{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T16:14:05Z","timestamp":1778516045079,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The growing burden of drug-resistant tuberculosis (TB) constitutes a major public health challenge. Ethionamide (ETH), a second-line anti-TB drug, plays an important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the molecular mechanisms underlying ETH resistance remain incompletely elucidated. Thus, this study aimed to evaluate the effects of mutations in ETH resistance-associated genes (\n                      <jats:italic>inhA<\/jats:italic>\n                      ,\n                      <jats:italic>ethA<\/jats:italic>\n                      ,\n                      <jats:italic>ethR<\/jats:italic>\n                      , and\n                      <jats:italic>mshA<\/jats:italic>\n                      ) on ETH resistance levels among\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      (MTB) isolates from China.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 137 MTB isolates from China were tested for ETH minimum inhibitory concentrations (MICs) pusing Sensititre\n                      <jats:sup>\u00ae<\/jats:sup>\n                      plates, and the sequences of four ETH resistance-associated genes were analyzed based on genomic and PCR sequencing data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results showed that 95.1% (39\/41 isolates) of ETH-resistant isolates harbored at least one mutation in these four ETH resistance-associated genes. Most mutations were found in the\n                      <jats:italic>inhA<\/jats:italic>\n                      and\n                      <jats:italic>ethA<\/jats:italic>\n                      (including 5\u2019 untranslated region). Mutations in\n                      <jats:italic>inhA<\/jats:italic>\n                      region were mainly concentrated at the -777C&amp;gt;T site, whereas those in the\n                      <jats:italic>ethA<\/jats:italic>\n                      region were relatively scattered. Notably, multiple mutations were common in high-level ETH-resistant strains and were significantly associated with high-level resistance (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.012). Furthermore, several novel single mutations in ETH-resistant strains, including\n                      <jats:italic>inhA<\/jats:italic>\n                      -100C&amp;gt;A,\n                      <jats:italic>ethA<\/jats:italic>\n                      -31G&amp;gt;A, and\n                      <jats:italic>mshA<\/jats:italic>\n                      Tyr155Ser, were detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Different individual mutations and multiple concurrent mutations in ETH resistance-associated genes are associated with varying levels of ETH resistance. These results broaden our understanding of the molecular characteristics of ETH resistance in China.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1725219","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T06:32:47Z","timestamp":1768545167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of mutations in multiple Ethionamide-resistance-associated genes among Mycobacterium tuberculosis clinical isolates from China"],"prefix":"10.3389","volume":"15","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang-long","family":"Bo","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma-chao","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-qiang","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Life Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-can","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-ting","family":"Fan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-qin","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Lin","family":"Wan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-li","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2022.107677","article-title":"Mutation in Eth A protein of Mycobacterium tuberculosis conferred drug tolerance against enthinoamide in Mycobacterium smegmatis mc(2)155","volume":"98","author":"Anand","year":"2022","journal-title":"Comput. 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