{"doi":"10.1016/j.jbc.2022.101678","title":"Tailor made: New insights into lipoarabinomannan structure may improve TB diagnosis","abstract":"Detecting the mycobacterial glycolipid lipoarabinomannan (LAM) in urine by anti-LAM antibodies fills a gap in the diagnostic armamentarium of much needed simple rapid tests for tuberculosis, but lacks high sensitivity in all patient groups. A better understanding of LAM structure from clinically relevant strains may allow improvements in diagnostic performance. De et al. have recently determined the structures of LAM from three epidemiologically important lineages of Mycobacterium tuberculosis and probed their interaction with an anti-LAM monoclonal antibody. Their results not only identify a series of tailoring modifications that impact antibody binding but also provide a roadmap for improving U-LAM-based diagnostics. Detecting the mycobacterial glycolipid lipoarabinomannan (LAM) in urine by anti-LAM antibodies fills a gap in the diagnostic armamentarium of much needed simple rapid tests for tuberculosis, but lacks high sensitivity in all patient groups. A better understanding of LAM structure from clinically relevant strains may allow improvements in diagnostic performance. De et al. have recently determined the structures of LAM from three epidemiologically important lineages of Mycobacterium tuberculosis and probed their interaction with an anti-LAM monoclonal antibody. Their results not only identify a series of tailoring modifications that impact antibody binding but also provide a roadmap for improving U-LAM-based diagnostics. A host of mycobacterial species are found in nature, ranging from environmental organisms that are nonpathogenic in most humans to those that cause serious disease (1Magee G.M. Ward A.C. Genus I. Mycobacterium Lehmann and Neumann 1896, 363AL.in: Goodfellow M. Kampfer P. Busse H.J. Trujillo M.E. Suzuki K. Ludwig W. Whitman W. Bergey's Manual of Systematic Bacteriology. Springer, New York, NY2012: 312-375Google Scholar). The disease tuberculosis (TB), an age-old scourge, arises from infection by the most notorious of all mycobacteria, Mycobacterium tuberculosis (Mtb). Around a quarter of the world is estimated to have latent Mtb infection, and 5 to 10% develop disease over their lifetime, causing over 10 million new cases with 1.5 million associated deaths annually (2Boom W.H. Schaible U.E. Achkar J.M. The knowns and unknowns of latent Mycobacterium tuberculosis infection.J. Clin. Invest. 2021; 131e136222Google Scholar). A characteristic feature of mycobacteria is their unusual cell wall, which is composed primarily of polysaccharides and glycolipids with unique and atypical structures (3Angala S.k. Palčeková Z. Belardinelli J.M. Jackson M. Covalent modifications of polysaccharides in mycobacteria.Nat. Chem. Biol. 2018; 14: 193-198Google Scholar). These molecules protect the organism from its environment, modulate the host immune response during infection, and play important roles in the pathogenesis of Mtb infection (3Angala S.k. Palčeková Z. Belardinelli J.M. Jackson M. Covalent modifications of polysaccharides in mycobacteria.Nat. Chem. Biol. 2018; 14: 193-198Google Scholar). A major component of the mycobacterial cell wall is the glycolipid lipoarabinomannan (LAM), which constitutes 15% of the Mtb mass and is a potent immunomodulator and inducer of antibodies (4Correia-Neves M. Sundling C. Cooper A. Källenius G. Lipoarabinomannan in active and passive protection against tuberculosis.Front. Immunol. 2019; 10: 1968Google Scholar). Moreover, detection of LAM in urine (U-LAM) by anti-LAM antibodies is the basis of a simple TB point-of-care diagnostic (5Flores J. Cancino J.C. Chavez-Galan L. Lipoarabinomannan as a point-of-care assay for diagnosis of tuberculosis: How far are we to use it?.Front. Microbiol. 2021; 12: 638047Google Scholar). Historically, the utility of this diagnostic has been limited to individuals with suppressed immunity, for example, HIV+ individuals, because they have higher Mtb burden and thus a higher amount of antigen shed into the urine, although recent improvements in U-LAM ","journal":"Journal of Biological Chemistry","year":2022,"id":290805,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317195,"name":"Jacqueline M. Achkar","orcid":"0000-0002-5227-7293","position":1,"is_corresponding":false},{"id":287963,"name":"Todd L. Lowary","orcid":"0000-0002-8331-8211","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T00:30:30.639224Z","pmid":"35122792","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}