ArticleProceedings of the National Academy of Sciences of the United States of America2010
A truncated lipoglycan from mycobacteria with altered immunological properties.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- A new role for lipoproteins LpqZ and FecB in orchestrating mycobacterial cell envelope biogenesis.mBio · 2026Article
- Contribution of Proteins to Membrane and Cell Wall Structures in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adaptedProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Enhanced immunogenicity ofCell surface (Amsterdam, Netherlands) · 2022Article
- Article
- Polysaccharide length affects mycobacterial cell shape and antibiotic susceptibility.Science advances · 2020Article
- The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system.The Biochemical journal · 2020Review
- Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 fromInternational journal of molecular sciences · 2019Article
- TheThe Biochemical journal · 2019Review
- Cell Type Specific Expression of Toll-Like Receptors in Human Brains and Implications in Alzheimer's Disease.BioMed research international · 2019Review
- The singularCell surface (Amsterdam, Netherlands) · 2018Article
- Review
- Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target.Parasitology · 2018Review
- Disruption of Mycobacterial AftB Results in Complete Loss of Terminal β(1 → 2) Arabinofuranose Residues of Lipoarabinomannan.ACS chemical biology · 2017Article
- Identification of a Novel Mycobacterial Arabinosyltransferase Activity Which Adds an Arabinosyl Residue to α-d-Mannosyl Residues.ACS chemical biology · 2016Article
- The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan.Cold Spring Harbor perspectives in medicine · 2015Review
- Elucidation of a protein-protein interaction network involved in Corynebacterium glutamicum cell wall biosynthesis as determined by bacterial two-hybrid analysis.Glycoconjugate journal · 2014Article
- The sweet tooth of bacteria: common themes in bacterial glycoconjugates.Microbiology and molecular biology reviews : MMBR · 2014Review
- Article
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Maintenance of cell-wall integrity in Mycobacterium tuberculosis is essential and is the target of several antitubercular drugs. For example, ethambutol targets arabinogalactan and lipoarabinomannan (LAM) biosynthesis through the inhibition of several arabinofuranosyltransferases. Apart from their role in cell-wall integrity, mycobacterial LAMs also exhibit important immunomodulatory activities. Here we report the isolation and detailed structural characterization of a unique LAM molecule derived from Mycobacterium smegmatis deficient in the arabinofuranosyltransferase AftC (AftC-LAM). This mutant LAM expresses a severely truncated arabinan domain completely devoid of 3,5-Araf-branching residues, revealing an intrinsic involvement of AftC in the biosynthesis of LAM. Furthermore, we found that ethambutol efficiently inhibits biosynthesis of the AftC-LAM arabinan core, unambiguously demonstrating the involvement of the arabinofuranosyltransferase EmbC in early stages of LAM-arabinan biosynthesis. Finally, we demonstrate that AftC-LAM exhibits an enhanced proinflammatory activity, which is due to its ability to activate Toll-like receptor 2 (TLR2). Overall, our efforts further describe the mechanism of action of an important antitubercular drug, ethambutol, and demonstrate a role for specific arabinofuranosyltransferases in LAM biosynthesis. In addition, the availability of sufficient amounts of chemically defined wild-type and isogenic truncated LAMs paves the way for further investigations of the structure-function relationship of TLR2 activation by mycobacterial lipoglycans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.