Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects

Detailed structural and functional studies over the last decade have led tocurrent recognition of the mycobacterial lipoarabinomannan (LAM) as aphosphatidylinositol anchored lipoglycan with diverse biologicalactivities. Fatty acylation has been demonstrated to be essential for LAMto maintain its functional integrity although the focus has largely been onthe arabinan motifs and the terminal capping function. It has recently beenshown that the mannose caps may be involved not only in attenuating hostimmune response, but also in mediating the binding of mycobacteria to andsubsequent entry into macrophages. This may further be linked to anintracellular trafficking pathway through which LAM is thought to bepresented by CD1 to subsets of T-cells. The implication of LAM as majorhistocompatibility complex (MHC)-independent T-cell epitope and the ensuingimmune response is an area of intensive studies. Another recent focus ofresearch is the biosynthesis of arabinan which has been shown to beinhibitable by the anti- tuberculosis drug, ethambutol. The phenomenon oftruncated LAM as synthesized by ethambutol resistant strains provides aninvaluable handle for dissecting the array of arabinosyltransferasesinvolved, as well as generating much needed structural variants for furtherstructural and functional studies. It is hoped that with more systematicinvestigations based on clinical isolates and human cell lines, the truesignificance of LAM in the immunopathogenesis of tuberculosis and leprosycan eventually be explained.