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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

References to other databases: GTC:G94972HI, GlycomeDB:25316
Structural formula & atomic coordinates
Sweet-II 3D model
Show glycosyltransferases

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

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