Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction.

Approximately one third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. This bacterium has an unusual lipid rich cell wall containing a vast repertoire of antigens, providing a hydrophobic impermeable barrier against chemical drugs, thus representing an attractive target for vaccine and drug development. Apart from the mycolyl-arabinogalactan-peptidoglycan (mAGP) complex, mycobacteria possess several immunomodulatory constituents, notably lipomannan (LM) and lipoarabinomannan (LAM). The availability of whole genome sequences of M. tuberculosis and related bacilli over the past decade, has led to the identification and functional characterization of various enzymes and potential drug targets involved in the biosynthesis of these glycoconjugates. Both LM and LAM possess highly variable chemical structures, which interact with different receptors of the immune system during host-pathogen interactions, such as Toll-Like Receptors (TLR-2), and C-type lectins. Recently, the availability of mutants defective in the synthesis of these glycoconjugates in mycobacteria and the closely related bacterium, Corynebacterium glutamicum, has opened the door for host-pathogen interaction studies, as well as, providing attenuated strains of mycobacteria for the development of new vaccine candidates. This review provides a comprehensive account of the structure, biosynthesis and immunomodulatory properties of these important glycoconjugates.