{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:53:08Z","timestamp":1787003588209,"version":"build-2736575974"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-85092-7","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T12:24:02Z","timestamp":1738067042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Valerie F. A.","family":"March","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Maghradze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakha","family":"Mchedlishvili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teona","family":"Avaliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusudan","family":"Aspindzelashvili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaza","family":"Avaliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maia","family":"Kipiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nestani","family":"Tukvadze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levan","family":"Jugheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"Bouaouina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Doetsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galo A.","family":"Goig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Gagneux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Borrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"85092_CR1","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","volume":"22","author":"WR Miller","year":"2024","unstructured":"Miller, W. R. & Arias, C. A. ESKAPE pathogens: Antimicrobial resistance, epidemiology, clinical impact and therapeutics. Nat. Rev. Microbiol. 22, 598\u2013616 (2024).","journal-title":"Nat. Rev. Microbiol."},{"key":"85092_CR2","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1016\/S0140-6736(24)00876-6","volume":"403","author":"IN Okeke","year":"2024","unstructured":"Okeke, I. N. et al. The scope of the antimicrobial resistance challenge. Lancet 403, 2426\u20132438 (2024).","journal-title":"Lancet"},{"key":"85092_CR3","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.cmi.2017.08.026","volume":"23","author":"O Dyar","year":"2017","unstructured":"Dyar, O., Huttner, B., Schouten, J. & Pulcini, C. What is antimicrobial stewardship?. Clin. Microbiol. Infect. 23, 793\u2013798 (2017).","journal-title":"Clin. Microbiol. Infect."},{"key":"85092_CR4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ejim.2022.01.029","volume":"99","author":"S Bassetti","year":"2022","unstructured":"Bassetti, S., Tschudin-Sutter, S., Egli, A. & Osthoff, M. Optimizing antibiotic therapies to reduce the risk of bacterial resistance. Eur. J. Intern. Med. 99, 7\u201312 (2022).","journal-title":"Eur. J. Intern. Med."},{"issue":"10","key":"85092_CR5","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/s41579-024-01076-4","volume":"22","author":"D Cocker","year":"2024","unstructured":"Cocker, D. et al. Healthcare as a driver, reservoir and amplifier of antimicrobial resistance: opportunities for interventions. Nat. Rev. Microbiol. 22(10), 636\u2013649 (2024).","journal-title":"Nat. Rev. Microbiol."},{"key":"85092_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103768","volume":"9","author":"HY Lee","year":"2014","unstructured":"Lee, H. Y. et al. Culture conversion rate at 2 months of treatment according to diagnostic methods among patients with culture-positive pulmonary tuberculosis. PloS one 9, e103768 (2014).","journal-title":"PloS one"},{"key":"85092_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108035","volume":"9","author":"DB Tierney","year":"2014","unstructured":"Tierney, D. B. et al. Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment. PloS one 9, e108035 (2014).","journal-title":"PloS one"},{"key":"85092_CR8","unstructured":"WHO. Global tuberculosis report 2023. (2023)."},{"key":"85092_CR9","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/S0025-7125(16)30188-2","volume":"77","author":"JH Bates","year":"1993","unstructured":"Bates, J. H. & Stead, W. W. The history of tuberculosis as a global epidemic. Med. Clin. North Am. 77, 1205\u20131217 (1993).","journal-title":"Med. Clin. North Am."},{"key":"85092_CR10","first-page":"1704","volume":"6","author":"G Naveen","year":"2012","unstructured":"Naveen, G. & PeeraPur, B. V. Comparison of the Lowenstein-Jensen medium, the Middlebrook 7H10 medium and MB\/BacT for the isolation of Mycobacterium tuberculosis (MTB) from clinical specimens. J. Clin. Diagn. Res. JCDR 6, 1704 (2012).","journal-title":"J. Clin. Diagn. Res. JCDR"},{"key":"85092_CR11","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00608-00621","author":"K Zainabadi","year":"2021","unstructured":"Zainabadi, K. et al. Characterization of differentially detectable Mycobacterium tuberculosis in the sputum of subjects with drug-sensitive or drug-resistant tuberculosis before and after two months of therapy. Antimicrob. Agents Chemother. https:\/\/doi.org\/10.1128\/aac.00608-00621 (2021).","journal-title":"Antimicrob. Agents Chemother."},{"key":"85092_CR12","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1128\/IAI.00404-15","volume":"83","author":"M Ayrapetyan","year":"2015","unstructured":"Ayrapetyan, M., Williams, T. C., Baxter, R. & Oliver, J. Viable but nonculturable and persister cells coexist stochastically and are induced by human serum. Infect. Immun. 83, 4194\u20134203 (2015).","journal-title":"Infect. Immun."},{"key":"85092_CR13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s11783-024-1795-4","volume":"18","author":"L Guo","year":"2024","unstructured":"Guo, L. et al. Occurrence of viable but non-culturable (VBNC) pathogenic bacteria in tap water of public places. Front. Environ. Sci. Eng. 18, 35 (2024).","journal-title":"Front. Environ. Sci. Eng."},{"key":"85092_CR14","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/1541-4337.12513","volume":"19","author":"K Dong","year":"2020","unstructured":"Dong, K. et al. Induction, detection, formation, and resuscitation of viable but non-culturable state microorganisms. Compr. Rev. Food Sci. Food Saf. 19, 149\u2013183 (2020).","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"85092_CR15","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.5588\/ijtld.13.0063","volume":"17","author":"C Bark","year":"2013","unstructured":"Bark, C. et al. Comparison of time to positive and colony counting in an early bactericidal activity study of anti-tuberculosis treatment. Int. J. Tuberc. Lung Dis. 17, 1448\u20131451 (2013).","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"85092_CR16","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/jac\/dku415","volume":"70","author":"R Bowness","year":"2015","unstructured":"Bowness, R. et al. The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations. J. Antimicrob. Chemother. 70, 448\u2013455 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"85092_CR17","doi-asserted-by":"publisher","first-page":"6493","DOI":"10.1038\/s41598-021-86054-z","volume":"11","author":"BG Gordhan","year":"2021","unstructured":"Gordhan, B. G. et al. Detection of differentially culturable tubercle bacteria in sputum using mycobacterial culture filtrates. Sci. Rep. 11, 6493 (2021).","journal-title":"Sci. Rep."},{"key":"85092_CR18","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02192-02118","author":"K McAulay","year":"2018","unstructured":"McAulay, K. et al. Differentially detectable Mycobacterium tuberculosis cells in sputum from treatment-naive subjects in Haiti and their proportionate increase after initiation of treatment. MBio https:\/\/doi.org\/10.1128\/mbio.02192-02118 (2018).","journal-title":"MBio"},{"key":"85092_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119301","volume":"274","author":"A Chauhan","year":"2021","unstructured":"Chauhan, A., Kumar, M., Kumar, A. & Kanchan, K. Comprehensive review on mechanism of action, resistance and evolution of antimycobacterial drugs. Life Sci. 274, 119301 (2021).","journal-title":"Life Sci."},{"key":"85092_CR20","doi-asserted-by":"publisher","first-page":"6227","DOI":"10.1128\/aac.00518-16","volume":"60","author":"J Loraine","year":"2016","unstructured":"Loraine, J., Pu, F., Turapov, O. & Mukamolova, G. V. Development of an in vitro assay for detection of drug-induced resuscitation-promoting-factor-dependent mycobacteria. Antimicrob. Agents Chemother. 60, 6227\u20136233. https:\/\/doi.org\/10.1128\/aac.00518-16 (2016).","journal-title":"Antimicrob. Agents Chemother."},{"key":"85092_CR21","doi-asserted-by":"publisher","first-page":"E4832","DOI":"10.1073\/pnas.1705385114","volume":"114","author":"K Saito","year":"2017","unstructured":"Saito, K. et al. Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations. Proc. Natl. Acad. Sci. 114, E4832\u2013E4840 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"85092_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214088","volume":"14","author":"S Borrell","year":"2019","unstructured":"Borrell, S. et al. Reference set of Mycobacterium tuberculosis clinical strains: A tool for research and product development. PLoS one 14, e0214088 (2019).","journal-title":"PLoS one"},{"key":"85092_CR23","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1126\/scitranslmed.abg2612","volume":"13","author":"K Saito","year":"2021","unstructured":"Saito, K. et al. Oxidative damage and delayed replication allow viable Mycobacterium tuberculosis to go undetected. Sci. Trans. Med. 13, 2612 (2021).","journal-title":"Sci. Trans. Med."},{"key":"85092_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12879-018-3213-7","volume":"18","author":"ND Walter","year":"2018","unstructured":"Walter, N. D. et al. Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum. BMC Infect. Dis. 18, 1\u20137 (2018).","journal-title":"BMC Infect. Dis."},{"key":"85092_CR25","doi-asserted-by":"publisher","first-page":"e01601","DOI":"10.1128\/aac.01601-23","volume":"68","author":"KF Walsh","year":"2024","unstructured":"Walsh, K. F. et al. High variance in quantification of Mycobacterium tuberculosis at low bacterial loads and with differentially detectable mycobacteria. Antimicrob. Agents Chemother. 68, e01601-01623 (2024).","journal-title":"Antimicrob. Agents Chemother."},{"key":"85092_CR26","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.3389\/fmicb.2019.02381","volume":"10","author":"A Dusthackeer","year":"2019","unstructured":"Dusthackeer, A. et al. Differential culturability of mycobacterium tuberculosis in culture-negative sputum of patients with pulmonary tuberculosis and in a simulated model of dormancy. Front. Microbiol. 10, 2381. https:\/\/doi.org\/10.3389\/fmicb.2019.02381 (2019).","journal-title":"Front. Microbiol."},{"key":"85092_CR27","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00249-00218","author":"M Ayrapetyan","year":"2018","unstructured":"Ayrapetyan, M., Williams, T. & Oliver, J. D. Relationship between the viable but nonculturable state and antibiotic persister cells. J. Bacteriol. https:\/\/doi.org\/10.1128\/jb.00249-00218 (2018).","journal-title":"J. Bacteriol."},{"key":"85092_CR28","doi-asserted-by":"publisher","first-page":"1064148","DOI":"10.3389\/fcimb.2022.1064148","volume":"12","author":"JS Peters","year":"2023","unstructured":"Peters, J. S. et al. Differentially culturable tubercle bacteria as a measure of tuberculosis treatment response. Front. Cell. Infect. Microbiol. 12, 1064148 (2023).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"85092_CR29","doi-asserted-by":"publisher","first-page":"fuae006","DOI":"10.1093\/femsre\/fuae006","volume":"48","author":"M Orgeur","year":"2024","unstructured":"Orgeur, M., Sous, C., Madacki, J. & Brosch, R. Evolution and emergence of Mycobacterium tuberculosis. FEMS Microbiol. Rev. 48, fuae006 (2024).","journal-title":"FEMS Microbiol. Rev."},{"key":"85092_CR30","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1038\/s41467-023-37719-y","volume":"14","author":"C Loiseau","year":"2023","unstructured":"Loiseau, C. et al. The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot. Nat. Commun. 14, 1988. https:\/\/doi.org\/10.1038\/s41467-023-37719-y (2023).","journal-title":"Nat. Commun."},{"key":"85092_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2024.116275","volume":"109","author":"MAM Ferreira","year":"2024","unstructured":"Ferreira, M. A. M., Dos Santos, L. C., Castellani, L. G. S., Brunetti, M. N. & Palaci, M. Application of BactTiter-Glo ATP bioluminescence assay for Mycobacterium tuberculosis detection. Diagn. Microbiol. Infect. Dis. 109, 116275 (2024).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"85092_CR32","first-page":"8","volume":"98","author":"A Yuroff","year":"2008","unstructured":"Yuroff, A., Fan, F., Butler, B. & Collins, M. Application of the BacTiter-Glo\u2122 assay for rapid enumeration and screening of antimicrobial compounds for Mycobacterium avium complex bacteria. Promega Notes 98, 8\u201310 (2008).","journal-title":"Promega Notes"},{"key":"85092_CR33","first-page":"111","volume":"78","author":"A Pital","year":"1958","unstructured":"Pital, A. A rapid method for determining the drug susceptibility of Mycobacterium tuberculosis. Am. Rev. Tuberc. Pulm. Dis. 78, 111\u2013116 (1958).","journal-title":"Am. Rev. Tuberc. Pulm. Dis."},{"key":"85092_CR34","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00176-00116","author":"I Bartek","year":"2016","unstructured":"Bartek, I. et al. Antibiotic bactericidal activity is countered by maintaining pH homeostasis in Mycobacterium smegmatis. Msphere https:\/\/doi.org\/10.1128\/msphere.00176-00116 (2016).","journal-title":"Msphere"},{"key":"85092_CR35","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1111\/1462-2920.14075","volume":"20","author":"JS Kim","year":"2018","unstructured":"Kim, J. S., Chowdhury, N., Yamasaki, R. & Wood, T. K. Viable but non-culturable and persistence describe the same bacterial stress state. Environ. Microbiol. 20, 2038\u20132048 (2018).","journal-title":"Environ. Microbiol."},{"key":"85092_CR36","first-page":"93","volume":"43","author":"D Oliver James","year":"2005","unstructured":"Oliver James, D. The viable but nonculturable state in bacteria. J. Microbiol. 43, 93\u2013100 (2005).","journal-title":"J. Microbiol."},{"key":"85092_CR37","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jare.2023.08.002","volume":"60","author":"D Yang","year":"2024","unstructured":"Yang, D., Wang, W., Zhao, L., Rao, L. & Liao, X. Resuscitation of viable but nonculturable bacteria promoted by ATP-mediated NAD+ synthesis. J. Adv. Res. 60, 27\u201339 (2024).","journal-title":"J. Adv. Res."},{"key":"85092_CR38","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/907170","volume":"2013","author":"B Zeng","year":"2013","unstructured":"Zeng, B. et al. Formation and resuscitation of viable but nonculturable Salmonella typhi. BioMed Res. Int. 2013, 907170 (2013).","journal-title":"BioMed Res. Int."},{"key":"85092_CR39","first-page":"e01185","volume":"68","author":"H Poonawala","year":"2024","unstructured":"Poonawala, H. et al. Transcriptomic responses to antibiotic exposure in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 68, e01185-e1123 (2024).","journal-title":"Antimicrob. Agents Chemother."},{"key":"85092_CR40","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1093\/jac\/dkt086","volume":"68","author":"S Pasquaroli","year":"2013","unstructured":"Pasquaroli, S. et al. Antibiotic pressure can induce the viable but non-culturable state in Staphylococcus aureus growing in biofilms. J. Antimicrob. Chemother. 68, 1812\u20131817 (2013).","journal-title":"J. Antimicrob. Chemother."},{"key":"85092_CR41","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1093\/jac\/dkt357","volume":"69","author":"J Dhillon","year":"2014","unstructured":"Dhillon, J., Fourie, P. B. & Mitchison, D. A. Persister populations of Mycobacterium tuberculosis in sputum that grow in liquid but not on solid culture media. J. Antimicrob. Chemother. 69, 437\u2013440 (2014).","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-85092-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-85092-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-85092-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T23:43:31Z","timestamp":1738107811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-85092-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["85092"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-85092-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"assertion":[{"value":"29 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3588"}}