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Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Polysaccharide Succinylation Enhances the Intracellular Survival of Mycobacterium abscessus
Zuzana Palčeková1, Martine Gilleron2, Shiva Kumar Angala1
1Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523-1682, United States.
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.
Insights
The study reveals unique structures of Mycobacterium abscessus cell envelope glycoconjugates, phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM). Polysaccharide succinylation significantly impacts M. abscessus virulence and host cell interactions.
Area of Science:
- Microbiology
- Glycobiology
- Immunology
Background:
- Cell envelope glycoconjugates like lipoarabinomannan (LAM), phosphatidylinositol mannosides (PIMs), and lipomannan (LM) are crucial for Mycobacterium tuberculosis pathogenesis.
- The role of these molecules in nontuberculous mycobacteria, particularly Mycobacterium abscessus, remains largely unexplored.
Purpose of the Study:
- To elucidate the structures of PIMs, LM, and LAM in Mycobacterium abscessus.
- To investigate the biological significance of these glycoconjugates, especially polysaccharide succinylation, in M. abscessus virulence.
Main Methods:
- Structural analysis of M. abscessus PIMs, LM, and LAM.
- In vitro assays to assess the role of polysaccharide succinylation in host cell entry and survival.
Main Results:
- Mycobacterium abscessus PIMs, LM, and LAM exhibit unique structural features compared to other mycobacteria, including specific mannosyl substituents and arabinan domain modifications.
- Polysaccharide succinylation was identified as a key factor enhancing M. abscessus entry and survival within human macrophages and epithelial cells.
Conclusions:
- The distinct structures of M. abscessus cell envelope glycoconjugates contribute to its unique physiology and pathogenicity.
- Polysaccharide succinylation is a critical virulence factor for M. abscessus, modulating host-pathogen interactions and validating cell envelope polysaccharides as significant virulence modulators.
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