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Although present in all <jats:italic>Mycobacterium sp<\/jats:italic>., ESX\u20103 remains to be elucidated in <jats:italic>Mycobacterium abscessus<\/jats:italic>. In the study reported here, impaired ESX\u20103 seriously restricts the growth of <jats:italic>M. abscesses<\/jats:italic> under iron\u2010limited conditions; growth is salvaged by functional ESX\u20103 or iron supplementation. Notably, impaired ESX\u20103 does not kill <jats:italic>M. abscesses<\/jats:italic> when environmental iron is insufficient but induces persistence to bedaquiline, a diarylquinoline class antibiotic used to treat multidrug\u2010resistant mycobacteria. One potential mechanism contributing to persistence is the iron deficiency due to impaired ESX\u20103 suppressing succinate dehydrogenase activity, which dysregulates the tricarboxylic acid cycle and inactivates bedaquiline. Experiments conducted here also demonstrate that the regulator, MtrA, can bind ESX\u20103 and promote the survival of <jats:italic>M. abscessus<\/jats:italic>. As such, this study suggests that a novel pathway involving MtrA, ESX\u20103, iron metabolism, and the TCA cycle contributes to bedaquiline persistence in <jats:italic>M. abscesses<\/jats:italic> growing under iron\u2010limited conditions.<\/jats:p>","DOI":"10.1002\/smtd.202300183","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T04:04:43Z","timestamp":1686283483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impaired ESX\u20103 Induces Bedaquiline Persistence in <i>Mycobacterium abscessus<\/i> Growing Under Iron\u2010Limited Conditions"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-044X","authenticated-orcid":false,"given":"Bing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhili","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junsheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhemin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-7295","authenticated-orcid":false,"given":"Haiqing","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"},{"name":"School of Medicine Tongji University  Shanghai 200092 China"},{"name":"Shanghai Key Laboratory of Tuberculosis Shanghai Pulmonary Hospital School of Medicine Tongji University  Shanghai 200433 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00285"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.842858"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c06501"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00535"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523321113"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01073-14"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2018.06.010"},{"key":"e_1_2_9_8_1","first-page":"235","volume":"404","author":"Bottai D.","year":"2017","journal-title":"Curr. 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