Polysaccharide Succinylation Enhances the Intracellular Survival of Mycobacterium abscessus

Abstract

Lipoarabinomannan (LAM) and its biosynthetic precursors, phosphatidylinositol mannosides (PIMs) and lipomannan (LM) play important roles in the interactions of Mycobacterium tuberculosis with phagocytic cells and the modulation of the host immune response but nothing is currently known of the impact of these cell envelope glycoconjugates on the physiology and pathogenicity of nontuberculous mycobacteria. We here report on the structures of Mycobacterium abscessus PIM, LM and LAM. Intriguingly, these structures differ from those reported previously in other mycobacterial species in several respects including the presence of a methyl substituent on one of the mannosyl residues of PIMs as well as the PIM anchor of LM and LAM, the size and branching pattern of the mannan backbone of LM and LAM, and the modification of the arabinan domain of LAM with both succinyl and acetyl substituents. Investigations into the biological significance of some of these structural oddities point to the important role of polysaccharide succinylation on the ability of M. abscessus to enter and survive inside human macrophages and epithelial cells and validate for the first time cell envelope polysaccharides as important modulators of the virulence of this emerging pathogen.