Lipoarabinomannan: structure and functions of a glycolipid involved in tuberculosis pathogenicity

Tuberculosis is the predominant cause of morbidity and mortality worldwide, infecting 8 million and killing 3 million people annually. The current situation is exacerbated by the HIV pandemic and the increased prevalence of multiple resistant strains of M. tuberculosis, while vaccine prophylaxis using BCG is unsatisfactory in many parts of the world Mycobacteria have evolved many specific adaptations that enable them to infect and survive within host cells, Such host-pathogen interactions are mediated by specialized molecules, in particular those associated with the unique cellular envelope. Lipoarabinomannan (LAM) is regarded is the "lipopolysaccharide. of mycobacteria" and is an important virulence factor. Its terminal mannose cars may be involved-mot only in attenuating the host immune response but also in mediating the binding of mycobacteria to, and subsequent entry into macrophages. This may be further linked to an intracellular trafficking pathway through which LAM is presented by CD1 to T-cell subsets. More systematic genome type investigations of LAM biogenesis may reveal the true significance of this macromolecule In the immunopathogenesis of tuberculosis. As a consequence, the identification of new drug targets will permit the development of novel therapies against tuberculosis and other mycobacterial-related infections which may now be. visualized through the advent of the recently sequenced M. tuberculosis genome.