall is a complex and intriguing mixture of components which sets Mycobacterium tuberculosis apart from all other known bacterial species (Goodfellow and Minnikin 1984). To understand the M. tuberculosis cell wall, one must first consider the biology of the tubercle bacillus. Tuberculosis has long been known as a cause of morbidity and mortality worldwide. Indeed it is believed that one third of the word’s population is infected with M. tuberculosis (Sudre et al. 1992). Evidence of tuberculosis-like infections date back many thousands of years, and it is very likely that tuberculosis-related infections have plagued humankind since the dawn of civilization. M. tuberculosis is primarily an intracellular pathogen which resides within the phagolysosomes of alveolar macrophages. Perhaps as a consequence of this intracellular environment, the highly intricate features of the tubercle bacilli cell wall have undergone extensive evolutionary changes.

  lipid, Mycobacteria, membrane, arabinogalactan, cell envelope, lipoarabinomannan, Mycobacterium tuberculosis, peptidoglycan

  Publication DOI: 10.1007/978-3-642-80166-2_1
  Publisher: Berlin, Heidelberg: Springer.
  Editors: Shinnick TM
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, CO, 80523, USA
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 31423 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: polymer of -5)aDAraf(1-
Trivial name: lipoarabinomannan
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_134619,IEDB_136104,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857717,IEDB_857718,IEDB_857722,IEDB_857723,IEDB_857726,IEDB_857727,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 742
  Khoo KH, Tang JB, Chatterjee D "Variation in mannose-capped terminal arabinan motifs of lipoarabinomannans from clinical isolates of Mycobacterium tuberculosis and Mycobacterium avium complex" - Journal of Biological Chemistry 276(6) (2001) 3863-3871
  

  The unique terminal arabinan motifs of mycobacterial lipoarabinomannan (LAM), which are mannose-capped to different extents, probably constitute the single most important structural entity engaged in receptor binding and subsequent immunopathogenesis. We have developed a concerted approach of endoarabinanase digestion coupled with chromatography and mass spectrometry analysis to rapidly identify and quantitatively map the complement of such terminal units among the clinical isolates of different virulence and drug resistance profiles. In comparison with LAM from laboratory strains of Mycobacterium tuberculosis, an ethambutol (Emb) resistant clinical isolate was shown to have a significantly higher proportion of nonmannose capped arabinan termini. More drastically, the mannose capping was completely inhibited when an Emb-susceptible strain was grown in the presence of subminimal inhibitory concentration of Emb. Both cases resulted in an increase of arabinose to mannose ratio in the overall glycosyl composition of LAM. Emb, therefore, not only could affect the complete elaboration of the arabinan as found previously for LAM from Mycobacterium smegmatis resistant mutant but also could inhibit the extent of mannose capping and hence its associated biological functions in M. tuberculosis. Unexpectedly, an intrinsically Emb-resistant Mycobacterium avium isolate of smooth transparent colony morphology was found to have most of its arabinan termini capped with a single mannose residue instead of the more common dimannoside as established for LAM from M. tuberculosis. This is the first report on the LAM structure from M. avium complex, an increasingly important opportunistic infectious agent afflicting AIDS patients

  structure, virulence, lipoarabinomannan, Mycobacterium tuberculosis, tuberculosis, Mycobacterium avium Complex

  NCBI PubMed ID: 11073941
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: delphi@lamar.colostate.edu
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA
  Methods: HPAEC, MS, enzymatic digestion
  
   
  
  Mycobacterium tuberculosis CSU19, Mycobacterium avium 2151
  CSDB ID 880 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: polymer of -5)aDAraf(1-
Trivial name: lipoarabinomannan
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_136104,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857718,IEDB_857722,IEDB_857726,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 742
  Khoo KH, Tang JB, Chatterjee D "Variation in mannose-capped terminal arabinan motifs of lipoarabinomannans from clinical isolates of Mycobacterium tuberculosis and Mycobacterium avium complex" - Journal of Biological Chemistry 276(6) (2001) 3863-3871
  

  The unique terminal arabinan motifs of mycobacterial lipoarabinomannan (LAM), which are mannose-capped to different extents, probably constitute the single most important structural entity engaged in receptor binding and subsequent immunopathogenesis. We have developed a concerted approach of endoarabinanase digestion coupled with chromatography and mass spectrometry analysis to rapidly identify and quantitatively map the complement of such terminal units among the clinical isolates of different virulence and drug resistance profiles. In comparison with LAM from laboratory strains of Mycobacterium tuberculosis, an ethambutol (Emb) resistant clinical isolate was shown to have a significantly higher proportion of nonmannose capped arabinan termini. More drastically, the mannose capping was completely inhibited when an Emb-susceptible strain was grown in the presence of subminimal inhibitory concentration of Emb. Both cases resulted in an increase of arabinose to mannose ratio in the overall glycosyl composition of LAM. Emb, therefore, not only could affect the complete elaboration of the arabinan as found previously for LAM from Mycobacterium smegmatis resistant mutant but also could inhibit the extent of mannose capping and hence its associated biological functions in M. tuberculosis. Unexpectedly, an intrinsically Emb-resistant Mycobacterium avium isolate of smooth transparent colony morphology was found to have most of its arabinan termini capped with a single mannose residue instead of the more common dimannoside as established for LAM from M. tuberculosis. This is the first report on the LAM structure from M. avium complex, an increasingly important opportunistic infectious agent afflicting AIDS patients

  structure, virulence, lipoarabinomannan, Mycobacterium tuberculosis, tuberculosis, Mycobacterium avium Complex

  NCBI PubMed ID: 11073941
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Correspondence: delphi@lamar.colostate.edu
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA
  Methods: HPAEC, MS, enzymatic digestion
  
   
  
  Mycobacterium tuberculosis CSU19, Mycobacterium avium 2151
  CSDB ID 916 (all data & tools)

Show legend Show as text

Structure type: fragment of a bigger structure
Trivial name: arabinan in LAM
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_134619,IEDB_136104,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857717,IEDB_857718,IEDB_857722,IEDB_857723,IEDB_857726,IEDB_857727,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 1449
  Chatterjee D, Khoo K "Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects" - Glycobiology 8(2) (1998) 113-120
  

  Detailed structural and functional studies over the last decade have led to current recognition of the mycobacterial lipoarabinomannan (LAM) as a phosphatidylinositol anchored lipoglycan with diverse biological activities. Fatty acylation has been demonstrated to be essential for LAM to maintain its functional integrity although the focus has largely been on the arabinan motifs and the terminal capping function. It has recently been shown that the mannose caps may be involved not only in attenuating host immune response, but also in mediating the binding of mycobacteria to and subsequent entry into macrophages. This may further be linked to an intracellular trafficking pathway through which LAM is thought to be presented by CD1 to subsets of T-cells. The implication of LAM as major histocompatibility complex (MHC)-independent T-cell epitope and the ensuing immune response is an area of intensive studies. Another recent focus of research is the biosynthesis of arabinan which has been shown to be inhibitable by the anti-tuberculosis drug, ethambutol. The phenomenon of truncated LAM as synthesized by ethambutol resistant strains provides an invaluable handle for dissecting the array of arabinosyltransferases involved, as well as generating much needed structural variants for further structural and functional studies. It is hoped that with more systematic investigations based on clinical isolates and human cell lines, the true significance of LAM in the immunopathogenesis of tuberculosis and leprosy can eventually be explained.

  structure, Mycobacteria, lipoarabinomannan, lipoglycan, tuberculosis, CD1, phosphatidylinositol, ethambutol, lipomannan, phosphatidylinositol mannosides

  NCBI PubMed ID: 9451020
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA and Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  
   
  
  Mycobacterium
  CSDB ID 1216 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: arabinan in LAM
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_136104,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_857718,IEDB_857722,IEDB_857726,IEDB_983930,SB_136,SB_196,SB_44,SB_67,SB_72

• Article ID: 1449
  Chatterjee D, Khoo K "Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects" - Glycobiology 8(2) (1998) 113-120
  

  Detailed structural and functional studies over the last decade have led to current recognition of the mycobacterial lipoarabinomannan (LAM) as a phosphatidylinositol anchored lipoglycan with diverse biological activities. Fatty acylation has been demonstrated to be essential for LAM to maintain its functional integrity although the focus has largely been on the arabinan motifs and the terminal capping function. It has recently been shown that the mannose caps may be involved not only in attenuating host immune response, but also in mediating the binding of mycobacteria to and subsequent entry into macrophages. This may further be linked to an intracellular trafficking pathway through which LAM is thought to be presented by CD1 to subsets of T-cells. The implication of LAM as major histocompatibility complex (MHC)-independent T-cell epitope and the ensuing immune response is an area of intensive studies. Another recent focus of research is the biosynthesis of arabinan which has been shown to be inhibitable by the anti-tuberculosis drug, ethambutol. The phenomenon of truncated LAM as synthesized by ethambutol resistant strains provides an invaluable handle for dissecting the array of arabinosyltransferases involved, as well as generating much needed structural variants for further structural and functional studies. It is hoped that with more systematic investigations based on clinical isolates and human cell lines, the true significance of LAM in the immunopathogenesis of tuberculosis and leprosy can eventually be explained.

  structure, Mycobacteria, lipoarabinomannan, lipoglycan, tuberculosis, CD1, phosphatidylinositol, ethambutol, lipomannan, phosphatidylinositol mannosides

  NCBI PubMed ID: 9451020
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Institutions: Department of Microbiology, Colorado State University, Fort Collins, CO 80523, USA and Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
  
   
  
  Mycobacterium
  CSDB ID 31655 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: rest of molecule
Trivial name: lipoarabinomannan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 1690
  Brennan PJ, Nikaido H "The envelope of mycobacteria" - Annual Review of Biochemistry 64 (1995) 29-63
  

  Mycobacteria, members of which cause tuberculosis and leprosy, produce cell walls of unusually low permeability, which contribute to their resistance to therapeutic agents. Their cell walls contain large amounts of C60-C90 fatty acids, mycolic acids, that are covalently linked to arabinogalactan. Recent studies clarified the unusual structures of arabinogalactan as well as of extractable cell wall lipids, such as trehalose-based lipooligosaccharides, phenolic glycolipids, and glycopeptidolipids. Most of the hydrocarbon chains of these lipids assemble to produce an asymmetric bilayer of exceptional thickness. Structural considerations suggest that the fluidity is exceptionally low in the innermost part of bilayer, gradually increasing toward the outer surface. Differences in mycolic acid structure may affect the fluidity and permeability of the bilayer, and may explain the different sensitivity levels of various mycobacterial species to lipophilic inhibitors. Hydrophilic nutrients and inhibitors, in contrast, traverse the cell wall presumably through channels of recently discovered porins.

  NCBI PubMed ID: 7574484
  Journal NLM ID: 2985150R
  Institutions: Department of Microbiology, Colorado State University, Fort Collins 80523, USA
  
   
  
  Mycobacterium
  CSDB ID 103787 (all data & tools)

Show legend Show as text

Structure type: oligomer
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 2498
  McNeil MR, Robuck KG, Harter M, Brennan PJ "Enzymatic evidence for the presence of a critical terminal hexa-arabinoside in the cell walls of Mycobacterium tuberculosis" - Glycobiology 4 (1994) 165-173
  

  A species of Cellulomonas was isolated from soil by enrichment culture and shown to secrete enzymes capable of degrading mycobacterial cell wall arabinogalactan, both the insoluble peptidoglycan-bound and base-solubilized forms. The major degradation product was purified and characterized as a hexa-arabinofuranoside, [β-D-Araf-(1→2)-α-Araf-(1→]2→3,5-α-D-Araf-(1→5)-D-Araf. The non-reducing ends of this unit are the sites of mycolic acid attachment and, as they also appear in lipoarabinomannan (LAM), the point of mannose capping in some mycobacteria. Thus, elaboration of the structure of this focal hexasaccharide is critical to our understanding of much of the physiology and pathogenesis of mycobacteria. The extracellular enzymes of Cellulomonas sp. also released the disaccharide, α-D-Araf-(1→5)-D-Araf, from internal linear regions of arabinan and, surprisingly, convert the linear galactan backbone into cyclic oligosaccharides of the structure [→5-D-Galf-(1→6)-β-D-Galf-(1→]n where n is 2, 3 or 4. Thus, the preparation contains Schardinger-like enzyme activity. This group of enzymes are powerful tools for the dissection of the mycolylarabino-galactan-peptidoglycan (mAGP) complex of mycobacteria towards understanding its role in drug resistance, disease processes and mycobacterial physiology.

  NCBI PubMed ID: 8054716
  Journal NLM ID: 9104124
  Publisher: IRL Press at Oxford University Press
  Institutions: Department of Microbiology, Colorado State University, Fort Collins 80523
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 126933 (all data & tools)

Show legend Show as text

Structure type: fragment of a bigger structure
Aglycon: (1->5)aDAraf of arabinogalactan
Compound class: arabinogalactan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 2644
  Daffé M, Brennan PJ, McNeil M "Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by proton and carbon-13 NMR analyses" - Journal of Biological Chemistry 265 (1990) 6734-6743
  

  The peptidoglycan-bound arabinogalactan of a virulent strain of Mycobacterium tuberculosis was per-O-methylated, partially hydrolyzed with acid, and the resulting oligosaccharides reduced and O-pentadeute-rioethylated. The per-O-alkylated oligoglycosyl alditol fragments were separated by high pressure liquid chromatography and the structures of 43 of these constituents determined by 1H NMR and gas chromatography/mass spectrometry. The arabinogalactan was shown to consist of a galactan containing alternating 5-linked β-D-galactofuranosyl (Galf) and 6-linked β-D-Galf residues. The arabinan chains are attached to C-5 of some of the 6-linked Galf residues. The arabinan is comprised of at least three major structural domains. One is composed of linear 5-linked α-D-arabinofuranosyl (Araf) residues; a second consists of branched 3,5-linked α-D-Araf units substituted with 5-linked α-D-Araf residues at both branched positions. The non-reducing terminal region of the arabinan was characterized by a 3,5-linked α-D-Araf residue substituted at both branched positions with the disaccharide β-D-Araf-(1→2)-α-D-Araf. 13C NMR of intact soluble arabinogalactan established the presence of both α- and β-Araf residues in this domain. This non-reducing terminal motif apparently provides the structural basis of the dominant immunogenicity of arabinogalactan within mycobacteria. A rhamnosyl residue occupies the reducing terminus of the galactan core and may link the arabinogalactan to the peptidoglycan. Evidence is also presented for the presence of minor structural features involving terminal mannopyranosyl units. Models for most of the heteropolysaccharide are proposed which should increase our understanding of a molecule responsible for much of the immunogenicity, pathogenicity, and peculiar physical properties of the mycobacterial cell.

  NCBI PubMed ID: 2108960
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Institutions: Department of Microbiology, Colorado State University, Fort Collins 80523
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 135834 (all data & tools)

Show legend Show as text

Structure type: oligomer
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_159255,IEDB_857717,IEDB_857718

• Article ID: 2654
  McNeil M, Daffé M, Brennan PJ "Location of the mycolyl ester substituents in the cell walls of mycobacteria" - Journal of Biological Chemistry 266 (1991) 13217-13223
  

  The question of the precise location of mycolic acids, the single most distinctive cell wall entity of members of the Mycobacterium genus, has now been addressed. The free hydroxyl functions of the arabinogalactan component of the mycobacterial cell wall were O-methylated under conditions in which the mycolyl esters were not cleaved. Subsequent replacement of the mycolyl functions with O-ethyl groups resulted in an acid- and base-stable differentially O-alkylated surrogate polysaccharide, more amenable to analysis. Complete hydrolysis, reduction, acetylation, and gas chromatography/mass spectrometry revealed the unexpected finding that the mycolyl substituents were selectively and equally distributed on the 5-hydroxyl functions of terminal- and 2-linked arabinofuranosyl (Araf) residues. Further analysis of the O-alkylated cell wall through partial acid hydrolysis, NaB[2H]4 reduction, pentadeuterioethylation, and gas chromatography/mass spectrometry demonstrated that the mycolyl units are clustered in groups of four on the previously recognized nonreducing terminal pentaarabinosyl unit [β-Araf-(1→2)-α-Araf)2-3,5-α-Araf. However, only about two-thirds of the available pentasaccharide units are so substituted. Thus, the antigenicity of the arabinan component of mycobacterial cell walls may be explained by the fact that about one-third of the pentaarabinosyl units are not mycolyated and are available for interaction with the immune system. On the other hand, the extreme hydrophobicity and impenetrability of the mycobacterial cell may be explained by the same motif also acting as the fulerum for massive esterified paraffin residues. New fundamental information on the structure of mycobacterial cell walls will aid in our comprehension of its impenetrability to antibiotics and role in immunopathogenesis and persistence of disease.

  NCBI PubMed ID: 1906464
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Institutions: Department of Microbiology, Colorado State University, Fort Collins 80523
  Methods: GC-MS
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 136189 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: arabinomannan
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_136104,IEDB_140116,IEDB_141793,IEDB_141828,IEDB_141829,IEDB_141830,IEDB_141831,IEDB_143632,IEDB_144983,IEDB_152206,IEDB_153220,IEDB_153762,IEDB_153763,IEDB_1855257,IEDB_76933,IEDB_857718,IEDB_857732,IEDB_857735,IEDB_983930,SB_136,SB_191,SB_196,SB_198,SB_44,SB_67,SB_72

• Article ID: 2663
  Venisse A, Berjeaud JM, Chaurand P, Gilleron M, Puzo G "Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry" - Journal of Biological Chemistry 268 (1993) 12401-12411
  

  It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit α-D-Manp-(1→2)-α-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection.

  NCBI PubMed ID: 8509380
  Journal NLM ID: 2985121R
  Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
  Institutions: Centre National de la Recherche Scientifique, Département Glycoconjugués et Biomembranes, Toulouse, France
  Methods: 1H NMR, FAB-MS/MS, LD-MS
  
   
  
  Mycobacterium bovis BCG
  CSDB ID 186631 (all data & tools)
• Article ID: 3114
  Venisse A, Fournié JJ, Puzo G "Mannosylated lipoarabinomannan interacts with phagocytes" - European Journal of Biochemistry 231 (1995) 440-447
  

  Infection by Mycobacterium tuberculosis first involves its adhesion to mononuclear host phagocytes. Various macrophage opsonic and non-opsonic receptors are known to mediate this adhesion, with some specificity of mannosyl receptors for the more virulent strains. Mannosylated lipoarabinomannan, a major component of cell walls from M. tuberculosis and Mycobacterium bovis BCG, is endowed with mannooligosaccharide units that could mediate its binding to these latter receptors. To explore its interaction with murine immune cells by flow cytometry, we report a new procedure to fluorescently tag the polysaccharide molecules. We covalently labeled mannosylated lipoarabinomannan from M. bovis BCG with biotin, allowing formation of stable complexes with streptavidin coupled to a fluorochrome. In this work, we demonstrated that this major carbohydrate antigen interacts selectively with murine phagocytes, i.e. granulocytes and macrophages. This binding was affected by temperature and was serum- and divalent-cation-dependent. It also appears to involve a metabolically recycling protein receptor on the phagocyte surface and mannosyl aggretopes on the mannosylated lipoarabinomannan molecule. Thus, the latter may provide a means for mycobacteria to bind to and invade their host phagocytes. This molecule could constitute one of the early factors of mycobacterial virulence.

  NCBI PubMed ID: 7635156
  Publication DOI: 10.1111/j.1432-1033.1995.tb20717.x
  Journal NLM ID: 0107600
  Publisher: Oxford, UK: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
  Institutions: Departement des Glycoconjugues et Biomembranes, Laboratoire de Pharmacologie et Toxicologie Fondamentales du CNRS, Toulouse, France
  
   
  
  Mycobacterium bovis BCG, Mycobacterium tuberculosis
  CSDB ID 174784 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: arabinogalactan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 3433
  Amin AG, Goude R, Shi L, Zhang J, Chatterjee D, Parish T "EmbA is an essential arabinosyltransferase in Mycobacterium tuberculosis" - Microbiology 154(1) (2008) 240-248
  

  The Emb proteins (EmbA, EmbB, EmbC) are mycobacterial arabinosyltransferases involved in the biogenesis of the mycobacterial cell wall. EmbA and EmbB are predicted to work in unison as a heterodimer. EmbA and EmbB are involved in the formation of the crucial terminal hexaarabinoside motif [Araβ(1→2)Araα(1→5)] [Araβ(1→2)Araα(1→3)]Araα(1→5)Araα1→(Ara(6)) in the cell wall polysaccharide arabinogalactan. Studies conducted in Mycobacterium smegmatis revealed that mutants with disruptions in embA or embB are viable, although the growth rate was affected. In contrast, we demonstrate here that embA is an essential gene in Mycobacterium tuberculosis, since a deletion of the chromosomal gene could only be achieved when a second functional copy was provided on an integrated vector. Complementation of an embA mutant of M. smegmatis by M. tuberculosis embA confirmed that it encodes a functional arabinosyltransferase. We identified a promoter for M. tuberculosis embA located immediately upstream of the gene, indicating that it is expressed independently from the upstream gene, embC. Promoter activity from P(embA)((Mtb)) was sevenfold lower when assayed in M. smegmatis compared to M. tuberculosis, indicating that the latter is not a good host for genetic analysis of M. tuberculosis embA expression. P(embA)((Mtb)) activity remained constant throughout growth phases and after stress treatment, although it was reduced during hypoxia-induced non-replicating persistence. Ethambutol exposure had no effect on P(embA)((Mtb)) activity. These data demonstrate that M. tuberculosis embA encodes a functional arabinosyltransferase which is constitutively expressed and plays a critical role in M. tuberculosis.

  gene, cell wall, Mycobacterium, arabinogalactan, Mycobacterium tuberculosis, Mycobacterium smegmatis, tuberculosis

  NCBI PubMed ID: 18174142
  Journal NLM ID: 0376646
  Publisher: Washington, DC: Kluwer Academic/Plenum Publishers
  Correspondence: t.parish@qmul.ac.uk
  Institutions: Department of Microbiology, Immunology and Pathology, Colorado State University, CO 80523, USA
  Methods: GC-MS, sugar analysis, GC, genetic methods
  
   
  
  Mycobacterium smegmatis
  CSDB ID 22604 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: octylamine
Trivial name: arabinan
Contained glycoepitopes: IEDB_1309625,IEDB_857718

• Article ID: 3439
  Birch HL, Alderwick LJ, Bhatt A, Rittmann D, Krumbach K, Singh A, Bai Y, Lowary TL, Eggeling L, Besra GS "Biosynthesis of mycobacterial arabinogalactan: identification of a novel α(1→3) arabinofuranosyltransferase" - Molecular Microbiology 69(5) (2008) 1191-1206
  

  The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several antitubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-EmbB. A bioinformatics approach identified putative integral membrane proteins, MSMEG2785 in Mycobacterium smegmatis, Rv2673 in Mycobacterium tuberculosis and NCgl1822 in Corynebacterium glutamicum, with 10 predicted transmembrane domains and a glycosyltransferase motif (DDX), features that are common to the GT-C superfamily of glycosyltransferases. Deletion of M. smegmatis MSMEG2785 resulted in altered growth and glycosyl linkage analysis revealed the absence of AG α(1→3)-linked arabinofuranosyl (Araf) residues. Complementation of the M. smegmatis deletion mutant was fully restored to a wild-type phenotype by MSMEG2785 and Rv2673, and as a result, we have now termed this previously uncharacterized open reading frame, arabinofuranosyltransferase C (aftC). Enzyme assays using the sugar donor β-D-arabinofuranosyl-1-monophosphoryl-decaprenol (DPA) and a newly synthesized linear α(1→5)-linked Ara(5) neoglycolipid acceptor together with chemical identification of products formed, clearly identified AftC as a branching α(1→3) arabinofuranosyltransferase. This newly discovered glycosyltransferase sheds further light on the complexities of Mycobacterium cell wall biosynthesis, such as in M. tuberculosis and related species and represents a potential new drug target.

  biosynthesis, cell wall, glycosyltransferases, bioinformatics, Membrane Proteins, arabinogalactan, Mycobacterium tuberculosis, Mycobacterium smegmatis, tuberculosis, neoglycolipid

  NCBI PubMed ID: 18627460
  Publication DOI: 10.1111/j.1365-2958.2008.06354.x
  Journal NLM ID: 8712028
  Publisher: Blackwell Publishing
  Correspondence: g.besra@bham.ac.uk
  Institutions: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
  Methods: genetic methods, biochemical methods
  
   
  
  Mycobacterium smegmatis
  CSDB ID 22828 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: 8-aminooctanol
Trivial name: synthetic hexasaccharide
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 3594
  Pozsgay V "Recent developments in synthetic oligosaccharide-based bacterial vaccines" - Current Topics in Medicinal Chemistry 8(2) (2008) 126-140
  

  Synthetic advances made possible chemical assembly of complex oligosaccharide fragments of polysaccharide domains on the surface of human pathogenic bacteria. These oligosaccharides may be recognized by antibodies raised against high molecular weight, native, polysaccharides. In addition to their antigenicity, synthetic oligosaccharides can also function as haptens in their protein conjugates that can elicit not only oligo- but also polysaccharide-specific IgG antibodies in animal models and in humans. A major milestone in the development of new generation vaccines was the demonstration that protein conjugates of synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b are as efficacious in preventing childhood meningitis and other diseases as is the corresponding licensed commercial vaccine containing the bacterial polysaccharide. The lessons learnt in this and other endeavors described herein are manifold. For example, they teach us about the significance of the oligosaccharide epitope size, the number of their copies per protein in the conjugate, the possible effect of the spacer on anti-saccharide immune response, and the proper choice of the carrier protein combined with the selection of the animal model. The H. influenzae b story also teaches us that that the synthetic approach can be commercially viable.

  Haemophilus influenzae, Streptococcus pneumoniae, Oligosaccharides, Shigella dysenteriae type 1, keyhole limpet hemocyanin, keyhole limpet hemocyanine

  NCBI PubMed ID: 18289082
  Journal NLM ID: 101119673
  Publisher: Bentham Science Publishers
  Correspondence: pozsgayv@mail.nih.gov
  Institutions: National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr., MSC 2423, Bethesda, MD 20892-2423, USA
  Methods: chemical synthesis
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 23502 (all data & tools)