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The ability of\n              <jats:italic>M. abscessus<\/jats:italic>\n              to establish a chronic infection in the lung relies on a series of adaptive mutations impacting, in part, global regulators and cell envelope biosynthetic enzymes. One of the genes under strong evolutionary pressure during host adaptation is\n              <jats:italic>ubiA<\/jats:italic>\n              , which participates in the elaboration of the arabinan domains of two major cell envelope polysaccharides: arabinogalactan (AG) and lipoarabinomannan (LAM). We here show that patient-derived UbiA mutations not only cause alterations in the AG, LAM, and mycolic acid contents of\n              <jats:italic>M. abscessus<\/jats:italic>\n              but also tend to render the bacterium more prone to forming biofilms while evading uptake by innate immune cells and enhancing their pro-inflammatory properties. The fact that the effects of UbiA mutations on the physiology and pathogenicity of\n              <jats:italic>M. abscessus<\/jats:italic>\n              were impacted by the rough or smooth morphotype of the strain suggests that the timing of their selection relative to morphotype switching may be key to their ability to promote chronic persistence in the host.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Multidrug-resistant pulmonary infections caused by\n                <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                and subspecies are increasing in the U.S.A. and globally. Little is known of the mechanisms of pathogenicity of these microorganisms. We have identified single-nucleotide polymorphisms (SNPs) in a gene involved in the biosynthesis of two major cell envelope polysaccharides, arabinogalactan and lipoarabinomannan, in lung-adapted isolates from 13 patients. Introduction of these individual SNPs in a reference\n                <jats:italic>M. abscessus<\/jats:italic>\n                strain allowed us to study their impact on the physiology of the bacterium and its interactions with immune cells. The significance of our work is in identifying some of the mechanisms used by\n                <jats:italic>M. abscessus<\/jats:italic>\n                to colonize and persist in the human lung, which will facilitate the early detection of potentially more virulent clinical isolates and lead to new therapeutic strategies. Our findings may further have broader biomedical impacts, as the\n                <jats:italic>ubiA<\/jats:italic>\n                gene is conserved in other tuberculous and non-tuberculous mycobacterial pathogens.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00322-25","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:01:28Z","timestamp":1741957288000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Cell envelope polysaccharide modifications alter the surface properties and interactions of\n            <i>Mycobacterium abscessus<\/i>\n            with innate immune cells in a morphotype-dependent manner"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-6407","authenticated-orcid":false,"given":"Elena","family":"Lian","sequence":"first","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-9141","authenticated-orcid":true,"given":"Juan M.","family":"Belardinelli","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"De","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun Prasad","family":"Pandurangan","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute","place":["Trumpington, UK"]},{"name":"Cambridge Centre for AI in Medicine, University of Cambridge","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva K.","family":"Angala","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Pal\u010dekov\u00e1","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E.","family":"Grzegorzewicz","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine M.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, Wellcome Sanger Institute","place":["Hinxton, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom L.","family":"Blundell","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute","place":["Trumpington, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":true,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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