ArticlePLoS pathogens2016
Metabolic Network for the Biosynthesis of Intra- and Extracellular α-Glucans Required for Virulence of Mycobacterium tuberculosis.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
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- Mycobacterium tuberculosis bacteriology and immunity necessitate a multi-pronged immune strategy for vaccination.NPJ vaccines · 2026Review
- Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution.Genome medicine · 2025Article
- Metabolic rewiring of isoniazid sensitivity inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biosynthesis and Fatty Acid- and Cation-Binding Properties ofACS infectious diseases · 2025Article
- Association Analysis of the Genomic and Functional Characteristics of HalotolerantMicroorganisms · 2025Article
- Ovine and Caprine Strains ofMicroorganisms · 2024Article
- Architecture, Function, Regulation, and Evolution of α-Glucans Metabolic Enzymes in Prokaryotes.Chemical reviews · 2024Review
- Gallein and isoniazid act synergistically to attenuatebioRxiv : the preprint server for biology · 2024Article
- Gallein potentiates isoniazid's ability to suppressFrontiers in microbiology · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Pseudomonas syringae addresses distinct environmental challenges during plant infection through the coordinated deployment of polysaccharides.Journal of experimental botany · 2022Article
- PPE51 mediates uptake of trehalose across the mycomembrane of Mycobacterium tuberculosis.Scientific reports · 2022Article
- Synthesis of CFrontiers in chemistry · 2022Article
- Comparative Genomics of Members of the GenusFrontiers in microbiology · 2022Article
- Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages.PLoS pathogens · 2021Article
- Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope.Chemical reviews · 2021Review
- Trehalose and α-glucan mediate distinct abiotic stress responses in Pseudomonas aeruginosa.PLoS genetics · 2021Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Mycobacterium tuberculosis synthesizes intra- and extracellular α-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the α-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of α-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in α-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways. We now show that α-glucan in mycobacteria is exclusively assembled intracellularly utilizing the building block α-maltose-1-phosphate as the substrate for the maltosyltransferase GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some α-glucan is exported to form the α-glucan capsule. There is an unexpected convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate α-maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known, we have now established that GlgA forms this phosphosugar from ADP-glucose and glucose 1-phosphate 1000-fold more efficiently than its hitherto described glycogen synthase activity. The two routes are connected by the common precursor ADP-glucose, allowing compensatory flux from one route to the other. Having elucidated this unexpected configuration of the metabolic pathways underlying α-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant devoid of α-glucan could be constructed, showing a direct link between the GlgE pathway, α-glucan biosynthesis and virulence in a mouse infection model.
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