{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:08:00Z","timestamp":1785424080285,"version":"3.56.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Mycobacterium avium-intracellulare<\/jats:italic>\n                      complex (MAC) infections are the most common nontuberculous mycobacterial infections, and ethambutol (EMB) is one of the main therapeutic agents used to treat MAC infections. However, the EMB resistance profile and its resistance mechanisms in\n                      <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                      remain poorly understood. This study determined the minimum inhibitory concentration (MIC) of 40\n                      <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                      clinical strains, revealing that 97.5% (39\/40) of the strains were intermediate (MIC = 4 \u00b5g\/mL) or resistant (MIC \u2265 8 \u00b5g\/mL) to EMB. One susceptible clinical isolate strain 245 (MIC = 2 \u00b5g\/mL) was picked for EMB-resistant mutant isolation, and a total of 121 resistant mutants were isolated and subjected to whole-genome sequencing or Sanger sequencing. Integrated analysis revealed that 94.21% (114\/121) of the mutants carried mutations in the\n                      <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                      gene, which encodes decaprenylphosphoryl-\u03b2-D-5-phosphoribose (DPPR) synthase\u2014an enzyme involved in cell wall biosynthesis that has been associated with high-level EMB resistance in\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      . Complementation with the wild-type\n                      <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                      gene restored EMB susceptibility in EMB-resistant mutants and clinical strain 322 (EMB MIC = 64 \u00b5g\/mL) with\n                      <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                      mutation, reducing the MICs from 32 to 4 \u03bcg\/mL and from 64 to 8 \u03bcg\/mL, respectively. This study indicates that the\n                      <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                      mutation is the major mechanism of EMB resistance in\n                      <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                      , which should facilitate the development of molecular tests for rapid detection of resistance in this organism.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study identified\n                        <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                        as a key gene associated with ethambutol (EMB) resistance in\n                        <jats:italic toggle=\"yes\">Mycobacterium avium<\/jats:italic>\n                        , a finding which has not previously been reported. Furthermore, although\n                        <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                        has been linked to EMB resistance in\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        (MTB), mutations in this gene account for only a small proportion of EMB-resistant MTB isolates. In contrast, our study showed that\n                        <jats:italic toggle=\"yes\">ubiA<\/jats:italic>\n                        played a major role in EMB resistance in\n                        <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                        . Our findings contribute to the development of molecular assays for rapid detection of EMB resistance in\n                        <jats:italic toggle=\"yes\">M. avium<\/jats:italic>\n                        and highlight the distinct main resistance mechanisms across different bacterial species to the same antibiotic.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03151-25","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:51:16Z","timestamp":1774263076000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Mutations in the\n                    <i>ubiA<\/i>\n                    gene are the major mechanism of ethambutol resistance in\n                    <i>Mycobacterium avium<\/i>"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4054-5865","authenticated-orcid":false,"given":"Yuwei","family":"Qiu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0232r4451","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, 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for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhi","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0232r4451","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of 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Performance standards for susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes. 2nd ed. CLSI Supplement M24S. 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