title: Truncated structural variants of lipoarabinomannan in Mycobacterium leprae and an ethambutol-resistant strain of Mycobacterium tuberculosis.
abstract: Current knowledge on the structure of lipoarabinomannan (LAM) has resulted primarily from detailed studies on a few selected laboratory strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis. Our previous work was the first to report on the salient structural features of M. tuberculosis clinical isolates and demonstrated significant structural variations. A prime effort is to correlate a particular structural characteristic with observed differences in eliciting an immunobiological response, especially in the context of CD1-restricted presentation of LAM to T cells. T cell clones derived from the cutaneous lesions of leprosy patients have been shown to recognize specifically LAM from Mycobacterium leprae and not from M. tuberculosis Erdman or H37Rv. Herein we provide further fine structural data on LAM from M. leprae (LepLAM) and a tuberculosis clinical isolate, CSU20 (CSU20LAM), which was unexpectedly recognized by the supposedly LepLAM-specific CD1-restricted T cell clones. In comparison with the de facto laboratory LAM standard from M. tuberculosis H37Rv (RvLAM), LepLAM derived from in vivo grown M. leprae is apparently simpler in its arabinan architecture with a high degree of exposed, non-mannose-capped termini. On the other hand, CSU20, an ethambutol-resistant clinical isolate, makes a vastly heterogeneous population of LAM ranging from rather small and non-mannose-capped to full-length and fully capped variants. LepLAM and CSU20LAM contain a higher level of succinylation than RvLAM, which, in the context of truncated or less elaborated arabinan, may contribute to selective recognition by T cells. LAM from all species could be resolved into discrete forms by isoelectric focusing based apparently on their arabinan heterogeneity. In the light of our current and more recent findings, we reason that all immunobiological data should be cautiously interpreted and that the actual LAM variants that may be present in vivo during infection and pathogenesis need to be taken into consideration.
authors.affiliation: Department of Microbiology, Colorado Stae University, Fort Collins 80523, USA.
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.forename: Angela M
authors.initials: AM
authors.lastname: Marques
authors.forename: Achim
authors.initials: A
authors.lastname: Treumann
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rithner
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: Delphi
authors.initials: D
authors.lastname: Chatterjee
mesh_terms: D015153:Blotting, Western; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004977:Ethambutol / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry; D009005:Monosaccharides / Q000378:metabolism; D009166:Mycobacterium leprae / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D043323:alpha-Mannosidase / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009005:Monosaccharides; C050016:lipoarabinomannan; D004977:Ethambutol; D043323:alpha-Mannosidase; D008358:Mannose