{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:53Z","timestamp":1788269033823,"version":"build-2803163510"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100020230","name":"Jilin Provincial Health Commission","doi-asserted-by":"crossref","award":["10, 000RMB"],"award-info":[{"award-number":["10, 000RMB"]}],"id":[{"id":"10.13039\/501100020230","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The emergence of low-level rifampicin (RIF) resistance in\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      poses a challenge to tuberculosis (TB) control, as it often leads to discordance between genotypic resistance detected by molecular assays (e.g., Xpert MTB\/RIF) and phenotypic susceptibility in conventional drug susceptibility testing (DST). In this study, we performed whole-genome sequencing (WGS) on 17 clinical isolates from Changchun, Northeast China, which exhibited such discordance. All isolates harbored functional borderline mutations in the\n                      <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                      RRDR region, predominantly\n                      <jats:italic toggle=\"yes\">Leu452Pro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Leu430Pro<\/jats:italic>\n                      (29% each), followed by\n                      <jats:italic toggle=\"yes\">His445Asn<\/jats:italic>\n                      (18%). RIF minimum inhibitory concentration (MIC) values ranged from \u22640.25 to 1.0 mg\/L, confirming low-level resistance. Notably, 53% (9\/17) of the isolates were co-resistant to fluoroquinolones and 24% (4\/17) to isoniazid (INH). According to WHO classification, 59% (10\/17) were pre-extensively drug-resistant TB (Pre-XDR-TB) or multidrug-resistant TB (MDR-TB). Phylogenetic analysis revealed that 94% (16\/17) belonged to the East Asian Beijing lineage (Lineage 2.2.1), with no evidence of recent local transmission. These findings underscore the complexity of low-level RIF resistance and its frequent association with broader drug resistance in a dominant lineage, highlighting the need for integrating MIC and WGS into diagnostic algorithms to guide appropriate treatment and surveillance.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The accurate detection of RIF resistance is critical for the management of TB, yet standard phenotypic methods often fail to identify strains with low-level resistance conferred by borderline\n                        <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                        mutations. This study provides the first genomic characterization of such discordant isolates in Northeast China, revealing a high prevalence of co-resistance to other key drugs and a strong association with the locally dominant Beijing lineage. The findings emphasize that reliance on phenotypic DST alone may lead to underestimation of drug resistance and inappropriate treatment, potentially contributing to the emergence and spread of Pre-XDR-TB and MDR-TB. Incorporating MIC determination and WGS into routine diagnostics could enhance detection, inform tailored therapy, and improve surveillance of these clinically significant strains.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00327-26","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:04:50Z","timestamp":1784639090000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Genomic insights into low-level rifampicin resistance mediated by borderline\n                    <i>rpoB<\/i>\n                    mutations in\n                    <i>Mycobacterium tuberculosis<\/i>\n                    : prevalence and phylogeny in Northeast China"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8985-9206","authenticated-orcid":true,"given":"Lingling","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]},{"id":[{"id":"https:\/\/ror.org\/013jjp941","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Basic Medical Sciences, Beihua University","place":["Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4311-1793","authenticated-orcid":false,"given":"Feng","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Changchun Infectious Disease Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2025. Global tuberculosis report 2025. World Health Organization. Available from: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2025"},{"key":"e_1_3_5_3_2","unstructured":"World Health Organization. 2021. Technical report on critical concentrations for drug susceptibility testing of isoniazid and the rifamycins (Rifampicin Rifabutin and Rifapentine). World Health Organization Geneva. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240017283"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3638-z"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00783-2021"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jctube.2021.100222"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz065"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210302"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01885-20"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02236-24"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcr2.366"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy883"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.956171"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-025-00807-6"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.21.0428"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.21.0564"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00418-24"},{"key":"e_1_3_5_18_2","unstructured":"World Health Organization. 2023. Catalogue of mutations in Mycobacterium Tuberculosis complex and their association with drug resistance 2nd Ed. World Health Organization. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240082410"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48401-z"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S358301"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01599-17"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00571-25"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02741-12"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02328-20"},{"key":"e_1_3_5_25_2","unstructured":"Organization WH. 2022. Optimized broth microdilution plate methodology for drug susceptibility testing of Mycobacterium tuberculosis complex. Organization WH Geneva. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240047419"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-021-00673-7"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112147-20191215-00827"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes13101849"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715849"},{"key":"e_1_3_5_30_2","unstructured":"World Health Organization. 2022. WHO consolidated guidelines on tuberculosis. module 4: treatment \u2013 drug-resistant tuberculosis treatment 2022 update. World Health Organization Geneva. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240063129"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315817"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407426"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00327-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.00327-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:10:09Z","timestamp":1788268209000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.00327-26"}},"subtitle":[],"editor":[{"given":"Ping","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":31,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1128\/spectrum.00327-26"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.00327-26","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00327-26"}}