{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T04:25:18Z","timestamp":1767155118916},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Regardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5\u2009million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill <jats:italic>Mtb<\/jats:italic> by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of <jats:italic>Mtb<\/jats:italic> and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in <jats:italic>Mtb<\/jats:italic> infected animals. The mechanism involved was through enhancement of IFN-\u03b3<jats:sup>+<\/jats:sup>TNF-\u03b1<jats:sup>+<\/jats:sup> polyfunctional Th1 cells and IL-17A<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup> Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against <jats:italic>Mtb<\/jats:italic>. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.<\/jats:p>","DOI":"10.1038\/srep23917","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T09:19:28Z","timestamp":1460020768000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host"],"prefix":"10.1038","volume":"6","author":[{"given":"Pradeep K","family":"Rai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sathi Babu","family":"Chodisetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajid","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudeep K","family":"Maurya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uthaman","family":"Gowthaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguang","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok K","family":"Janmeja","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javed N","family":"Agrewala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"BFsrep23917_CR1","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1038\/sj.gt.3302465","volume":"12","author":"SJ Ha","year":"2005","unstructured":"Ha, S. J. et al. Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis. Gene therapy 12, 634\u2013638 (2005).","journal-title":"Gene therapy"},{"key":"BFsrep23917_CR2","doi-asserted-by":"publisher","first-page":"e384","DOI":"10.1371\/journal.pmed.0030384","volume":"3","author":"H Cox","year":"2006","unstructured":"Cox, H. et al. Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance. Plos Med. 3, e384 (2006).","journal-title":"Plos Med."},{"key":"BFsrep23917_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1046\/j.1365-3156.2003.01156.x","volume":"9","author":"RJ Coker","year":"2004","unstructured":"Coker, R. J. Review: multidrug-resistant tuberculosis: public health challenges. Tropical medicine & international health: TM & IH 9, 25\u201340 (2004).","journal-title":"Tropical medicine & international health: TM & IH"},{"key":"BFsrep23917_CR4","first-page":"657","volume":"4","author":"DS ElFeky","year":"2015","unstructured":"ElFeky, D. S. & ElShimy, A. Evaluation of the Diagnostic Performance of Anyplex II MTB\/MDR\/XDR Detection Assay for Detection and Antimicrobial Susceptibility testing of Mycobacterium tuberculosis from Sputum Specimens. Int. J. Curr. Microbiol. App. Sci 4, 657\u2013669 (2015).","journal-title":"Int. J. Curr. Microbiol. App. Sci"},{"key":"BFsrep23917_CR5","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1126\/science.1063814","volume":"295","author":"C Dye","year":"2002","unstructured":"Dye, C., Williams, B. G., Espinal, M. A. & Raviglione, M. C. Erasing the world\u2019s slow stain: strategies to beat multidrug-resistant tuberculosis. Science 295, 2042\u20132046 (2002).","journal-title":"Science"},{"key":"BFsrep23917_CR6","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1590\/S1806-37132010000500016","volume":"36","author":"MA Arbex","year":"2010","unstructured":"Arbex, M. A., Varella Mde, C., Siqueira, H. R. & Mello, F. A. Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs. Jornal brasileiro de pneumologia: publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia 36, 626\u2013640 (2010).","journal-title":"Jornal brasileiro de pneumologia: publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia"},{"key":"BFsrep23917_CR7","doi-asserted-by":"publisher","first-page":"e16097","DOI":"10.1371\/journal.pone.0016097","volume":"6","author":"V Singh","year":"2011","unstructured":"Singh, V. et al. Co-administration of IL\u2009\u2212\u20091\u2009+\u2009IL\u2009\u2212\u20096\u2009+\u2009TNF-alpha with Mycobacterium tuberculosis infected macrophages vaccine induces better protective T cell memory than BCG. Plos one 6, e16097 (2011).","journal-title":"Plos one"},{"key":"BFsrep23917_CR8","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1001\/jama.291.17.2086","volume":"291","author":"NE Aronson","year":"2004","unstructured":"Aronson, N. E. et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: a 60-year follow-up study. Jama 291, 2086\u20132091 (2004).","journal-title":"Jama"},{"key":"BFsrep23917_CR9","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.tube.2013.01.003","volume":"93","author":"M Tameris","year":"2013","unstructured":"Tameris, M. et al. Lessons learnt from the first efficacy trial of a new infant tuberculosis vaccine since BCG. Tuberculosis 93, 143\u2013149 (2013).","journal-title":"Tuberculosis"},{"key":"BFsrep23917_CR10","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0140-6736(13)60177-4","volume":"381","author":"MD Tameris","year":"2013","unstructured":"Tameris, M. D. et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. The Lancet 381, 1021\u20131028 (2013).","journal-title":"The Lancet"},{"key":"BFsrep23917_CR11","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/infdis\/jir548","volume":"204","author":"U Gowthaman","year":"2011","unstructured":"Gowthaman, U. et al. Promiscuous peptide of 16\u2009kDa antigen linked to Pam2Cys protects against Mycobacterium tuberculosis by evoking enduring memory T-cell response. The Journal of infectious diseases 204, 1328\u20131338 (2011).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep23917_CR12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/nrmicro2321","volume":"8","author":"CV Harding","year":"2010","unstructured":"Harding, C. V. & Boom, W. H. Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nature reviews. Microbiology 8, 296\u2013307 (2010).","journal-title":"Nature reviews. Microbiology"},{"key":"BFsrep23917_CR13","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/ni1449","volume":"8","author":"SA Khader","year":"2007","unstructured":"Khader, S. A. et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nature immunology 8, 369\u2013377 (2007).","journal-title":"Nature immunology"},{"key":"BFsrep23917_CR14","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.cyto.2007.11.022","volume":"41","author":"SA Khader","year":"2008","unstructured":"Khader, S. A. & Cooper, A. M. IL-23 and IL-17 in tuberculosis. Cytokine 41, 79\u201383 (2008).","journal-title":"Cytokine"},{"key":"BFsrep23917_CR15","doi-asserted-by":"publisher","first-page":"30190","DOI":"10.1074\/jbc.C114.598946","volume":"289","author":"S Tousif","year":"2014","unstructured":"Tousif, S. et al. Isoniazid induces apoptosis of activated CD4+ T cells: implications for post-therapy tuberculosis reactivation and reinfection. The Journal of biological chemistry 289, 30190\u201330195 (2014).","journal-title":"The Journal of biological chemistry"},{"key":"BFsrep23917_CR16","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","volume":"28","author":"J Zhu","year":"2010","unstructured":"Zhu, J., Yamane, H. & Paul, W. E. Differentiation of effector CD4 T cell populations. Annual review of immunology 28, 445 (2010).","journal-title":"Annual review of immunology"},{"key":"BFsrep23917_CR17","doi-asserted-by":"publisher","first-page":"4955","DOI":"10.4049\/jimmunol.181.7.4955","volume":"181","author":"EK Forbes","year":"2008","unstructured":"Forbes, E. K. et al. Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice. Journal of immunology 181, 4955\u20134964 (2008).","journal-title":"Journal of immunology"},{"key":"BFsrep23917_CR18","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1182\/blood-2010-10-312751","volume":"117","author":"S Dutt","year":"2011","unstructured":"Dutt, S. et al. CD8+ CD44hi but not CD4+ CD44hi memory T cells mediate potent graft antilymphoma activity without GVHD. Blood 117, 3230\u20133239 (2011).","journal-title":"Blood"},{"key":"BFsrep23917_CR19","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.4049\/jimmunol.0901427","volume":"184","author":"PG Thomas","year":"2010","unstructured":"Thomas, P. G. et al. Physiological numbers of CD4+ T cells generate weak recall responses following influenza virus challenge. The journal of immunology 184, 1721\u20131727 (2010).","journal-title":"The journal of immunology"},{"key":"BFsrep23917_CR20","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.immuni.2004.06.014","volume":"21","author":"L Ohl","year":"2004","unstructured":"Ohl, L. et al. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21, 279\u2013288 (2004).","journal-title":"Immunity"},{"key":"BFsrep23917_CR21","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1086\/653827","volume":"202","author":"V Singh","year":"2010","unstructured":"Singh, V. et al. Coadministration of interleukins 7 and 15 with bacille Calmette-Guerin mounts enduring T cell memory response against Mycobacterium tuberculosis. The Journal of infectious diseases 202, 480\u2013489 (2010).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep23917_CR22","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1093\/infdis\/jiu472","volume":"211","author":"SB Chodisetti","year":"2015","unstructured":"Chodisetti, S. B. et al. Triggering through Toll-like receptor 2 limits chronically stimulated T-helper type 1 cells from undergoing exhaustion. The Journal of infectious diseases 211, 486\u2013496 (2015).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep23917_CR23","doi-asserted-by":"publisher","first-page":"E2510","DOI":"10.1073\/pnas.1309171110","volume":"110","author":"F Wang","year":"2013","unstructured":"Wang, F. et al. Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. Proceedings of the National Academy of Sciences 110, E2510\u2013E2517 (2013).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"BFsrep23917_CR24","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/j.1365-2893.2006.00723.x","volume":"13","author":"N Aslan","year":"2006","unstructured":"Aslan, N. et al. Cytotoxic CD4 T cells in viral hepatitis. Journal of viral hepatitis 13, 505\u2013514 (2006).","journal-title":"Journal of viral hepatitis"},{"key":"BFsrep23917_CR25","doi-asserted-by":"publisher","first-page":"5668","DOI":"10.4049\/jimmunol.177.8.5668","volume":"177","author":"A Hombach","year":"2006","unstructured":"Hombach, A., Kohler, H., Rappl, G. & Abken, H. Human CD4+ T cells lyse target cells via granzyme\/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. Journal of immunology 177, 5668\u20135675 (2006).","journal-title":"Journal of immunology"},{"key":"BFsrep23917_CR26","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1002\/(SICI)1521-4141(199906)29:06<1753::AID-IMMU1753>3.0.CO;2-B","volume":"29","author":"JN Agrewala","year":"1999","unstructured":"Agrewala, J. N. & Wilkinson, R. J. Influence of HLA-DR on the phenotype of CD4^+ T lymphocytes specific for an epitope of the 16-kDa -crystallin antigen of Mycobacterium tuberculosis. European journal of immunology 29, 1753\u20131761 (1999).","journal-title":"European journal of immunology"},{"key":"BFsrep23917_CR27","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1182\/blood.V88.9.3513.bloodjournal8893513","volume":"88","author":"D Hamann","year":"1996","unstructured":"Hamann, D., Baars, P. A., Hooibrink, B. & van Lier, R. W. Heterogeneity of the human CD4+ T-cell population: two distinct CD4+ T-cell subsets characterized by coexpression of CD45RA and CD45RO isoforms. Blood 88, 3513\u20133521 (1996).","journal-title":"Blood"},{"key":"BFsrep23917_CR28","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0008-8749(91)90144-Z","volume":"138","author":"JM LaSalle","year":"1991","unstructured":"LaSalle, J. M. & Hafler, D. A. The coexpression of CD45RA and CD45RO isoforms on T cells during the S\/G2\/M stages of cell cycle. Cellular immunology 138, 197\u2013206 (1991).","journal-title":"Cellular immunology"},{"key":"BFsrep23917_CR29","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1164\/rccm.200206-626OC","volume":"167","author":"D Yee","year":"2003","unstructured":"Yee, D. et al. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. American journal of respiratory and critical care medicine 167, 1472\u20131477 (2003).","journal-title":"American journal of respiratory and critical care medicine"},{"key":"BFsrep23917_CR30","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1183\/09031936.96.09102026","volume":"9","author":"T Schaberg","year":"1996","unstructured":"Schaberg, T., Rebhan, K. & Lode, H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. European Respiratory Journal 9, 2026\u20132030 (1996).","journal-title":"European Respiratory Journal"},{"key":"BFsrep23917_CR31","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1016\/j.rmed.2006.01.014","volume":"100","author":"BE Gulbay","year":"2006","unstructured":"Gulbay, B. E. et al. Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis. Respiratory medicine 100, 1834\u20131842 (2006).","journal-title":"Respiratory medicine"},{"key":"BFsrep23917_CR32","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nm.2285","volume":"17","author":"C Aagaard","year":"2011","unstructured":"Aagaard, C. et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nature medicine 17, 189\u2013194 (2011).","journal-title":"Nature medicine"},{"key":"BFsrep23917_CR33","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ijid.2014.12.024","volume":"32","author":"L D\u2019Ambrosio","year":"2015","unstructured":"D\u2019Ambrosio, L. et al. Supporting clinical management of the difficult-to-treat TB cases: the ERS-WHO TB Consilium. International Journal of Infectious Diseases 32, 156\u2013160 (2015).","journal-title":"International Journal of Infectious Diseases"},{"key":"BFsrep23917_CR34","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1136\/thoraxjnl-2012-201663","volume":"67","author":"ZF Udwadia","year":"2012","unstructured":"Udwadia, Z. F. MDR, XDR, TDR tuberculosis: ominous progression. Thorax 67, 286\u2013288 (2012).","journal-title":"Thorax"},{"key":"BFsrep23917_CR35","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","volume":"27","author":"AM Cooper","year":"2009","unstructured":"Cooper, A. M. Cell-mediated immune responses in tuberculosis. Annual review of immunology 27, 393\u2013422 (2009).","journal-title":"Annual review of immunology"},{"key":"BFsrep23917_CR36","doi-asserted-by":"publisher","first-page":"e31908","DOI":"10.1371\/journal.pone.0031908","volume":"7","author":"S Zhao","year":"2012","unstructured":"Zhao, S. et al. Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice. Plos one 7, e31908 (2012).","journal-title":"Plos one"},{"key":"BFsrep23917_CR37","doi-asserted-by":"publisher","first-page":"6092","DOI":"10.1016\/j.vaccine.2008.09.011","volume":"26","author":"SC Derrick","year":"2008","unstructured":"Derrick, S. C. et al. The safety of post-exposure vaccination of mice infected with Mycobacterium tuberculosis. Vaccine 26, 6092\u20136098 (2008).","journal-title":"Vaccine"},{"key":"BFsrep23917_CR38","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1365-2249.2011.04381.x","volume":"164","author":"C Ni Cheallaigh","year":"2011","unstructured":"Ni Cheallaigh, C., Keane, J., Lavelle, E. C., Hope, J. C. & Harris, J. Autophagy in the immune response to tuberculosis: clinical perspectives. Clinical and experimental immunology 164, 291\u2013300 (2011).","journal-title":"Clinical and experimental immunology"},{"key":"BFsrep23917_CR39","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1086\/318817","volume":"183","author":"CS Hirsch","year":"2001","unstructured":"Hirsch, C. S. et al. Augmentation of apoptosis and interferon-gamma production at sites of active Mycobacterium tuberculosis infection in human tuberculosis. The Journal of infectious diseases 183, 779\u2013788 (2001).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep23917_CR40","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.micinf.2009.04.004","volume":"11","author":"F Sallusto","year":"2009","unstructured":"Sallusto, F. & Lanzavecchia, A. Human Th17 cells in infection and autoimmunity. Microbes and infection\/Institut Pasteur 11, 620\u2013624 (2009).","journal-title":"Microbes and infection\/Institut Pasteur"},{"key":"BFsrep23917_CR41","first-page":"110","volume":"184","author":"G Shi","year":"2010","unstructured":"Shi, G. et al. Pathogenic or non-pathogenic subpopulations of Th17 cells are generated by stimulation of na\u00efve CD4 cells via antigen\/APC or anti-CD3\/CD28 antibodies. The Journal of Immunology 184(135), 110 (2010).","journal-title":"The Journal of Immunology"},{"key":"BFsrep23917_CR42","doi-asserted-by":"publisher","first-page":"e60","DOI":"10.1038\/emi.2013.58","volume":"2","author":"W Jin","year":"2013","unstructured":"Jin, W. & Dong, C. IL-17 cytokines in immunity and inflammation. Emerging Microbes & Infections 2, e60 (2013).","journal-title":"Emerging Microbes & Infections"},{"key":"BFsrep23917_CR43","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.tube.2012.12.002","volume":"93","author":"ND Marin","year":"2013","unstructured":"Marin, N. D., Paris, S. C., Rojas, M. & Garcia, L. F. Functional profile of CD4+ and CD8+ T cells in latently infected individuals and patients with active TB. Tuberculosis 93, 155\u2013166 (2013).","journal-title":"Tuberculosis"},{"key":"BFsrep23917_CR44","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1002\/eji.201243090","volume":"43","author":"M Perreau","year":"2013","unstructured":"Perreau, M. et al. Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4+ T cells in active disease. European journal of immunology 43, 939\u2013948 (2013).","journal-title":"European journal of immunology"},{"key":"BFsrep23917_CR45","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1074\/jbc.275.4.2520","volume":"275","author":"B Lei","year":"2000","unstructured":"Lei, B., Wei, C.-J. & Tu, S.-C. Action mechanism of antitubercular isoniazid Activation by Mycobacterium tuberculosis KatG, isolation, and characterization of InhA inhibitor. Journal of Biological Chemistry 275, 2520\u20132526 (2000).","journal-title":"Journal of Biological Chemistry"},{"key":"BFsrep23917_CR46","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1128\/AAC.2.1.29","volume":"2","author":"K Takayama","year":"1972","unstructured":"Takayama, K., Wang, L. & David, H. L. Effect of isoniazid on the in vivo mycolic acid synthesis, cell growth, and viability of Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy 2, 29\u201335 (1972).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"BFsrep23917_CR47","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/S0092-8674(01)00286-0","volume":"104","author":"EA Campbell","year":"2001","unstructured":"Campbell, E. A. et al. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104, 901\u2013912 (2001).","journal-title":"Cell"},{"key":"BFsrep23917_CR48","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1038\/emi.2014.17","volume":"3","author":"A Koch","year":"2014","unstructured":"Koch, A., Mizrahi, V. & Warner, D. F. The impact of drug resistance on Mycobacterium tuberculosis physiology: what can we learn from rifampicin? Emerging Microbes & Infections 3, e17 (2014).","journal-title":"Emerging Microbes & Infections"},{"key":"BFsrep23917_CR49","doi-asserted-by":"publisher","first-page":"15440","DOI":"10.1073\/pnas.0406740101","volume":"101","author":"DC Jackson","year":"2004","unstructured":"Jackson, D. C. et al. A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proceedings of the National Academy of Sciences of the United States of America 101, 15440\u201315445 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep23917_CR50","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1086\/421116","volume":"190","author":"N Sharma","year":"2004","unstructured":"Sharma, N. & Agrewala, J. N. Potent role of vaccines prepared from macrophages infected with live bacteria in protection against Mycobacterium tuberculosis and Salmonella typhimurium infections. The Journal of infectious diseases 190, 107\u2013114 (2004).","journal-title":"The Journal of infectious diseases"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep23917.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23917","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23917.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:46:49Z","timestamp":1672890409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep23917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,7]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,29]]}},"alternative-id":["BFsrep23917"],"URL":"https:\/\/doi.org\/10.1038\/srep23917","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,7]]},"assertion":[{"value":"25 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23917"}}