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: 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: 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: 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: 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: 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)

Show legend Show as text

Structure type: oligomer
Aglycon: arabinan-LAM-mannan
Trivial name: lipoarabinomannan (LAM)
Contained glycoepitopes: IEDB_130701,IEDB_1309625,IEDB_134619,IEDB_141793,IEDB_144983,IEDB_152206,IEDB_153220,IEDB_857717,IEDB_857718,IEDB_983930,SB_198,SB_44,SB_67,SB_72

• Article ID: 5105
  Angala SK, McNeil MR, Shi L, Joe M, Pham H, Zuberogoitia S, Nigou J, Boot CM, Lowary TL, Gilleron M, Jackson M "Biosynthesis of the Methylthioxylose Capping Motif of Lipoarabinomannan in Mycobacterium tuberculosis" - ACS Chemical Biology 12(3) (2017) 682-691
  

  Lipoarabinomannan (LAM) is a lipoglycan found in abundant quantities in the cell envelope of all mycobacteria. The nonreducing arabinan termini of LAM display species-specific structural microheterogeneity that impacts the biological activity of the entire molecule. Mycobacterium tuberculosis, for instance, produces mannoside caps made of one to three α-(1 → 2)-Manp-linked residues that may be further substituted with an α-(1→4)-linked methylthio-d-xylose (MTX) residue. While the biological functions and catalytic steps leading to the formation of the mannoside caps of M. tuberculosis LAM have been well established, the biosynthetic origin and biological relevance of the MTX motif remain elusive. We here report on the discovery of a five-gene cluster dedicated to the biosynthesis of the MTX capping motif of M. tuberculosis LAM, and on the functional characterization of two glycosyltransferases, MtxS and MtxT, responsible, respectively, for the production of decaprenyl-phospho-MTX (DP-MTX) and the transfer of MTX from DP-MTX to the mannoside caps of LAM. Collectively, our NMR spectroscopic and mass spectrometric analyses of mtxS and mtxT overexpressors and knockout mutants support a biosynthetic model wherein the conversion of 5'-methylthioadenosine, which is a ubiquitous byproduct of spermidine biosynthesis, into 5'-methylthioribose-1-phosphate precedes the formation of a 5'-methylthioribose nucleotide sugar, followed by the epimerization at C-3 of the ribose residue, and the transfer of MTX from the nucleotide sugar to decaprenyl-phosphate yielding the substrate for transfer onto LAM. The conservation of the MTX biosynthetic genes in a number of Actinomycetes suggests that this discrete glycosyl substituent may be more widespread in prokaryotes than originally thought.

  Mycobacterium, lipoarabinomannan, tuberculosis, methylthioxylose

  NCBI PubMed ID: 28075556
  Publication DOI: 10.1021/acschembio.6b01071
  Journal NLM ID: 101282906
  Publisher: Washington, DC: American Chemical Society
  Correspondence: Mary.Jackson@colostate.edu
  Institutions: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University , Fort Collins, Colorado 80523-1682, United States, Alberta Glycomics Centre and Department of Chemistry, The University of Alberta, Edmonton, AB, Canada, Institut de Pharmacologie et de Biologie Structurale , Université de Toulouse, CNRS, UPS, 205 route de Narbonne, F-31077 Toulouse, France, Central Instrumentation Facility, Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523-1872, United States
  Methods: 13C NMR, 1H NMR, NMR-2D, PCR, SDS-PAGE, DNA techniques, MS/MS, genetic methods, biochemical methods, LC-MS
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 12042 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: arabinogalactan
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_136095,IEDB_137472,IEDB_137473,IEDB_149137,IEDB_149176,IEDB_159255,IEDB_190606,IEDB_857717,IEDB_857718,IEDB_857720,IEDB_885812

• Article ID: 5123
  Angala SK, Palčeková Z, Belardinelli JM, Jackson M "Covalent modifications of polysaccharides in mycobacteria" - Nature Chemical Biology 14(3) (2018) 193-198
  

  Mycobacteria produce carbohydrates of exceptional structures that are covalently modified by unique substituents, whose functional characterization could expand our understanding of how mycobacteria adapt to their environment.

  polysaccharides, modification, Mycobacteria, covalent, arabinogalactan (AG), lipoarabinomannan (LAM), lipomannan (LM)

  NCBI PubMed ID: 29443974
  Publication DOI: 10.1038/nchembio.2571
  Journal NLM ID: 101231976
  Publisher: New York, NY: Nature Publishing Group
  Correspondence: Mary.Jackson@ColoState.EDU
  Institutions: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA
  
   
  
  Mycobacterium tuberculosis, Mycobacterium bovis BCG, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium microti, Mycobacterium avium, Mycobacterium smegmatis
  CSDB ID 12865 (all data & tools)

Show legend Show as text

Structure type: fragment of a bigger structure
Trivial name: arabinofuran
Compound class: cell wall polysaccharide
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718,IEDB_857720,IEDB_857736

• Article ID: 5188
  Micoli F, Costantino P, Adamo R "Potential targets for next generation anti-microbial glycoconjugate vaccines" - FEMS Microbiology Reviews 42(3) (2018) 388-423
  

  Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines.Recent analysis from WHO/CHO underpins alarming concern towards antibiotic resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyses structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

  carbohydrates, glycoconjugates, vaccines, glycoengineering, antimicrobial resistance

  NCBI PubMed ID: 29547971
  Publication DOI: 10.1093/femsre/fuy011
  Journal NLM ID: 8902526
  Publisher: Oxford University Press
  Correspondence: Roberto Adamo
  Institutions: GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 12726 (all data & tools)

Show legend Show as text

Structure type: structural motif or average structure
Trivial name: branched hexaarabinofuranoside (Ara6)
Compound class: lipoarabinomannan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 5224
  Turner J, Torrelles JB "Mannose-capped lipoarabinomannan in Mycobacterium tuberculosis pathogenesis" - Pathogens and Disease 76(4) (2018) fty026
  

  Mannose-capped lipoarabinomannan (ManLAM), present in all members of the Mycobacterium tuberculosis complex and in other pathogenic Mycobacterium spp, is a high molecular mass amphipathic lipoglycan with a defined critical role in mycobacterial survival during infection. In particular, ManLAM is well-characterized for its importance in providing M. tuberculosis a safe portal of entry to phagocytes, regulating the intracellular trafficking network, as well as immune responses of infected host cells. These ManLAM immunological characteristics are thought to be linked to the subtle but unique and well-defined structural characteristics of this molecule, including but not limited to the degree of acylation, the length of the D-mannan and D-arabinan cores, the length of the mannose caps, as well as the presence of other acidic constituents such as succinates, lactates and/or malates, and also the presence of 5-methylthioxylosyl. The impact of all these structural features on ManLAM spatial conformation and biological functions during M. tuberculosis infection is still uncertain. In this review, we dissect the relationship between ManLAM structure and biological function addressing how this relationship determines M. tuberculosis interactions with host cells, and how it aids this exceptional pathogen during the course of infection.

  Mycobacterium tuberculosis, tuberculosis, biological functions, host cell response, mannose-capped lipoarabinomannan

  Publication DOI: 10.1093/femspd/fty026
  Journal NLM ID: 101595366
  Publisher: Oxford Oxford University Press
  Correspondence: jtorrelles@txbiomed.org
  Institutions: Tuberculosis Group, Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78227-5302. Tel: 210-258-9448
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 12989 (all data & tools)

Show legend Show as text

Structure type: oligomer
Aglycon: (->5) cell wall
Compound class: arabinan
Contained glycoepitopes: IEDB_1309625,IEDB_134619,IEDB_857717,IEDB_857718

• Article ID: 5631
  Islam M, Gayatri G, Hotha S "Influence of steric crowding on diastereoselective arabinofuranosylations" - Journal of Organic Chemistry 80(16) (2015) 7937-7945
  

  The occurrence of arabinofuranosides on the cell surface of Mycobacterium tuberculosis (Mtb) and their significance in controlling disease spurred interest in developing strategies for their diastereoselective synthesis. Mtb uses enzymes to achieve diastereoselectivity through noncovalent interactions. Of the two possible glycosidic linkages, chemically, 1,2-trans linkage is relatively easy to synthesize by taking advantage of neighboring group participation, whereas synthesis of the 1,2-cis linkage is notoriously difficult. In this article, stereochemical effects on the diastereoselectivity of arabinofuranosidation are investigated with thiopyridyl, imidate, and thiotolyl donors as well as differently crowded glycosyl acceptors; subtle differences in the stereochemical environment of the acceptors were observed to alter the diastereoselectivity of the furanoside formation. Results from this endeavor suggest that 1,2-cis arabinofuranosides can be synthesized conveniently by conducting the reaction at lower temperature on sterically demanding and less reactive substrates

  cell wall, Mycobacterium tuberculosis, stereochemistry, arabinofuranosides

  NCBI PubMed ID: 26195010
  Publication DOI: 10.1021/acs.joc.5b00964
  Journal NLM ID: 2985193R
  Publisher: Columbus, OH: American Chemical Society
  Correspondence: s.hotha@iiserpune.ac.in
  Institutions: Department of Chemistry, Indian Institute of Science Education and Research, Pune, India, Molecular Modelling Group, Indian Institute of Chemical Technology, Hyderabad, India
  Methods: 13C NMR, 1H NMR, IR, TLC, chemical synthesis, UV, optical rotation measurement, ESI-TOF-MS, UPLC-MS
  
   
  
  Mycobacterium tuberculosis
  CSDB ID 47841 (all data & tools)