{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T17:38:52Z","timestamp":1770313132888,"version":"3.49.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82202568"],"award-info":[{"award-number":["82202568"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Sailing Program","award":["22YF1445700"],"award-info":[{"award-number":["22YF1445700"]}]},{"DOI":"10.13039\/501100017577","name":"Basic Public Welfare Research Program of Zhejiang Province","doi-asserted-by":"crossref","award":["LGF20H010003"],"award-info":[{"award-number":["LGF20H010003"]}],"id":[{"id":"10.13039\/501100017577","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shangda Translational Medicine Foundation of Wenzhou Research Institute of Shanghai University","award":["SDTMF2022EP02"],"award-info":[{"award-number":["SDTMF2022EP02"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"DOI":"10.1186\/s12866-025-04388-4","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:32:34Z","timestamp":1766122354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current drug susceptibility testing in the L\u00f6wenstein-Jensen medium leads to underestimating of prothionamide resistance in multi-drug resistant Mycobacterium tuberculosis"],"prefix":"10.1186","volume":"26","author":[{"given":"Xinchang","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiqing","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siran","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiazhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"4388_CR1","volume-title":"Global tuberculosis report 2022","author":"World Health Organization","year":"2022","unstructured":"World Health Organization. Global tuberculosis report 2022. Geneva, Switzerland: World Health Organization; 2022."},{"key":"4388_CR2","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1086\/653115","volume":"51","author":"KR Jacobson","year":"2010","unstructured":"Jacobson KR, Tierney DB, Jeon CY, Mitnick CD, Murray MB. Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis. 2010;51:6\u201314. https:\/\/doi.org\/10.1086\/653115.","journal-title":"Clin Infect Dis"},{"key":"4388_CR3","doi-asserted-by":"publisher","first-page":"e1001300","DOI":"10.1371\/journal.pmed.1001300","volume":"9","author":"SD Ahuja","year":"2012","unstructured":"Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, Bayona JN, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med. 2012;9:e1001300. https:\/\/doi.org\/10.1371\/journal.pmed.1001300.","journal-title":"PLoS Med"},{"key":"4388_CR4","doi-asserted-by":"publisher","first-page":"3799","DOI":"10.1128\/AAC.47.12.3799-3805.2003","volume":"47","author":"GP Morlock","year":"2003","unstructured":"Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC, ethA. inhA, and KatG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2003;47:3799\u2013805. https:\/\/doi.org\/10.1128\/AAC.47.12.3799-3805.2003.","journal-title":"Antimicrob Agents Chemother"},{"key":"4388_CR5","doi-asserted-by":"publisher","first-page":"e265","DOI":"10.1016\/S2666-5247(21)00301-3","volume":"3","author":"TM Walker","year":"2022","unstructured":"Walker TM, Miotto P, Koser CU, Fowler PW, Knaggs J, Iqbal Z, et al. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis. Lancet Microbe. 2022;3:e265\u201373. https:\/\/doi.org\/10.1016\/S2666-5247(21)00301-3.","journal-title":"Lancet Microbe"},{"key":"4388_CR6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1126\/science.8284673","volume":"263","author":"A Banerjee","year":"1994","unstructured":"Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, et al. InhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994;263:227\u201330. https:\/\/doi.org\/10.1126\/science.8284673.","journal-title":"Science"},{"key":"4388_CR7","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/1471-2334-13-432","volume":"13","author":"SG Mpagama","year":"2013","unstructured":"Mpagama SG, Houpt ER, Stroup S, Kumburu H, Gratz J, Kibiki GS, et al. Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania. BMC Infect Dis. 2013;13:432. https:\/\/doi.org\/10.1186\/1471-2334-13-432.","journal-title":"BMC Infect Dis"},{"key":"4388_CR8","doi-asserted-by":"publisher","first-page":"961","DOI":"10.5588\/ijtld.13.0197","volume":"18","author":"A Chaiprasert","year":"2014","unstructured":"Chaiprasert A, Srimuang S, Tingtoy N, Makhao N, Sirirudeeporn P, Tomnongdee N, et al. Second-line drug susceptibilities of multidrug-resistant tuberculosis strains isolated in thailand: an update. Int J Tuberc Lung Dis. 2014;18:961\u20133. https:\/\/doi.org\/10.5588\/ijtld.13.0197.","journal-title":"Int J Tuberc Lung Dis"},{"key":"4388_CR9","doi-asserted-by":"publisher","first-page":"655","DOI":"10.5588\/ijtld.13.0516","volume":"18","author":"F Salvo","year":"2014","unstructured":"Salvo F, Dorjee K, Dierberg K, Cronin W, Sadutshang TD, Migliori GB, et al. Survey of tuberculosis drug resistance among Tibetan refugees in India. Int J Tuberc Lung Dis. 2014;18:655\u201362. https:\/\/doi.org\/10.5588\/ijtld.13.0516.","journal-title":"Int J Tuberc Lung Dis"},{"key":"4388_CR10","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1093\/jac\/dku438","volume":"70","author":"E Cambau","year":"2015","unstructured":"Cambau E, Viveiros M, Machado D, Raskine L, Ritter C, Tortoli E, et al. Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study. J Antimicrob Chemother. 2015;70:686\u201396. https:\/\/doi.org\/10.1093\/jac\/dku438.","journal-title":"J Antimicrob Chemother"},{"key":"4388_CR11","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.3389\/fmicb.2017.02358","volume":"8","author":"Y Tan","year":"2017","unstructured":"Tan Y, Su B, Zheng H, Song Y, Wang Y, Pang Y. Molecular characterization of prothionamide-resistant Mycobacterium tuberculosis isolates in Southern China. Front Microbiol. 2017;8:2358. https:\/\/doi.org\/10.3389\/fmicb.2017.02358.","journal-title":"Front Microbiol"},{"key":"4388_CR12","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2147\/IDR.S268799","volume":"14","author":"Y Song","year":"2021","unstructured":"Song Y, Wang G, Li Q, Liu R, Ma L, Li Q, et al. The value of the InhA mutation detection in predicting ethionamide resistance using melting curve technology. Infect Drug Resist. 2021;14:329\u201334. https:\/\/doi.org\/10.2147\/IDR.S268799.","journal-title":"Infect Drug Resist"},{"key":"4388_CR13","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1089\/mdr.2014.0094","volume":"21","author":"N Li","year":"2015","unstructured":"Li N, Liao X, Chen L, Wang J, Liu M, Zhang H. Antibiotic susceptibility patterns of Mycobacterium tuberculosis isolates from Guizhou Province of China against 13 antituberculosis drugs. Microb Drug Resist. 2015;21:292\u20136. https:\/\/doi.org\/10.1089\/mdr.2014.0094.","journal-title":"Microb Drug Resist"},{"key":"4388_CR14","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.jmii.2015.04.003","volume":"49","author":"Z Baku\u0142a","year":"2016","unstructured":"Baku\u0142a Z, Napi\u00f3rkowska A, Kami\u0144ski M, Augustynowicz-Kope\u0107 E, Zwolska Z, Bielecki J, et al. Second-line anti-tuberculosis drug resistance and its genetic determinants in multidrug-resistant Mycobacterium tuberculosis clinical isolates. J Microbiol Immunol Infect. 2016;49:439\u201344. https:\/\/doi.org\/10.1016\/j.jmii.2015.04.003.","journal-title":"J Microbiol Immunol Infect"},{"key":"4388_CR15","doi-asserted-by":"publisher","unstructured":"Hu Y, Xu L, He YL, Pang Y, Lu N, Liu J, et al. Prevalence and molecular characterization of Second-Line drugs resistance among Multidrug-Resistant Mycobacterium tuberculosis isolates in Southwest of China. Biomed Res Int 2017. 2017;4563826. https:\/\/doi.org\/10.1155\/2017\/4563826.","DOI":"10.1155\/2017\/4563826"},{"key":"4388_CR16","doi-asserted-by":"publisher","first-page":"956171","DOI":"10.3389\/fpubh.2022.956171","volume":"10","author":"Y Che","year":"2022","unstructured":"Che Y, Lin Y, Yang T, Chen T, Sang G, Chen Q, et al. Evaluation of whole-genome sequence to predict drug resistance of nine anti-tuberculosis drugs and characterize resistance genes in clinical rifampicin-resistant Mycobacterium tuberculosis isolates from Ningbo, China. Front Public Health. 2022;10:956171. https:\/\/doi.org\/10.3389\/fpubh.2022.956171.","journal-title":"Front Public Health"},{"key":"4388_CR17","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1128\/JCM.44.3.688-692.2006","volume":"44","author":"S Rusch-Gerdes","year":"2006","unstructured":"Rusch-Gerdes S, Pfyffer GE, Casal M, Chadwick M, Siddiqi S. Multicenter laboratory validation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials. J Clin Microbiol. 2006;44:688\u201392. https:\/\/doi.org\/10.1128\/JCM.44.3.688-692.2006.","journal-title":"J Clin Microbiol"},{"key":"4388_CR18","unstructured":"World Health Organization. 2018. Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. World Health Organization, Geneva, Switzerland."},{"key":"4388_CR19","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/s0041-3879(66)80003-x","volume":"47","author":"MJ Lefford","year":"1966","unstructured":"Lefford MJ, Mitchison DA. Comparison of methods for testing the sensitivity of Mycobacterium tuberculosis to ethionamide. Tubercle. 1966;47:250\u201361. https:\/\/doi.org\/10.1016\/s0041-3879(66)80003-x.","journal-title":"Tubercle"},{"key":"4388_CR20","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1128\/AAC.01030-10","volume":"55","author":"F Brossier","year":"2011","unstructured":"Brossier F, Veziris N, Truffot-Pernot C, Jarlier V, Sougakoff W. Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2011;55:355\u201360. https:\/\/doi.org\/10.1128\/AAC.01030-10.","journal-title":"Antimicrob Agents Chemother"},{"key":"4388_CR21","doi-asserted-by":"publisher","first-page":"7805","DOI":"10.1128\/aac.01028-15","volume":"59","author":"J Rueda","year":"2015","unstructured":"Rueda J, Realpe T, Mejia GI, Zapata E, Rozo JC, Ferro BE, et al. Genotypic analysis of genes associated with independent resistance and cross-resistance to isoniazid and ethionamide in Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother. 2015;59:7805\u201310. https:\/\/doi.org\/10.1128\/aac.01028-15.","journal-title":"Antimicrob Agents Chemother"},{"key":"4388_CR22","doi-asserted-by":"publisher","first-page":"502","DOI":"10.5588\/ijtld.10.0238","volume":"15","author":"T Sch\u00f6n","year":"2011","unstructured":"Sch\u00f6n T, Jur\u00e9en P, Chryssanthou E, Giske CG, Stureg\u00e5rd E, Kahlmeter G, et al. Wild-type distributions of seven oral second-line drugs against Mycobacterium tuberculosis. Int J Tuberc Lung Dis. 2011;15:502\u20139. https:\/\/doi.org\/10.5588\/ijtld.10.0238.","journal-title":"Int J Tuberc Lung Dis"},{"key":"4388_CR23","doi-asserted-by":"publisher","first-page":"e265","DOI":"10.1016\/s2666-5247(21)00301-3","volume":"3","author":"TM Walker","year":"2022","unstructured":"Walker TM, Miotto P, K\u00f6ser CU, Fowler PW, Knaggs J, Iqbal Z, et al. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis. Lancet Microbe. 2022;3:e265\u201373. https:\/\/doi.org\/10.1016\/s2666-5247(21)00301-3.","journal-title":"Lancet Microbe"},{"key":"4388_CR24","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.3389\/fmicb.2019.01741","volume":"10","author":"X Chen","year":"2019","unstructured":"Chen X, He G, Wang S, Lin S, Chen J, Zhang W. Evaluation of whole-genome sequence method to diagnose resistance of 13 anti-tuberculosis drugs and characterize resistance genes in clinical multi-drug resistance Mycobacterium tuberculosis isolates from China. Front Microbiol. 2019;10:1741. https:\/\/doi.org\/10.3389\/fmicb.2019.01741.","journal-title":"Front Microbiol"},{"key":"4388_CR25","doi-asserted-by":"publisher","unstructured":"Gomes LC, Campino S, Marinho CRF, Clark TG, Phelan JE. Whole genome sequencing reveals large deletions and other loss of function mutations in Mycobacterium tuberculosis drug resistance genes. Microb Genom. 2021;7. https:\/\/doi.org\/10.1099\/mgen.0.000724.","DOI":"10.1099\/mgen.0.000724"},{"key":"4388_CR26","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1038\/s41467-023-37719-y","volume":"14","author":"C Loiseau","year":"2023","unstructured":"Loiseau C, Windels EM, Gygli SM, Jugheli L, Maghradze N, Brites D, et al. The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot. Nat Commun. 2023;14:1988. https:\/\/doi.org\/10.1038\/s41467-023-37719-y.","journal-title":"Nat Commun"},{"key":"4388_CR27","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.tube.2016.09.028","volume":"101","author":"F Brossier","year":"2016","unstructured":"Brossier F, Cambau E, Tessier E, Jarlier V, Sougakoff W. The in vitro mechanisms of Isoniazid and ethionamide resistance poorly reflect those in vivo in Mycobacterium tuberculosis. Tuberculosis (Edinb). 2016;101:144\u20135. https:\/\/doi.org\/10.1016\/j.tube.2016.09.028.","journal-title":"Tuberculosis (Edinb)"},{"key":"4388_CR28","doi-asserted-by":"publisher","first-page":"e0207323","DOI":"10.1128\/mbio.02073-23","volume":"15","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Wang S, Chen X, Cui P, Chen J, Zhang W. Mutations in the promoter region of methionine transporter gene MetM (Rv3253c) confer para-aminosalicylic acid (PAS) resistance in Mycobacterium tuberculosis. mBio. 2024;15:e0207323. https:\/\/doi.org\/10.1128\/mbio.02073-23.","journal-title":"mBio"},{"key":"4388_CR29","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00616-19","author":"ND Hicks","year":"2019","unstructured":"Hicks ND, Carey AF, Yang J, Zhao Y, Fortune SM. Bacterial genome-wide association identifies novel factors that contribute to ethionamide and prothionamide susceptibility in Mycobacterium tuberculosis. mBio. 2019. https:\/\/doi.org\/10.1128\/mBio.00616-19.","journal-title":"mBio"},{"key":"4388_CR30","doi-asserted-by":"publisher","first-page":"e10411041","DOI":"10.1016\/j.cmi.2018.12.008","volume":"25","author":"MM Islam","year":"2019","unstructured":"Islam MM, Tan Y, Hameed HMA, Liu Z, Chhotaray C, Liu Y, et al. Detection of novel mutations associated with independent resistance and cross-resistance to Isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates. Clin Microbiol Infect. 2019;25:e10411041\u20137. https:\/\/doi.org\/10.1016\/j.cmi.2018.12.008.","journal-title":"Clin Microbiol Infect"},{"key":"4388_CR31","doi-asserted-by":"publisher","first-page":"e0251621","DOI":"10.1128\/spectrum.02516-21","volume":"10","author":"X Wu","year":"2022","unstructured":"Wu X, Tan G, Sha W, Liu H, Yang J, Guo Y, et al. Use of Whole-Genome sequencing to predict Mycobacterium tuberculosis complex drug resistance from early positive liquid cultures. Microbiol Spectr. 2022;10:e0251621. https:\/\/doi.org\/10.1128\/spectrum.02516-21.","journal-title":"Microbiol Spectr"},{"key":"4388_CR32","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/s1473-3099(21)00452-7","volume":"22","author":"A Penn-Nicholson","year":"2022","unstructured":"Penn-Nicholson A, Georghiou SB, Ciobanu N, Kazi M, Bhalla M, David A, et al. Detection of isoniazid, fluoroquinolone, ethionamide, amikacin, kanamycin, and capreomycin resistance by the Xpert MTB\/XDR assay: a cross-sectional multicentre diagnostic accuracy study. Lancet Infect Dis. 2022;22:242\u20139. https:\/\/doi.org\/10.1016\/s1473-3099(21)00452-7.","journal-title":"Lancet Infect Dis"},{"key":"4388_CR33","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/s41564-018-0218-3","volume":"3","author":"ND Hicks","year":"2018","unstructured":"Hicks ND, Yang J, Zhang X, Zhao B, Grad YH, Liu L, et al. Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance. Nat Microbiol. 2018;3:1032\u201342. https:\/\/doi.org\/10.1038\/s41564-018-0218-3.","journal-title":"Nat Microbiol"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-025-04388-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-025-04388-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-025-04388-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T03:18:44Z","timestamp":1770261524000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12866-025-04388-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4388"],"URL":"https:\/\/doi.org\/10.1186\/s12866-025-04388-4","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"assertion":[{"value":"4 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study used pre-banked clinical isolates without any associated patient-identifiable information. The isolate collection protocols were approved by the ethics committee of Huashan Hospital affiliated to Fudan University (KY2018-291). The study was conducted in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"88"}}