{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:01:14Z","timestamp":1791223274436,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2009,2]]},"DOI":"10.1038\/nm.1915","type":"journal-article","created":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T13:51:15Z","timestamp":1233496275000},"page":"211-214","source":"Crossref","is-referenced-by-count":312,"title":["A replication clock for Mycobacterium tuberculosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Wendy P","family":"Gill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada S","family":"Harik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly R","family":"Whiddon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiling P","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E","family":"Mittler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Sherman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,2,1]]},"reference":[{"key":"BFnm1915_CR1","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1128\/CMR.00060-05","volume":"19","author":"DF Warner","year":"2006","unstructured":"Warner, D.F. & Mizrahi, V. Tuberculosis chemotherapy: the influence of bacillary stress and damage response pathways on drug efficacy. Clin. Microbiol. Rev. 19, 558\u2013570 (2006).","journal-title":"Clin. Microbiol. Rev."},{"key":"BFnm1915_CR2","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1128\/AAC.00055-06","volume":"51","author":"SH Cho","year":"2007","unstructured":"Cho, S.H. et al. Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 51, 1380\u20131385 (2007).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnm1915_CR3","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1128\/AAC.49.6.2294-2301.2005","volume":"49","author":"AJ Lenaerts","year":"2005","unstructured":"Lenaerts, A.J. et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob. Agents Chemother. 49, 2294\u20132301 (2005).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnm1915_CR4","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/S0140-6736(03)14333-4","volume":"362","author":"TR Frieden","year":"2003","unstructured":"Frieden, T.R., Sterling, T.R., Munsiff, S.S., Watt, C.J. & Dye, C. Tuberculosis. Lancet 362, 887\u2013899 (2003).","journal-title":"Lancet"},{"key":"BFnm1915_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev.micro.55.1.139","volume":"55","author":"LG Wayne","year":"2001","unstructured":"Wayne, L.G. & Sohaskey, C.D. Nonreplicating persistence of Mycobacterium tuberculosis. Annu. Rev. Microbiol. 55, 139\u2013163 (2001).","journal-title":"Annu. Rev. Microbiol."},{"key":"BFnm1915_CR6","first-page":"415","volume":"100","author":"AD Harries","year":"2006","unstructured":"Harries, A.D. & Dye, C. Tuberculosis. Ann. Trop. Med. Parasitol. 100, 415\u2013431 (2006).","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"BFnm1915_CR7","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1086\/345862","volume":"187","author":"KN Lewis","year":"2003","unstructured":"Lewis, K.N. et al. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. J. Infect. Dis. 187, 117\u2013123 (2003).","journal-title":"J. Infect. Dis."},{"key":"BFnm1915_CR8","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.4049\/jimmunol.175.2.1107","volume":"175","author":"V Lazarevic","year":"2005","unstructured":"Lazarevic, V., Nolt, D. & Flynn, J.L. Long-term control of Mycobacterium tuberculosis infection is mediated by dynamic immune responses. J. Immunol. 175, 1107\u20131117 (2005).","journal-title":"J. Immunol."},{"key":"BFnm1915_CR9","first-page":"83","volume":"42","author":"RJM Rees","year":"1961","unstructured":"Rees, R.J.M. & Hart, P.D. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br. J. Exp. Pathol. 42, 83\u201388 (1961).","journal-title":"Br. J. Exp. Pathol."},{"key":"BFnm1915_CR10","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1128\/IAI.73.1.546-551.2005","volume":"73","author":"EJ Munoz-Elias","year":"2005","unstructured":"Munoz-Elias, E.J. et al. Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Infect. Immun. 73, 546\u2013551 (2005).","journal-title":"Infect. Immun."},{"key":"BFnm1915_CR11","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/ni1091","volume":"5","author":"CL Cosma","year":"2004","unstructured":"Cosma, C.L., Humbert, O. & Ramakrishnan, L. Superinfecting mycobacteria home to established tuberculous granulomas. Nat. Immunol. 5, 828\u2013835 (2004).","journal-title":"Nat. Immunol."},{"key":"BFnm1915_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.dci.2007.04.003","volume":"32","author":"AH Meijer","year":"2008","unstructured":"Meijer, A.H. et al. Identification and real-time imaging of a myc-expressing neutrophil population involved in inflammation and mycobacterial granuloma formation in zebrafish. Dev. Comp. Immunol. 32, 36\u201349 (2008).","journal-title":"Dev. Comp. Immunol."},{"key":"BFnm1915_CR13","doi-asserted-by":"publisher","first-page":"6108","DOI":"10.1128\/IAI.00887-06","volume":"74","author":"LE Swaim","year":"2006","unstructured":"Swaim, L.E. et al. Mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity. Infect. Immun. 74, 6108\u20136117 (2006).","journal-title":"Infect. Immun."},{"key":"BFnm1915_CR14","first-page":"827","volume":"119","author":"GW Comstock","year":"1979","unstructured":"Comstock, G.W., Baum, C. & Snider, D.E. Isoniazid prophylaxis among alaskan eskimos: a final report of the Bethel isoniazid studies. Am. Rev. Respir. Dis. 119, 827\u2013830 (1979).","journal-title":"Am. Rev. Respir. Dis."},{"key":"BFnm1915_CR15","doi-asserted-by":"crossref","unstructured":"American Thoracic Society & Centers for Disease Control and Prevention. Supplement\u2014American Thoracic Society Centers for Disease Control and Prevention Targeted tuberculin testing and treatment of latent tuberculosis infection. Am. J. Respir. Crit. Care Med. 161, S221\u2013S247 (2000).","DOI":"10.1164\/ajrccm.161.supplement_3.ats600"},{"key":"BFnm1915_CR16","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/35016103","volume":"405","author":"CK Stover","year":"2000","unstructured":"Stover, C.K. et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405, 962\u2013966 (2000).","journal-title":"Nature"},{"key":"BFnm1915_CR17","doi-asserted-by":"publisher","first-page":"181","DOI":"10.7883\/yoken1952.19.181","volume":"19","author":"K Kanai","year":"1966","unstructured":"Kanai, K. Experimental studies on host-parasite equilibrium in tuberculous infection, in relation to vaccination and chemotherapy. Jpn. J. Med. Sci. Biol. 19, 181\u2013199 (1966).","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"BFnm1915_CR18","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1093\/rheumatology\/keh567","volume":"44","author":"J Keane","year":"2005","unstructured":"Keane, J. TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxford) 44, 714\u2013720 (2005).","journal-title":"Rheumatology (Oxford)"},{"key":"BFnm1915_CR19","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1099\/00221287-146-2-297","volume":"146","author":"G Bachrach","year":"2000","unstructured":"Bachrach, G. et al. A new single-copy mycobacterial plasmid, pMF1, from Mycobacterium fortuitum which is compatible with the pAL5000 replicon. Microbiology 146, 297\u2013303 (2000).","journal-title":"Microbiology"},{"key":"BFnm1915_CR20","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1126\/science.7681219","volume":"259","author":"MM Zambrano","year":"1993","unstructured":"Zambrano, M.M., Siegele, D.A., Almiron, M., Tormo, A. & Kolter, R. Microbial competition: Escherichia coli mutants that take over stationary phase cultures. Science 259, 1757\u20131760 (1993).","journal-title":"Science"},{"key":"BFnm1915_CR21","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1128\/JB.181.1.270-283.1999","volume":"181","author":"MJ Smeulders","year":"1999","unstructured":"Smeulders, M.J., Keer, J., Speight, R.A. & Williams, H.D. Adaptation of Mycobacterium smegmatis to stationary phase. J. Bacteriol. 181, 270\u2013283 (1999).","journal-title":"J. Bacteriol."},{"key":"BFnm1915_CR22","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511802843","volume-title":"Bootstrap Methods and Their Application","author":"AC Davison","year":"1997","unstructured":"Davison, A.C. & Hinkley, D.V. Bootstrap Methods and Their Application, Chs. 2 and 4 (Cambridge University Press, Cambridge, 1997)."},{"key":"BFnm1915_CR23","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0962-8479(97)90016-2","volume":"78","author":"ER Rhoades","year":"1997","unstructured":"Rhoades, E.R., Frank, A.A. & Orme, I.M. Progression of chronic pulmonary tuberculosis in mice aerogenically infected with virulent Mycobacterium tuberculosis. Tuber. Lung Dis. 78, 57\u201366 (1997).","journal-title":"Tuber. Lung Dis."},{"key":"BFnm1915_CR24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1084\/jem.193.3.271","volume":"193","author":"T Mogues","year":"2001","unstructured":"Mogues, T., Goodrich, M.E., Ryan, L., LaCourse, R. & North, R.J. The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice. J. Exp. Med. 193, 271\u2013280 (2001).","journal-title":"J. Exp. Med."},{"key":"BFnm1915_CR25","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1086\/506454","volume":"194","author":"B Rivas-Santiago","year":"2006","unstructured":"Rivas-Santiago, B. et al. \u03b2-defensin gene expression during the course of experimental tuberculosis infection. J. Infect. Dis. 194, 697\u2013701 (2006).","journal-title":"J. Infect. Dis."},{"key":"BFnm1915_CR26","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1164\/rccm.200507-1047OC","volume":"172","author":"E Nuermberger","year":"2005","unstructured":"Nuermberger, E. et al. Rifapentine, moxifloxacin or DNA vaccine improves treatment of latent tuberculosis in a mouse model. Am. J. Respir. Crit. Care Med. 172, 1452\u20131456 (2005).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFnm1915_CR27","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/path.2055","volume":"210","author":"S Aly","year":"2006","unstructured":"Aly, S. et al. Oxygen status of lung granulomas in Mycobacterium tuberculosis\u2013infected mice. J. Pathol. 210, 298\u2013305 (2006).","journal-title":"J. Pathol."},{"key":"BFnm1915_CR28","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/j.1462-5822.2005.00612.x","volume":"8","author":"MC Tsai","year":"2006","unstructured":"Tsai, M.C. et al. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell. Microbiol. 8, 218\u2013232 (2006).","journal-title":"Cell. Microbiol."},{"key":"BFnm1915_CR29","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1128\/IAI.01515-07","volume":"76","author":"LE Via","year":"2008","unstructured":"Via, L.E. et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits and nonhuman primates. Infect. Immun. 76, 2333\u20132340 (2008).","journal-title":"Infect. Immun."},{"key":"BFnm1915_CR30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/j.1574-6968.1996.tb08563.x","volume":"145","author":"BJ Wards","year":"1996","unstructured":"Wards, B.J. & Collins, D.M. Electroporation at elevated temperatures substantially improves transformation efficiency of slow-growing mycobacteria. FEMS Microbiol. Lett. 145, 101\u2013105 (1996).","journal-title":"FEMS Microbiol. Lett."},{"key":"BFnm1915_CR31","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1046\/j.1365-2958.2003.03474.x","volume":"48","author":"HD Park","year":"2003","unstructured":"Park, H.D. et al. Rv3133c\/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol. Microbiol. 48, 833\u2013843 (2003).","journal-title":"Mol. Microbiol."},{"key":"BFnm1915_CR32","doi-asserted-by":"publisher","first-page":"e1502","DOI":"10.1371\/journal.pone.0001502","volume":"3","author":"TR Rustad","year":"2008","unstructured":"Rustad, T.R., Harrell, M.I., Liao, R. & Sherman, D.R. The enduring hypoxic response of Mycobacterium tuberculosis. PLoS ONE 3, e1502 (2008).","journal-title":"PLoS ONE"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.1915.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.1915","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.1915.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:23:09Z","timestamp":1684434189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.1915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,2]]}},"alternative-id":["BFnm1915"],"URL":"https:\/\/doi.org\/10.1038\/nm.1915","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2]]}}}