MYCOBACTERIAL LIPOARABINOMANNAN - AN EXTRAORDINARY LIPOHETEROGLYCAN WITH PROFOUND PHYSIOLOGICAL-EFFECTS

Detailed structural and functional studies over the last decade have l ed 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 large ly been on the arabinan motifs and the terminal capping function, It h as 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 fu rther be linked to an intracellular trafficking pathway through which LAM is thought to be presented by CD1 to subsets of T-cells. The impli cation of LAM as major histocompatibility complex (MHC)-independent T- cell epitope and the ensuing immune response is an area of intensive s tudies, Another recent focus of research is the biosynthesis of arabin an which has been shown to be inhibitable by the anti-tuberculosis dru g, ethambutol. The phenomenon of truncated LAM as synthesized by etham butol resistant strains provides an invaluable handle for dissecting t he array of arabinosyltransferases involved, as well as generating muc h needed structural variants for further structural and functional stu dies. It is hoped that with more systematic investigations based on cl inical isolates and human cell lines, the true significance of LAM in the immunopathogenesis of tuberculosis and leprosy can eventually be e xplained.