Glycobiology, Vol 8, 113-120, Copyright © 1998 by Society for Glycobiology
D Chatterjee and KH Khoo
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.
ORIGINAL ARTICLES
Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects
Department of Microbiology, Colorado State University, Fort Collins 80523, USA.
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