{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T02:26:08Z","timestamp":1775183168168,"version":"3.50.1"},"reference-count":189,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-FAR\/30266\/2017"],"award-info":[{"award-number":["PTDC\/MED-FAR\/30266\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/131896\/2017"],"award-info":[{"award-number":["SFRH\/BD\/131896\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04138\/2020 and UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020 and UIDP\/04138\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002924","name":"FEDER","doi-asserted-by":"publisher","award":["PTDC\/MED-FAR\/30266\/2017"],"award-info":[{"award-number":["PTDC\/MED-FAR\/30266\/2017"]}],"id":[{"id":"10.13039\/501100002924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite being discovered and isolated more than one hundred years ago, tuberculosis (TB) remains a global public health concern arch. Our inability to eradicate this bacillus is strongly related with the growing resistance, low compliance to current drugs, and the capacity of the bacteria to coexist in a state of asymptomatic latency. This last state can be sustained for years or even decades, waiting for a breach in the immune system to become active again. Furthermore, most current therapies are not efficacious against this state, failing to completely clear the infection. Over the years, a series of experimental methods have been developed to mimic the latent state, currently used in drug discovery, both in vitro and in vivo. Most of these methods focus in one specific latency inducing factor, with only a few taking into consideration the complexity of the granuloma and the genomic and proteomic consequences of each physiological factor. A series of targets specifically involved in latency have been studied over the years with promising scaffolds being discovered and explored. Taking in account that solving the latency problem is one of the keys to eradicate the disease, herein we compile current therapies and diagnosis techniques, methods to mimic latency and new targets and compounds in the pipeline of drug discovery.<\/jats:p>","DOI":"10.3390\/ijms21228854","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T08:18:23Z","timestamp":1606119503000},"page":"8854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Addressing Latent Tuberculosis: New Advances in Mimicking the Disease, Discovering Key Targets, and Designing Hit Compounds"],"prefix":"10.3390","volume":"21","author":[{"given":"Andr\u00e9","family":"Campani\u00e7o","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Shrika G.","family":"Harjivan","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-0930","authenticated-orcid":false,"given":"Digby F.","family":"Warner","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa"},{"name":"Department of Pathology, SAMRC\/NHLS\/UCT Molecular Mycobacteriology Research Unit, University of Cape Town, Rondebosch 7701, South Africa"},{"name":"Welcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Rondebosch 7701, South Africa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0727-9852","authenticated-orcid":false,"given":"Rui","family":"Moreira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5350-147X","authenticated-orcid":false,"given":"Francisca","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1016\/j.ijid.2009.12.003","article-title":"Robert Koch and the \u2018golden age\u2019 of bacteriology","volume":"14","author":"Blevins","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ejmech.2018.03.020","article-title":"Drug discovery in tuberculosis. New drug targets and antimycobacterial agents","volume":"150","author":"Campanico","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_3","unstructured":"World Health Organization (2019). Global Tuberculosis Report 2019, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1039\/C9MD00057G","article-title":"Drug-resistance in Mycobacterium tuberculosis: Where we stand","volume":"10","author":"Mabhula","year":"2019","journal-title":"MedChemComm"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1473-3099(17)30248-7","article-title":"Latent tuberculosis infection: The final frontier of tuberculosis elimination in the USA","volume":"17","author":"LoBue","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.4049\/jimmunol.175.2.1107","article-title":"Long-term control of Mycobacterium tuberculosis infection is mediated by dynamic immune responses","volume":"175","author":"Lazarevic","year":"2005","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1128\/IAI.01515-07","article-title":"Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates","volume":"76","author":"Via","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1128\/iai.64.6.2062-2069.1996","article-title":"An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence","volume":"64","author":"Wayne","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1128\/JB.00926-09","article-title":"The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy","volume":"192","author":"Leistikow","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1046\/j.1365-2958.2003.03474.x","article-title":"Rv3133c\/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis","volume":"48","author":"Park","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/resp.13346","article-title":"Latent tuberculosis infection: Opportunities and challenges","volume":"23","author":"Chee","year":"2018","journal-title":"Respirology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/oxfordjournals.aje.a121593","article-title":"The prognosis of a positive tuberculin reaction in childhood and adolescence","volume":"99","author":"Comstock","year":"1974","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1056\/NEJMcp1005750","article-title":"Clinical practice. Latent tuberculosis infection in the United States","volume":"364","author":"Horsburgh","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_14","unstructured":"CDC (2013). Treatment of Tuberculosis Disease. Core Curriculum on Tuberculosis: What the Clinician Should Know, CDC. [6th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e183","DOI":"10.1016\/S1473-3099(18)30110-5","article-title":"Tuberculosis: Progress and advances in development of new drugs, treatment regimens, and host-directed therapies","volume":"18","author":"Tiberi","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Connolly, L.E., Edelstein, P.H., and Ramakrishnan, L. (2007). Why is long-term therapy required to cure tuberculosis?. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040120"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Houben, R.M., and Dodd, P.J. (2016). The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002152"},{"key":"ref_18","unstructured":"World Health Organization (2018). EndTB Strategy, World Health Organization."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ccm.2019.07.008","article-title":"Treatment of Latent Tuberculosis Infection\u2014An Update","volume":"40","author":"Huaman","year":"2019","journal-title":"Clin. Chest Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/S0140-6736(14)60162-8","article-title":"Isoniazid plus antiretroviral therapy to prevent tuberculosis: A randomised double-blind, placebo-controlled trial","volume":"384","author":"Rangaka","year":"2014","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.7326\/M17-0609","article-title":"Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis","volume":"167","author":"Zenner","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_22","first-page":"847","article-title":"How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults?","volume":"3","author":"Comstock","year":"1999","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4046\/trd.2017.0052","article-title":"Treatment of Latent Tuberculosis Infection and Its Clinical Efficacy","volume":"81","author":"Kim","year":"2018","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1164\/rccm.200212-1483OC","article-title":"Risk factors for tuberculosis infection in sub-Saharan Africa: A contact study in The Gambia","volume":"168","author":"Lienhardt","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","first-page":"851","article-title":"Prevalence and risk factors associated with tuberculin skin test positivity among household contacts of smear-positive pulnionary tuberculosis cases in Umerkot, Pakistan","volume":"6","author":"Rathi","year":"2002","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1128\/AAC.02154-12","article-title":"Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions","volume":"57","author":"Piccaro","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nrd4001","article-title":"Advances in the development of new tuberculosis drugs and treatment regimens","volume":"12","author":"Zumla","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1128\/AAC.00086-07","article-title":"Isoniazid induces its own resistance in nonreplicating Mycobacterium tuberculosis","volume":"51","author":"Siddiqi","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/ijmy.ijmy_85_17","article-title":"Fighting tuberculosis by drugs targeting nonreplicating Mycobacterium tuberculosis bacilli","volume":"6","author":"Iacobino","year":"2017","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1056\/NEJMoa1714283","article-title":"Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults","volume":"379","author":"Menzies","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"689","DOI":"10.7326\/0003-4819-149-10-200811180-00003","article-title":"Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: A randomized trial","volume":"149","author":"Menzies","year":"2008","journal-title":"Ann. Intern. Med."},{"key":"ref_32","unstructured":"(2001). Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection--New York and Georgia, 2000. MMWR Morb. Mortal. Wkly. Rep., 50, 289\u2013291."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1164\/rccm.200206-626OC","article-title":"Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis","volume":"167","author":"Yee","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1473-3099(19)30059-3","article-title":"Latent tuberculosis infection: Diagnostic tests and when to treat","volume":"19","author":"Petersen","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.ccm.2019.07.007","article-title":"Diagnostic Tests for Latent Tuberculosis Infection","volume":"40","author":"Haas","year":"2019","journal-title":"Clin. Chest Med."},{"key":"ref_36","first-page":"1192","article-title":"False-positive tuberculin skin tests: What is the absolute effect of BCG and non-tuberculous mycobacteria?","volume":"10","author":"Farhat","year":"2006","journal-title":"Int. J. Tuberc Lung Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(00)02742-2","article-title":"Specific immune-based diagnosis of tuberculosis","volume":"356","author":"Andersen","year":"2000","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1128\/IAI.70.5.2544-2548.2002","article-title":"Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis","volume":"70","author":"Geluk","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1183\/09031936.00120908","article-title":"LTBI: Latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement","volume":"33","author":"Mack","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/596735","article-title":"Association between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3-expressing cells in HIV-infected persons","volume":"199","author":"Sarrazin","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1183\/13993003.01910-2015","article-title":"Diagnostics for latent TB infection: Incremental, not transformative progress","volume":"47","author":"Pai","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gibson, S.E.R., Harrison, J., and Cox, J.A.G. (2018). Modelling a Silent Epidemic: A Review of the In Vitro Models of Latent Tuberculosis. Pathogens, 7.","DOI":"10.20944\/preprints201810.0701.v2"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1136\/thoraxjnl-2015-207402","article-title":"Hypoxia and tissue destruction in pulmonary TB","volume":"71","author":"Belton","year":"2016","journal-title":"Thorax"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/jb.26.2.167-200.1933","article-title":"The Influence of Adverse Conditions upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli","volume":"26","author":"Loebel","year":"1933","journal-title":"J. Bacteriol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1128\/iai.9.5.843-850.1974","article-title":"Studies on the effect of starvation on mycobacteria","volume":"9","author":"Nyka","year":"1974","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fimmu.2013.00098","article-title":"Modeling the Mycobacterium tuberculosis Granuloma - the Critical Battlefield in Host Immunity and Disease","volume":"4","author":"Guirado","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_47","first-page":"807","article-title":"Dynamics of submerged growth of Mycobacterium tuberculosis under aerobic and microaerophilic conditions","volume":"114","author":"Wayne","year":"1976","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.micro.55.1.139","article-title":"Nonreplicating persistence of Mycobacterium tuberculosis","volume":"55","author":"Wayne","year":"2001","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.tube.2004.02.003","article-title":"Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy","volume":"84","author":"Voskuil","year":"2004","journal-title":"Tuberculosis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1128\/JB.183.8.2672-2676.2001","article-title":"Proteins of Mycobacterium bovis BCG induced in the Wayne dormancy model","volume":"183","author":"Boon","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_51","first-page":"247","article-title":"In Vitro Model of Hypoxically Induced Nonreplicating Persistence of Mycobacterium tuberculosis","volume":"54","author":"Wayne","year":"2001","journal-title":"Methods Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1128\/AAC.38.9.2054","article-title":"Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis","volume":"38","author":"Wayne","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1128\/AAC.00196-08","article-title":"Metronidazole lacks antibacterial activity in guinea pigs infected with Mycobacterium tuberculosis","volume":"52","author":"Hoff","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1086\/589515","article-title":"Metronidazole lacks activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency","volume":"198","author":"Klinkenberg","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14188","DOI":"10.1073\/pnas.1121497109","article-title":"Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques","volume":"109","author":"Lin","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.tube.2012.07.003","article-title":"Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis","volume":"92","author":"Franzblau","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/jac\/dkm207","article-title":"Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis","volume":"60","author":"Taneja","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Aher, R.B., and Sarkar, D. (2020). Pharmacophore modeling of pretomanid (PA-824) derivatives for antitubercular potency against replicating and non-replicating Mycobacterium tuberculosis. J. Biomol. Struct. Dyn., 1\u201312.","DOI":"10.1080\/07391102.2020.1719205"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bonnett, S.A., Dennison, D., Files, M., Bajpai, A., and Parish, T. (2018). A class of hydrazones are active against non-replicating Mycobacterium tuberculosis. PLoS ONE, 13.","DOI":"10.1101\/323220"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/978-1-4939-2450-9_17","article-title":"Microplate Alamar Blue Assay (MABA) and Low Oxygen Recovery Assay (LORA) for Mycobacterium tuberculosis","volume":"1285","author":"Cho","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1128\/IAI.67.9.4586-4593.1999","article-title":"Assessment of immunity to mycobacterial infection with luciferase reporter constructs","volume":"67","author":"Snewin","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1128\/AAC.00055-06","article-title":"Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis","volume":"51","author":"Cho","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.tube.2018.02.008","article-title":"Novel red fluorescence protein based microplate assay for drug screening against dormant Mycobacterium tuberculosis by using paraffin","volume":"110","author":"Yeware","year":"2018","journal-title":"Tuberculosis"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Carroll, P., Schreuder, L.J., Muwanguzi-Karugaba, J., Wiles, S., Robertson, B.D., Ripoll, J., Ward, T.H., Bancroft, G.J., Schaible, U.E., and Parish, T. (2010). Sensitive detection of gene expression in mycobacteria under replicating and non-replicating conditions using optimized far-red reporters. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009823"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/nmeth819","article-title":"A guide to choosing fluorescent proteins","volume":"2","author":"Shaner","year":"2005","journal-title":"Nat. Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/jb.26.2.139-166.1933","article-title":"The Influence of Foodstuffs upon the Respiratory Metabolism and Growth of Human Tubercle Bacilli","volume":"26","author":"Loebel","year":"1933","journal-title":"J. Bacteriol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1046\/j.1365-2958.2002.02779.x","article-title":"Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling","volume":"43","author":"Betts","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Murphy, D.J., and Brown, J.R. (2007). Identification of gene targets against dormant phase Mycobacterium tuberculosis infections. BMC Infect. Dis., 7.","DOI":"10.1186\/1471-2334-7-84"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.tube.2003.12.010","article-title":"Stationary phase gene expression of Mycobacterium tuberculosis following a progressive nutrient depletion: A model for persistent organisms?","volume":"84","author":"Hampshire","year":"2004","journal-title":"Tuberculosis"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.niox.2016.06.009","article-title":"The emerging role of gasotransmitters in the pathogenesis of tuberculosis","volume":"59","author":"Chinta","year":"2016","journal-title":"Nitric Oxide"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1084\/jem.20030205","article-title":"Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program","volume":"198","author":"Voskuil","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1054\/tuld.1998.0015","article-title":"Nitrate reduction as a marker for hypoxic shiftdown of Mycobacterium tuberculosis","volume":"79","author":"Wayne","year":"1998","journal-title":"Tuber. Lung Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tube.2016.04.006","article-title":"Mycobacterium tuberculosis strain 18b, a useful non-virulent streptomycin dependent mutant to study latent tuberculosis as well as for in vivo and in vitro testing of anti-tuberculosis drugs","volume":"99","year":"2016","journal-title":"Tuberculosis"},{"key":"ref_74","first-page":"4","article-title":"Experimental studies on the mechanism of infection and immunity in tuberculosis from the analytical standpoint of streptomycin-dependent tubercle bacilli. Isolation and biological characteristics of a streptomycin-dependent mutant, and effect of streptomycin administration on its pathogenicity in guinea-pigs","volume":"30","author":"Hashimoto","year":"1955","journal-title":"Kekkaku"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1128\/AAC.00821-10","article-title":"Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis","volume":"54","author":"Sala","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5782","DOI":"10.1128\/AAC.01125-12","article-title":"Streptomycin-starved Mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis","volume":"56","author":"Zhang","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1021\/acs.jmedchem.5b00608","article-title":"Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis","volume":"59","author":"Karabanovich","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1128\/AAC.02410-14","article-title":"In vitro and in vivo activities of three oxazolidinones against nonreplicating Mycobacterium tuberculosis","volume":"58","author":"Zhang","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Deb, C., Lee, C.M., Dubey, V.S., Daniel, J., Abomoelak, B., Sirakova, T.D., Pawar, S., Rogers, L., and Kolattukudy, P.E. (2009). A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006077"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-4939-2450-9_18","article-title":"A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis","volume":"1285","author":"Gold","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nchembio.109","article-title":"Identification of a copper-binding metallothionein in pathogenic mycobacteria","volume":"4","author":"Gold","year":"2008","journal-title":"Nature Chem. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1046\/j.1365-2958.2001.02684.x","article-title":"The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages","volume":"42","author":"Gold","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1128\/IAI.68.5.2888-2898.2000","article-title":"Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis","volume":"68","author":"Hondalus","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/j.1365-2958.2004.04078.x","article-title":"Role of KatG catalase-peroxidase in mycobacterial pathogenesis: Countering the phagocyte oxidative burst","volume":"52","author":"Ng","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1128\/IAI.70.7.3371-3381.2002","article-title":"ideR, An essential gene in mycobacterium tuberculosis: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response","volume":"70","author":"Rodriguez","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nm765","article-title":"A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis","volume":"8","author":"Sambandamurthy","year":"2002","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e00876-13","DOI":"10.1128\/mBio.00876-13","article-title":"The Copper-Responsive RicR Regulon Contributes to Mycobacterium tuberculosis Virulence","volume":"5","author":"Shi","year":"2014","journal-title":"mBio"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.chom.2008.03.007","article-title":"Mycobacterium tuberculosis Senses Host-Derived Carbon Monoxide during Macrophage Infection","volume":"3","author":"Shiloh","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14321","DOI":"10.1073\/pnas.2436197100","article-title":"Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients","volume":"100","author":"Timm","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1365-2958.2006.05102.x","article-title":"The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis","volume":"60","author":"Walters","year":"2006","journal-title":"Mol. Microb."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1128\/MMBR.00010-14","article-title":"Latent tuberculosis infection: Myths, models, and molecular mechanisms","volume":"78","author":"Dutta","year":"2014","journal-title":"Microb. Mol. Biol. Rev. MMBR"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1146\/annurev.micro.57.030502.091033","article-title":"The secret lives of the pathogenic mycobacteria","volume":"57","author":"Cosma","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.0959-9673.2004.00379.x","article-title":"Pathological and immunological profiles of rat tuberculosis","volume":"85","author":"Sugawara","year":"2004","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.tube.2005.08.008","article-title":"Animal models of tuberculosis","volume":"85","author":"Gupta","year":"2005","journal-title":"Tuberculosis"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cbpc.2006.07.012","article-title":"Mycobacterium marinum produces long-term chronic infections in medaka: A new animal model for studying human tuberculosis","volume":"145","author":"Broussard","year":"2007","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_96","first-page":"e58299","article-title":"Modeling Tuberculosis in Mycobacterium marinum Infected Adult Zebrafish","volume":"140","author":"Luukinen","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6108","DOI":"10.1128\/IAI.00887-06","article-title":"Mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity","volume":"74","author":"Swaim","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1084\/jem.123.3.469","article-title":"Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli","volume":"123","author":"McCune","year":"1966","journal-title":"J. Exp. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1084\/jem.104.5.763","article-title":"The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug","volume":"104","author":"McCune","year":"1956","journal-title":"J. Exp. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1574-6968.2006.00224.x","article-title":"The potential of azole antifungals against latent\/persistent tuberculosis","volume":"258","author":"Ahmad","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1128\/IAI.00918-06","article-title":"In Vivo Adaptation of the Wayne Model of Latent Tuberculosis","volume":"75","author":"Woolhiser","year":"2007","journal-title":"Infect Immun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1128\/IAI.71.4.1672-1679.2003","article-title":"A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis","volume":"71","author":"Horwitz","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1128\/IAI.72.2.1065-1071.2004","article-title":"Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with Mycobacterium bovis BCG","volume":"72","author":"Nuermberger","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/j.ajpath.2014.03.008","article-title":"Characterization of a Novel Necrotic Granuloma Model of Latent Tuberculosis Infection and Reactivation in Mice","volume":"184","author":"Dutta","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1084\/jem.20040646","article-title":"Dormancy Phenotype Displayed by Extracellular Mycobacterium tuberculosis within Artificial Granulomas in Mice","volume":"200","author":"Karakousis","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.jmii.2014.03.005","article-title":"Recombinant tuberculosis vaccine AEC\/BC02 induces antigen-specific cellular responses in mice and protects guinea pigs in a model of latent infection","volume":"48","author":"Lu","year":"2015","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0041-3879(88)90051-7","article-title":"The protective and allergenic potency of four BCG substrains in use in China determined in two animal models","volume":"69","author":"Balasubramanian","year":"1988","journal-title":"Tubercle"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.micinf.2008.08.010","article-title":"Guinea pig model of Mycobacterium tuberculosis latent\/dormant infection","volume":"10","author":"Kashino","year":"2008","journal-title":"Microbes Infect."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.tube.2007.10.006","article-title":"The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome","volume":"88","author":"Manabe","year":"2008","journal-title":"Tuberculosis"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/tbed.12474","article-title":"Mycobacterial Infections in Rabbits: From the Wild to the Laboratory","volume":"64","author":"Arrazuria","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.ajpath.2012.07.019","article-title":"Spontaneous latency in a rabbit model of pulmonary tuberculosis","volume":"181","author":"Subbian","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e00505","DOI":"10.1128\/IAI.00505-17","article-title":"Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: A Quantitative Comparison","volume":"86","author":"Maiello","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1128\/IAI.71.10.5831-5844.2003","article-title":"Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection","volume":"71","author":"Capuano","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41586-019-1817-8","article-title":"Prevention of tuberculosis in macaques after intravenous BCG immunization","volume":"577","author":"Darrah","year":"2020","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Diedrich, C.R., Mattila, J.T., Klein, E., Janssen, C., Phuah, J., Sturgeon, T.J., Montelaro, R.C., Lin, P.L., and Flynn, J.L. (2010). Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009611"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1172\/JCI46252","article-title":"The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection","volume":"122","author":"Lin","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nm.3412","article-title":"Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing","volume":"20","author":"Lin","year":"2014","journal-title":"Nat. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/art.27271","article-title":"Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model","volume":"62","author":"Lin","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1128\/IAI.00592-09","article-title":"Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model","volume":"77","author":"Lin","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1128\/IAI.02850-14","article-title":"Monkey models of tuberculosis: Lessons learned","volume":"83","author":"Ho","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112907","DOI":"10.18632\/oncotarget.22889","article-title":"Genome-wide transcriptional profiling identifies potential signatures in discriminating active tuberculosis from latent infection","volume":"8","author":"Pan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jmhi.2013.04.002","article-title":"A novel approach to eradicate latent TB: Based on resuscitation promoting factors","volume":"7","author":"Seidi","year":"2013","journal-title":"J. Med Hypotheses Ideas"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"15629","DOI":"10.1073\/pnas.0507850102","article-title":"Changes in energy metabolism of Mycobacterium tuberculosis in mouse lung and under in vitro conditions affecting aerobic respiration","volume":"102","author":"Shi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"7247","DOI":"10.1128\/JB.185.24.7247-7256.2003","article-title":"Role of narK2X and narGHJI in hypoxic upregulation of nitrate reduction by Mycobacterium tuberculosis","volume":"185","author":"Sohaskey","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1128\/JB.01857-07","article-title":"Nitrate enhances the survival of Mycobacterium tuberculosis during inhibition of respiration","volume":"190","author":"Sohaskey","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1128\/JB.05914-11","article-title":"ald of Mycobacterium tuberculosis encodes both the alanine dehydrogenase and the putative glycine dehydrogenase","volume":"194","author":"Giffin","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1128\/JB.181.23.7161-7167.1999","article-title":"Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis","volume":"181","author":"Miczak","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Giffin, M.M., Shi, L., Gennaro, M.L., and Sohaskey, C.D. (2016). Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155522"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.drudis.2017.04.012","article-title":"Targeting isocitrate lyase for the treatment of latent tuberculosis","volume":"22","author":"Bhusal","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.compbiolchem.2013.07.002","article-title":"A systems chemical biology study of malate synthase and isocitrate lyase inhibition in Mycobacterium tuberculosis during active and NRP growth","volume":"47","author":"May","year":"2013","journal-title":"Comput. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jmgm.2013.08.005","article-title":"Identification of novel inhibitors against Mycobacterium tuberculosis L-alanine dehydrogenase (MTB-AlaDH) through structure-based virtual screening","volume":"47","author":"Saxena","year":"2014","journal-title":"J. Mol. Graph. Model."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ejmech.2014.12.046","article-title":"Design and development of novel Mycobacterium tuberculosis L-alanine dehydrogenase inhibitors","volume":"92","author":"Saxena","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1016\/j.bmc.2016.07.051","article-title":"Design and development of new class of Mycobacterium tuberculosis L-alanine dehydrogenase inhibitors","volume":"24","author":"Reshma","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.1016\/j.bmc.2016.09.012","article-title":"Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis","volume":"24","author":"Samala","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1016\/j.bmcl.2011.07.062","article-title":"Synthesis of various 3-nitropropionamides as Mycobacterium tuberculosis isocitrate lyase inhibitor","volume":"21","author":"Sriram","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/35021074","article-title":"Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase","volume":"406","author":"McKinney","year":"2000","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ejmech.2012.07.044","article-title":"Synthesis and in vitro antimycobacterial activity of 2-methoxybenzanilides and their thioxo analogues","volume":"56","author":"Kozic","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.tube.2015.12.003","article-title":"Identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating Mycobacterium tuberculosis","volume":"97","author":"Liu","year":"2016","journal-title":"Tuberculosis"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1600-065X.2010.00994.x","article-title":"For better or for worse: The immune response against Mycobacterium tuberculosis balances pathology and protection","volume":"240","author":"Dorhoi","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1089\/ars.2019.7867","article-title":"Reductive Stress: New Insights in Physiology and Drug Tolerance of Mycobacterium","volume":"32","author":"Mavi","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1039\/b616489g","article-title":"Mycothiol: Synthesis, biosynthesis and biological functions of the major low molecular weight thiol in actinomycetes","volume":"25","author":"Jothivasan","year":"2008","journal-title":"Nat. Prod. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1084\/jem.20030846","article-title":"Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment","volume":"198","author":"Schnappinger","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"6848","DOI":"10.1021\/acs.jmedchem.6b00674","article-title":"Inhibitors of the Cysteine Synthase CysM with Antibacterial Potency against Dormant Mycobacterium tuberculosis","volume":"59","author":"Brunner","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1021\/acschembio.5b00517","article-title":"First-in-Class Inhibitors of Sulfur Metabolism with Bactericidal Activity against Non-Replicating, M. tuberculosis","volume":"11","author":"Palde","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.bbapap.2014.11.010","article-title":"Pyridoxal-phosphate dependent mycobacterial cysteine synthases: Structure, mechanism and potential as drug targets","volume":"1854","author":"Schnell","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"12989","DOI":"10.1073\/pnas.2134250100","article-title":"Genetic requirements for mycobacterial survival during infection","volume":"100","author":"Sassetti","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1016\/j.bmcl.2017.08.039","article-title":"Profiling of in vitro activities of urea-based inhibitors against cysteine synthases from Mycobacterium tuberculosis","volume":"27","author":"Brunner","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2174\/187152607781001772","article-title":"Drug targets in mycobacterial sulfur metabolism","volume":"7","author":"Bhave","year":"2007","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1007\/s00203-002-0469-4","article-title":"Mycothiol biochemistry","volume":"178","author":"Newton","year":"2002","journal-title":"Arch. Microbiol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Hatzios, S.K., and Bertozzi, C.R. (2011). The regulation of sulfur metabolism in Mycobacterium tuberculosis. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002036"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"32606","DOI":"10.1074\/jbc.M204613200","article-title":"5\u2019-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria","volume":"277","author":"Williams","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Carroll, K.S., Gao, H., Chen, H., Stout, C.D., Leary, J.A., and Bertozzi, C.R. (2005). A conserved mechanism for sulfonucleotide reduction. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030250"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/15257770.2014.978012","article-title":"Design, synthesis and evaluation of Fe-S targeted adenosine 5\u2019-phosphosulfate reductase inhibitors","volume":"34","author":"Paritala","year":"2015","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1021\/jm900728u","article-title":"Identification of critical ligand binding determinants in Mycobacterium tuberculosis adenosine-5\u2019-phosphosulfate reductase","volume":"52","author":"Hong","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1021\/jm800571m","article-title":"Structure-based virtual screening and biological evaluation of Mycobacterium tuberculosis adenosine 5\u2019-phosphosulfate reductase inhibitors","volume":"51","author":"Cosconati","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/bs.ampbs.2017.05.001","article-title":"Chapter Five\u2014Haem-Based Sensors of O2: Lessons and Perspectives","volume":"71","author":"Sousa","year":"2017","journal-title":"Adv. Microb. Physiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4155\/fmc-2019-0263","article-title":"Inhibiting DosRST as a new approach to tuberculosis therapy","volume":"12","author":"Zheng","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1054\/tuld.2000.0240","article-title":"Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis","volume":"80","author":"Dasgupta","year":"2000","journal-title":"Tuberc. Lung Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1110\/ps.072897707","article-title":"DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis","volume":"16","author":"Sousa","year":"2007","journal-title":"Protein Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"23082","DOI":"10.1074\/jbc.M401230200","article-title":"Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis","volume":"279","author":"Roberts","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00775-020-01803-1","article-title":"Potential therapeutic approaches for a sleeping pathogen: Tuberculosis a case for bioinorganic chemistry","volume":"25","author":"Sousa","year":"2020","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1021\/jm900358q","article-title":"Structure-based design of DevR inhibitor active against nonreplicating Mycobacterium tuberculosis","volume":"52","author":"Gupta","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nchembio.2259","article-title":"Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence","volume":"13","author":"Zheng","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/acschembio.8b00849","article-title":"Inhibiting Mycobacterium tuberculosis DosRST Signaling by Targeting Response Regulator DNA Binding and Sensor Kinase Heme","volume":"15","author":"Zheng","year":"2020","journal-title":"ACS Chem. Biol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1021\/cb2004884","article-title":"A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis","volume":"7","author":"Mak","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1021\/bi00851a045","article-title":"L-lysine-.alpha.-ketoglutarate aminotransferase. I. Identification of a product, DELTA.1-piperideine-6-carboxylic acid","volume":"7","author":"Soda","year":"1968","journal-title":"Biochemistry"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1021\/bi00851a046","article-title":"L-lysine-.alpha.-ketoglutarate aminotransferase. II. Purification, crystallization, and properties","volume":"7","author":"Soda","year":"1968","journal-title":"Biochemistry"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"19695","DOI":"10.1038\/srep19695","article-title":"Mycobacterium Lysine \u03b5-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level","volume":"6","author":"Duan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.tube.2015.04.010","article-title":"Discovery of novel lysine \u025b-aminotransferase inhibitors: An intriguing potential target for latent tuberculosis","volume":"95","author":"Devi","year":"2015","journal-title":"Tuberculosis"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/cbdd.12655","article-title":"Design and Development of Mycobacterium tuberculosis Lysine \u025b-Aminotransferase Inhibitors for Latent Tuberculosis Infection","volume":"87","author":"Parthiban","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1016\/j.bmc.2017.03.053","article-title":"Mycobacterium tuberculosis lysine-\u025b-aminotransferase a potential target in dormancy: Benzothiazole based inhibitors","volume":"25","author":"Reshma","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"112757","DOI":"10.1016\/j.ejmech.2020.112757","article-title":"FabI (enoyl acyl carrier protein reductase) - A potential broad spectrum therapeutic target and its inhibitors","volume":"208","author":"Rana","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1093\/infdis\/jiaa042","article-title":"Isoniazid and Rifampin-Resistance Mutations Associated with Resistance to Second-Line Drugs and With Sputum Culture Conversion","volume":"221","author":"Click","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cmi.2020.07.004","article-title":"Identifying isoniazid resistance markers to guide inclusion of high-dose isoniazid in tuberculosis treatment regimens","volume":"26","author":"Whitfield","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"112402","DOI":"10.1016\/j.ejmech.2020.112402","article-title":"Design and synthesis of thiourea-based derivatives as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors","volume":"199","author":"Krishna","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2174\/1568026619666190219105722","article-title":"Mycobacterial tuberculosis Enzyme Targets and their Inhibitors","volume":"19","author":"Saxena","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"127192","DOI":"10.1016\/j.bmcl.2020.127192","article-title":"Identification of 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamides as a novel class of potent DprE1 inhibitors","volume":"30","author":"Whitehurst","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e02020-19","DOI":"10.1128\/AAC.02020-19","article-title":"OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor","volume":"64","author":"Hariguchi","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"112773","DOI":"10.1016\/j.ejmech.2020.112773","article-title":"Design, synthesis and evaluation of covalent inhibitors of DprE1 as antitubercular agents","volume":"208","author":"Liu","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/emmm.201201772","article-title":"Tuberculosis drug discovery in the post-post-genomic era","volume":"6","author":"Lechartier","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1039\/C8MD00055G","article-title":"Triazole-diindolylmethane conjugates as new antitubercular agents: Synthesis, bioevaluation, and molecular docking","volume":"9","author":"Danne","year":"2018","journal-title":"MedChemComm"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"7426","DOI":"10.1073\/pnas.0812191106","article-title":"Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis","volume":"106","author":"Belin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jinorgbio.2018.01.010","article-title":"Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system","volume":"180","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"9311","DOI":"10.1002\/anie.201202544","article-title":"Application of fragment screening and merging to the discovery of inhibitors of the Mycobacterium tuberculosis cytochrome P450 CYPA121","volume":"51","author":"Hudson","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1111\/cbdd.13040","article-title":"Synthesis, biological evaluation, and molecular docking studies of novel 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles derivatives targeting Mycobacterium tuberculosis","volume":"90","author":"Rode","year":"2017","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1515\/hsz-2012-0106","article-title":"Functional characterization of the Mycobacterium tuberculosis zinc metallopeptidase Zmp1 and identification of potential substrates","volume":"393","author":"Petrera","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"32475","DOI":"10.1074\/jbc.M111.271809","article-title":"Crystal structure of Mycobacterium tuberculosis zinc-dependent metalloprotease-1 (Zmp1), a metalloprotease involved in pathogenicity","volume":"286","author":"Ferraris","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3389\/fmicb.2016.01347","article-title":"Mycobacterium tuberculosis Zinc Metalloprotease-1 Assists Mycobacterial Dissemination in Zebrafish","volume":"7","author":"Vemula","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ejmech.2016.09.059","article-title":"Quinolidene-rhodanine conjugates: Facile synthesis and biological evaluation","volume":"125","author":"Subhedar","year":"2017","journal-title":"Eur. J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:36:03Z","timestamp":1760178963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":189,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21228854"],"URL":"https:\/\/doi.org\/10.3390\/ijms21228854","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}