{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:47:34Z","timestamp":1792205254739,"version":"4.4.0"},"reference-count":210,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen\u2019s favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.<\/jats:p>","DOI":"10.3390\/molecules27206985","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:31:01Z","timestamp":1666053061000},"page":"6985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-9847","authenticated-orcid":false,"given":"Ali A.","family":"Rabaan","sequence":"first","affiliation":[{"name":"Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas Al","family":"Mutair","sequence":"additional","affiliation":[{"name":"Research Center, Almoosa Specialist Hospital, Al-Ahsa 36342, Saudi Arabia"},{"name":"College of Nursing, Princess Norah bint Abdulrahman University, Riyadh 11564, Saudi Arabia"},{"name":"School of Nursing, Wollongong University, Wollongong, NSW 2522, Australia"},{"name":"Nursing Department, Prince Sultan Military College of Health Sciences, Dhahran 33048, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawra","family":"Albayat","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, King Saud Medical City, Riyadh 7790, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-4117","authenticated-orcid":false,"given":"Jawaher","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Sulaiman","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Medical Specialties Department, King Fahad Medical City, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-2809","authenticated-orcid":false,"given":"Mohammed","family":"Aljeldah","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin 39831, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3522-0607","authenticated-orcid":false,"given":"Basim R. Al","family":"Shammari","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin 39831, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal H.","family":"Alfaraj","sequence":"additional","affiliation":[{"name":"Pediatric Department, Abqaiq General Hospital, First Eastern Health Cluster, Abqaiq 33261, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-0642","authenticated-orcid":false,"given":"Mona A.","family":"Al Fares","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Alwarthan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-5074","authenticated-orcid":false,"given":"Abdulwahab Z.","family":"Binjomah","sequence":"additional","affiliation":[{"name":"Microbiology Department, Riyadh Regional Laboratory and Blood Bank, Riyadh 12746, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 21423, Saudi Arabia"},{"name":"Infectious Disease Department, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem M.","family":"Alhani","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Disease, Maternity and Children Hospital, Dammam 31176, Saudi Arabia"},{"name":"Department of Infection Control, Maternity and Children Hospital, Dammam 31176, Saudi Arabia"},{"name":"Preventive Medicine and Infection Prevention and Control Department, Directorate of Ministry of Health, Dammam 32245, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-1472","authenticated-orcid":false,"given":"Mohammed S.","family":"Almogbel","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 4030, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmonem A.","family":"Abuzaid","sequence":"additional","affiliation":[{"name":"Medical Microbiology Department, Security Forces Hospital Programme, Dammam 32314, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaya","family":"Alqurainees","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Prince Mohammed Bin Abdulaziz Hospital, Ministry of National Guard Health Affairs, Medina 41511, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimah","family":"Al Ibrahim","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Department of Internal Medicine, Dammam Medical Complex, Dammam 32245, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali H.","family":"Alhaddad","sequence":"additional","affiliation":[{"name":"Assistant Agency for Hospital Affairs, Ministry of Health, Riyadh 12382, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2523-835X","authenticated-orcid":false,"given":"Mubarak","family":"Alfaresi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Sheikh Khalifa General Hospital, Umm Al Quwain 499, United Arab Emirates"},{"name":"Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadira","family":"Al-baghli","sequence":"additional","affiliation":[{"name":"Directorate of Public Health, Dammam Network, Eastern Health Cluster, Dammam 31444, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-4513","authenticated-orcid":false,"given":"Saad","family":"Alhumaid","sequence":"additional","affiliation":[{"name":"Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1073\/pnas.91.6.2091","article-title":"Identification of Mycobacterium tuberculosis DNA in a Pre-Columbian Peruvian Mummy","volume":"91","author":"Salo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S1473-3099(04)01133-8","article-title":"Tuberculosis: From Prehistory to Robert Koch, as Revealed by Ancient DNA","volume":"4","author":"Donoghue","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.12264","article-title":"Co-evolution of Mycobacterium tuberculosis and Homo Sapiens","volume":"264","author":"Brites","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41423-020-0502-z","article-title":"New Insights into the Evasion of Host Innate Immunity by Mycobacterium tuberculosis","volume":"17","author":"Chai","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_5","unstructured":"World Health Organization (2022). Global Tuberculosis Report 2021: Supplementary Material, WHO."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chakaya, J., Petersen, E., Nantanda, R., Mungai, B.N., Migliori, G.B., Amanullah, F., Lungu, P., Ntoumi, F., Kumarasamy, N., and Maeurer, M. (2022). The WHO Global Tuberculosis 2021 Report\u2013Not so Good News and Turning the Tide Back to End TB. Int. J. Infect. Dis., in press.","DOI":"10.1016\/j.ijid.2022.03.011"},{"key":"ref_7","unstructured":"Wei, S., Yu-xian, S., Li-jie, Z., Shi-heng, X., Jing-tao, G., and Yu-hong, L. (2022). Tuberculosis Research and Innovation: Interpretation of the WHO Global Tuberculosis Report 2021. Chin. J. Antituberc., 44."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/S0140-6736(15)60570-0","article-title":"WHO\u2019s New End TB Strategy","volume":"385","author":"Uplekar","year":"2015","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2334-14-S1-S5","article-title":"Tuberculosis and HIV Co-Infection in Children","volume":"14","author":"Venturini","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S1473-3099(10)70139-0","article-title":"Best Drug Treatment for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis","volume":"10","author":"Caminero","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/jac\/dkr173","article-title":"Molecular Basis and Mechanisms of Drug Resistance in Mycobacterium tuberculosis: Classical and New Drugs","volume":"66","author":"Palomino","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pealing, L., Wing, K., Mathur, R., Prieto-Merino, D., Smeeth, L., and Moore, D.A.J. (2015). Risk of Tuberculosis in Patients with Diabetes: Population Based Cohort Study Using the UK Clinical Practice Research Datalink. BMC Med., 13.","DOI":"10.1186\/s12916-015-0381-9"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, X., Yang, Z., Fu, Y., Zhang, G., Wang, X., Zhang, Y., and Wang, X. (2014). Insight to the Epidemiology and Risk Factors of Extrapulmonary Tuberculosis in Tianjin, China during 2006\u20132011. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112213"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1183\/13993003.00432-2015","article-title":"Classification of Antituberculosis Drugs: A New Proposal Based on the Most Recent Evidence","volume":"46","author":"Caminero","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/jac\/dkl477","article-title":"Colorimetric Redox-Indicator Methods for the Rapid Detection of Multidrug Resistance in Mycobacterium tuberculosis: A Systematic Review and Meta-Analysis","volume":"59","author":"Martin","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/j.1365-3156.2010.02581.x","article-title":"Review of Multidrug-Resistant and Extensively Drug-Resistant TB: Global Perspectives with a Focus on Sub-Saharan Africa: Drug-Resistant TB","volume":"15","author":"Migliori","year":"2010","journal-title":"Trop. Med. Int. Health"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1378\/chest.08-2427","article-title":"Emergence of New Forms of Totally Drug-Resistant Tuberculosis Bacilli","volume":"136","author":"Velayati","year":"2009","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jgar.2017.10.006","article-title":"Drug-Resistant Mycobacterium tuberculosis: Epidemiology and Role of Morphological Alterations","volume":"12","author":"Velayati","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.coi.2015.06.001","article-title":"TB Vaccines; Promoting Rapid and Durable Protection in the Lung","volume":"35","author":"Andersen","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1007\/s00204-016-1727-6","article-title":"Antibiotic Resistance Mechanisms in M. tuberculosis: An Update","volume":"90","author":"Nguyen","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1111\/jam.14478","article-title":"Recent Updates on Drug Resistance in Mycobacterium tuberculosis","volume":"128","author":"Singh","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luthra, S., Rominski, A., and Sander, P. (2018). The Role of Antibiotic-Target-Modifying and Antibiotic-Modifying Enzymes in Mycobacterium Abscessus Drug Resistance. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02179"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Joshi, J. (2011). Tuberculosis Chemotherapy in the 21st Century: Back to the Basics. Lung India, 28.","DOI":"10.4103\/0970-2113.83977"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.micro.112408.134043","article-title":"Letting Sleeping Dos Lie: Does Dormancy Play a Role in Tuberculosis?","volume":"64","author":"Chao","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/jac\/dkt364","article-title":"Mutation Rate and the Emergence of Drug Resistance in Mycobacterium tuberculosis","volume":"69","author":"McGrath","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.3390\/ph5111210","article-title":"The Role of Transport Mechanisms in Mycobacterium tuberculosis Drug Resistance and Tolerance","volume":"5","author":"Sarathy","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1128\/AAC.02202-12","article-title":"Reduced Drug Uptake in Phenotypically Resistant Nutrient-Starved Nonreplicating Mycobacterium tuberculosis","volume":"57","author":"Sarathy","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sarathy, J.P., Via, L.E., Weiner, D., Blanc, L., Boshoff, H., Eugenin, E.A., Barry, C.E., and Dartois, V.A. (2018). Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02266-17"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1054\/tuld.1998.0200","article-title":"The Capsule of Mycobacterium tuberculosis and Its Implications for Pathogenicity","volume":"79","author":"Etienne","year":"1999","journal-title":"Tuber. Lung Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40265-014-0331-4","article-title":"Delamanid: A Review of Its Use in Patients with Multidrug-Resistant Tuberculosis","volume":"75","author":"Blair","year":"2015","journal-title":"Drugs"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, X.-Z., Elkins, C.A., and Zgurskaya, H.I. (2016). Efflux Pumps in Mycobacteria: Antimicrobial Resistance, Physiological Functions, and Role in Pathogenicity. Efflux-Mediated Antimicrobial Resistance in Bacteria, Springer International Publishing.","DOI":"10.1007\/978-3-319-39658-3"},{"key":"ref_32","first-page":"7","article-title":"What Do Proton Motive Force Driven Multidrug Resistance Transporters Have in Common?","volume":"7","author":"Mazurkiewicz","year":"2005","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ghajavand, H., Kargarpour Kamakoli, M., Khanipour, S., Pourazar Dizaji, S., Masoumi, M., Rahimi Jamnani, F., Fateh, A., Yaseri, M., Siadat, S.D., and Vaziri, F. (2019). Scrutinizing the Drug Resistance Mechanism of Multi- and Extensively-Drug Resistant Mycobacterium tuberculosis: Mutations versus Efflux Pumps. Antimicrob. Resist. Infect. Control, 8.","DOI":"10.1186\/s13756-019-0516-4"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yamamoto, K., Nakata, N., Mukai, T., Kawagishi, I., and Ato, M. (2021). Coexpression of MmpS5 and MmpL5 Contributes to Both Efflux Transporter MmpL5 Trimerization and Drug Resistance in Mycobacterium tuberculosis. mSphere, 6.","DOI":"10.1128\/mSphere.00518-20"},{"key":"ref_35","first-page":"E2510","article-title":"Identification of a Small Molecule with Activity against Drug-Resistant and Persistent Tuberculosis","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Seifert, M., Catanzaro, D., Catanzaro, A., and Rodwell, T.C. (2015). Genetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis: A Systematic Review. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119628"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Narang, A., Giri, A., Gupta, S., Garima, K., Bose, M., and Varma-Basil, M. (2017). Contribution of Putative Efflux Pump Genes to Isoniazid Resistance in Clinical Isolates of Mycobacterium tuberculosis. Int. J. Mycobacteriol., 6.","DOI":"10.4103\/ijmy.ijmy_26_17"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hameed, H.M.A., Islam, M.M., Chhotaray, C., Wang, C., Liu, Y., Tan, Y., Li, X., Tan, S., Delorme, V., and Yew, W.W. (2018). Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00114"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liu, J., Shi, W., Zhang, S., Hao, X., Maslov, D.A., Shur, K.V., Bekker, O.B., Danilenko, V.N., and Zhang, Y. (2019). Mutations in Efflux Pump Rv1258c (Tap) Cause Resistance to Pyrazinamide, Isoniazid, and Streptomycin in M. Tuberculosis. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00216"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/82_2012_279","article-title":"Molecular Biology of Drug Resistance in Mycobacterium tuberculosis","volume":"Volume 374","author":"Pieters","year":"2012","journal-title":"Pathogenesis of Mycobacterium tuberculosis and Its Interaction with the Host Organism"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11998","DOI":"10.1021\/bi701506h","article-title":"Irreversible Inhibition of the Mycobacterium tuberculosis \u03b2-Lactamase by Clavulanate","volume":"46","author":"Hugonnet","year":"2007","journal-title":"Biochemistry"},{"key":"ref_42","first-page":"1","article-title":"Nanotechnology-Based Approach in Tuberculosis Treatment","volume":"2017","author":"Nasiruddin","year":"2017","journal-title":"Tuberc. Res. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.4155\/fmc.13.80","article-title":"Strategies to Overcome the Action of Aminoglycoside-Modifying Enzymes for Treating Resistant Bacterial Infections","volume":"5","author":"Labby","year":"2013","journal-title":"Future Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.drup.2010.08.003","article-title":"Aminoglycoside Modifying Enzymes","volume":"13","author":"Ramirez","year":"2010","journal-title":"Drug Resist. Updates"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1021\/bi3004473","article-title":"Aminoglycoside Multiacetylating Activity of the Enhanced Intracellular Survival Protein from Mycobacterium smegmatis and Its Inhibition","volume":"51","author":"Chen","year":"2012","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/cbic.201300359","article-title":"Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis","volume":"14","author":"Houghton","year":"2013","journal-title":"ChemBioChem"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/femsre\/fux011","article-title":"Antimicrobial Resistance in Mycobacterium tuberculosis: Mechanistic and Evolutionary Perspectives","volume":"41","author":"Gygli","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20004","DOI":"10.1073\/pnas.0907925106","article-title":"Overexpression of the Chromosomally Encoded Aminoglycoside Acetyltransferase Eis Confers Kanamycin Resistance in Mycobacterium tuberculosis","volume":"106","author":"Zaunbrecher","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijmyco.2015.09.001","article-title":"Correlating Rrs and Eis Promoter Mutations in Clinical Isolates of Mycobacterium tuberculosis with Phenotypic Susceptibility Levels to the Second-Line Injectables","volume":"5","author":"Kambli","year":"2016","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Munita, J.M., and Arias, C.A. (2016). Mechanisms of Antibiotic Resistance. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.VMBF-0016-2015"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"981","DOI":"10.2174\/156802609789630947","article-title":"Quinolones: Action and Resistance Updated","volume":"9","author":"Drlica","year":"2009","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1093\/nar\/gks1351","article-title":"Mycobacterium Fluoroquinolone Resistance Protein B, a Novel Small GTPase, Is Involved in the Regulation of DNA Gyrase and Drug Resistance","volume":"41","author":"Tao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/emi.2014.17","article-title":"The Impact of Drug Resistance on Mycobacterium tuberculosis Physiology: What Can We Learn from Rifampicin?","volume":"3","author":"Koch","year":"2014","journal-title":"Emerg. Microbes Infect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2147\/IDR.S144446","article-title":"Diversity and Evolution of Drug Resistance Mechanisms in Mycobacterium tuberculosis","volume":"10","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/jac\/dkx506","article-title":"Evolution of Drug Resistance in Mycobacterium tuberculosis: A Review on the Molecular Determinants of Resistance and Implications for Personalized Care","volume":"73","author":"Dookie","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.tig.2011.05.007","article-title":"Molecular Mechanisms of Epistasis within and between Genes","volume":"27","author":"Lehner","year":"2011","journal-title":"Trends Genet."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Trindade, S., Sousa, A., Xavier, K.B., Dionisio, F., Ferreira, M.G., and Gordo, I. (2009). Positive Epistasis Drives the Acquisition of Multidrug Resistance. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000578"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1073\/pnas.95.7.3949","article-title":"Virulence of Antibiotic-Resistant Salmonella typhimurium","volume":"95","author":"Hughes","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1111\/j.1558-5646.2011.01302.x","article-title":"Epistasis Buffers the Fitness Effects of Rifampicin-Resistance Mutations in Pseudomonas aeruginosa: Buffering Epistasis Between Resistance Mutations","volume":"65","author":"Hall","year":"2011","journal-title":"Evolution"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/j.1420-9101.2009.01712.x","article-title":"The Cost of Multiple Drug Resistance in Pseudomonas aeruginosa","volume":"22","author":"Ward","year":"2009","journal-title":"J. Evol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3109\/10409239109114072","article-title":"DNA Gyrase: Structure and Function","volume":"26","author":"Reece","year":"1991","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1128\/AAC.38.4.805","article-title":"The RpoB Gene of Mycobacterium tuberculosis","volume":"38","author":"Miller","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","first-page":"2","article-title":"Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities","volume":"2","author":"Jacobs","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1054\/tuld.1998.0002","article-title":"Molecular Genetic Basis of Antimicrobial Agent Resistance in Mycobacterium tuberculosis: 1998 Update","volume":"79","author":"Ramaswamy","year":"1998","journal-title":"Tuber. Lung Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0022-2836(02)00463-1","article-title":"Crystal Structure of MabA from Mycobacterium tuberculosis, a Reductase Involved in Long-Chain Fatty Acid Biosynthesis","volume":"320","author":"Ducasse","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1126\/science.272.5268.1641","article-title":"Compensatory AhpC Gene Expression in Isoniazid-Resistant Mycobacterium tuberculosis","volume":"272","author":"Sherman","year":"1996","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1126\/science.280.5369.1607","article-title":"Inhibition of a Mycobacterium tuberculosis \u03b2-Ketoacyl ACP Synthase by Isoniazid","volume":"280","author":"Mdluli","year":"1998","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1128\/AAC.45.7.2157-2159.2001","article-title":"Novel Mutations in Ndh in Isoniazid-Resistant Mycobacterium tuberculosis Isolates","volume":"45","author":"Lee","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ijantimicag.2008.01.008","article-title":"Molecular Characterisation of Isoniazid-Resistant Mycobacterium tuberculosis Isolated from New Cases in Lagunes Region (C\u00f4te d\u2019Ivoire)","volume":"31","author":"Dosso","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lin, H.H., Kim, H.-Y., Yun, Y.-J., Park, C.G., Kim, B.-J., Park, Y.-G., and Kook, Y.-H. (2007). Mutations of katG and inhA in MDR M. tuberculosis. Tuberc. Respir. Dis., 63.","DOI":"10.4046\/trd.2007.63.2.128"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1086\/515362","article-title":"Mechanisms of Isoniazid Resistance in Mycobacterium tuberculosis: Enzymatic Characterization of Enoyl Reductase Mutants Identified in Isoniazid-Resistant Clinical Isolates","volume":"178","author":"Basso","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1128\/AAC.00112-06","article-title":"Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis","volume":"50","author":"Brimacombe","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1128\/AAC.47.4.1241-1250.2003","article-title":"Single Nucleotide Polymorphisms in Genes Associated with Isoniazid Resistance in Mycobacterium tuberculosis","volume":"47","author":"Ramaswamy","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1128\/JCM.01054-06","article-title":"Performance of the Genotype MTBDR Line Probe Assay for Detection of Resistance to Rifampin and Isoniazid in Strains of Mycobacterium tuberculosis with Low- and High-Level Resistance","volume":"44","author":"Brossier","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1128\/JCM.43.11.5477-5482.2005","article-title":"Detection of Mutations Associated with Isoniazid Resistance in Mycobacterium Tuberculosis Isolates from China","volume":"43","author":"Zhang","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1128\/AAC.00964-09","article-title":"Selection of Mutations to Detect Multidrug-Resistant Mycobacterium Tuberculosis Strains in Shanghai, China","volume":"54","author":"Luo","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1128\/AAC.48.9.3373-3381.2004","article-title":"Screening and Characterization of Mutations in Isoniazid-Resistant Mycobacterium tuberculosis Isolates Obtained in Brazil","volume":"48","author":"Cardoso","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1128\/JCM.02499-08","article-title":"Performance Assessment of the GenoType MTBDR plus Test and DNA Sequencing in Detection of Multidrug-Resistant Mycobacterium tuberculosis","volume":"47","author":"Huang","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4471","DOI":"10.1128\/JCM.41.9.4471-4474.2003","article-title":"Mutations in KatG, InhA, and AhpC Genes of Brazilian Isoniazid-Resistant Isolates of Mycobacterium tuberculosis","volume":"41","author":"Silva","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1099\/jmm.0.46718-0","article-title":"Molecular Characterization of Isoniazid-Resistant Clinical Isolates of Mycobacterium tuberculosis from the USA","volume":"55","author":"Guo","year":"2006","journal-title":"J. Med. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.diagmicrobio.2011.09.010","article-title":"Molecular Characterization of Drug-Resistant and -Susceptible Mycobacterium tuberculosis Isolated from Patients with Tuberculosis in Korea","volume":"72","author":"Yoon","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1128\/AAC.43.8.2087","article-title":"Contribution of KasA Analysis to Detection of Isoniazid-Resistant Mycobacterium tuberculosis in Singapore","volume":"43","author":"Lee","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1590\/S0074-02762007000100009","article-title":"Characterization of Ndh Gene of Isoniazid Resistant and Susceptible Mycobacterium tuberculosis Isolates from Brazil","volume":"102","author":"Cardoso","year":"2007","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1046\/j.1365-2958.2001.02427.x","article-title":"Regulation of Catalase-Peroxidase (KatG) Expression, Isoniazid Sensitivity and Virulence by FurA of Mycobacterium tuberculosis","volume":"40","author":"Pym","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lee, J.-H., Ammerman, N.C., Nolan, S., Geiman, D.E., Lun, S., Guo, H., and Bishai, W.R. (2012). Isoniazid Resistance without a Loss of Fitness in Mycobacterium tuberculosis. Nat. Commun., 3.","DOI":"10.1038\/ncomms1724"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1128\/AAC.00453-10","article-title":"Mycobacterium tuberculosis Dihydrofolate Reductase Is Not a Target Relevant to the Antitubercular Activity of Isoniazid","volume":"54","author":"Wang","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1093\/jac\/dkp292","article-title":"Isoniazid and Rifampicin Resistance-Associated Mutations in Mycobacterium tuberculosis Isolates from Yangon, Myanmar: Implications for Rapid Molecular Testing","volume":"64","author":"Valvatne","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1041.e1","DOI":"10.1016\/j.cmi.2018.12.008","article-title":"Detection of Novel Mutations Associated with Independent Resistance and Cross-Resistance to Isoniazid and Prothionamide in Mycobacterium tuberculosis Clinical Isolates","volume":"25","author":"Islam","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1054\/tuld.1999.0231","article-title":"Genomic Mutations in the KatG, InhA and AphC Genes Are Useful for the Prediction of Isoniazid Resistance in Mycobacterium tuberculosis Isolates from Kwazulu Natal, South Africa","volume":"80","author":"Kiepiela","year":"2000","journal-title":"Tuber. Lung Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1093\/jac\/dkm054","article-title":"Genetic and Phenotypic Characterization of Drug-Resistant Mycobacterium tuberculosis Isolates in Hong Kong","volume":"59","author":"Chan","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3201\/eid0402.980207","article-title":"Multidrug-Resistant Mycobacterium tuberculosis: Molecular Perspectives","volume":"4","author":"Rattan","year":"1998","journal-title":"Emerg. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/jac\/dkl058","article-title":"Rapid Detection of Specific Gene Mutations Associated with Isoniazid or Rifampicin Resistance in Mycobacterium tuberculosis Clinical Isolates Using Non-Fluorescent Low-Density DNA Microarrays","volume":"57","author":"Navarro","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng.1038","article-title":"Whole-Genome Sequencing of Rifampicin-Resistant Mycobacterium tuberculosis Strains Identifies Compensatory Mutations in RNA Polymerase Genes","volume":"44","author":"Comas","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/rr54","article-title":"The Molecular Basis of Resistance to Isoniazid, Rifampin, and Pyrazinamide in Mycobacterium tuberculosis","volume":"2","author":"Somoskovi","year":"2001","journal-title":"Respir. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1128\/JB.184.8.2167-2172.2002","article-title":"Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I","volume":"184","author":"Boshoff","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nm0696-662","article-title":"Mutations in PncA, a Gene Encoding Pyrazinamidase\/Nicotinamidase, Cause Resistance to the Antituberculous Drug Pyrazinamide in Tubercle Bacillus","volume":"2","author":"Scorpio","year":"1996","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1128\/AAC.33.9.1493","article-title":"Inhibition of Synthesis of Arabinogalactan by Ethambutol in Mycobacterium Smegmatis","volume":"33","author":"Takayama","year":"1989","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nm0597-567","article-title":"The Emb Operon, a Gene Cluster of Mycobacterium tuberculosis Involved in Resistance to Ethambutol","volume":"3","author":"Telenti","year":"1997","journal-title":"Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1128\/AAC.39.3.694","article-title":"Recognition of Multiple Effects of Ethambutol on Metabolism of Mycobacterial Cell Envelope","volume":"39","author":"Deng","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"48854","DOI":"10.1074\/jbc.M102272200","article-title":"The Role of the EmbA and EmbB Gene Products in the Biosynthesis of the Terminal Hexaarabinofuranosyl Motif of Mycobacterium smegmatis Arabinogalactan","volume":"276","author":"Escuyer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1128\/AAC.41.8.1677","article-title":"Ethambutol Resistance in Mycobacterium tuberculosis: Critical Role of EmbB Mutations","volume":"41","author":"Sreevatsan","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1128\/AAC.44.2.326-336.2000","article-title":"Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates of Mycobacterium tuberculosis","volume":"44","author":"Ramaswamy","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","first-page":"68","article-title":"Ethambutol Resistance Testing by Mutation Detection","volume":"10","author":"Johnson","year":"2006","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1128\/AAC.40.5.1186","article-title":"Characterization of Streptomycin Resistance Mechanisms among Mycobacterium tuberculosis Isolates from Patients in New York City","volume":"40","author":"Cooksey","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1128\/jcm.34.8.2007-2010.1996","article-title":"Identification of a Polymorphic Nucleotide in OxyR Specific for Mycobacterium Bovis","volume":"34","author":"Sreevatsan","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1128\/JCM.39.11.4184-4186.2001","article-title":"Sequence Polymorphism in the Rrs Gene of Mycobacterium tuberculosis Is Deeply Rooted within an Evolutionary Clade and Is Not Associated with Streptomycin Resistance","volume":"39","author":"Victor","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/35030019","article-title":"Functional Insights from the Structure of the 30S Ribosomal Subunit and Its Interactions with Antibiotics","volume":"407","author":"Carter","year":"2000","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1365-2958.1993.tb00924.x","article-title":"The RpsL Gene and Streptomycin Resistance in Single and Multiple Drug-Resistant Strains of Mycobacterium tuberculosis","volume":"10","author":"Nair","year":"1993","journal-title":"Mol. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/j.1365-2958.2006.05585.x","article-title":"Loss of a Conserved 7-Methylguanosine Modification in 16S RRNA Confers Low-Level Streptomycin Resistance in Bacteria","volume":"63","author":"Okamoto","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1128\/AAC.01570-07","article-title":"Identification of Mutations Related to Streptomycin Resistance in Clinical Isolates of Mycobacterium tuberculosis and Possible Involvement of Efflux Mechanism","volume":"52","author":"Spies","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"D1091","DOI":"10.1093\/nar\/gkt1068","article-title":"DrugBank 4.0: Shedding New Light on Drug Metabolism","volume":"42","author":"Law","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1089\/mdr.2006.12.7","article-title":"Stepwise Decrease in Moxifloxacin Susceptibility amongst Clinical Isolates of Multidrug-Resistant Mycobacterium tuberculosis: Correlation with Ofloxacin Susceptibility","volume":"12","author":"Kam","year":"2006","journal-title":"Microb. Drug Resist."},{"key":"ref_113","first-page":"1320","article-title":"Mechanisms of Drug Resistance in Mycobacterium tuberculosis","volume":"13","author":"Zhang","year":"2009","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1126\/science.1110699","article-title":"A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA","volume":"308","author":"Hegde","year":"2005","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1128\/JCM.36.5.1220-1225.1998","article-title":"Detection of Kanamycin-Resistant Mycobacterium tuberculosis by Identifying Mutations in the 16S RRNA Gene","volume":"36","author":"Suzuki","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_116","first-page":"344","article-title":"InhA Promoter Mutations: A Gateway to Extensively Drug-Resistant Tuberculosis in South Africa?","volume":"15","author":"Streicher","year":"2011","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1128\/AAC.01030-10","article-title":"Molecular Investigation of Resistance to the Antituberculous Drug Ethionamide in Multidrug-Resistant Clinical Isolates of Mycobacterium tuberculosis","volume":"55","author":"Brossier","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1128\/AAC.47.12.3799-3805.2003","article-title":"EthA, InhA, and KatG Loci of Ethionamide-Resistant Clinical Mycobacterium tuberculosis Isolates","volume":"47","author":"Morlock","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1073\/pnas.97.17.9677","article-title":"Ethionamide Activation and Sensitivity in Multidrug-Resistant Mycobacterium tuberculosis","volume":"97","author":"DeBarber","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1111\/j.1365-2672.2010.04840.x","article-title":"Usefulness of Resistant Gene Markers for Predicting Treatment Outcome on Second-Line Anti-Tuberculosis Drugs","volume":"109","author":"Leung","year":"2010","journal-title":"J. Appl. Microbiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/j.1469-0691.2009.02838.x","article-title":"Genotypic Analysis of Genes Associated with Isoniazid and Ethionamide Resistance in MDR-TB Isolates from Thailand","volume":"16","author":"Boonaiam","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1128\/jcm.18.3.689-696.1983","article-title":"Evaluation of the BACTEC Radiometric Method for Recovery of Mycobacteria and Drug Susceptibility Testing of Mycobacterium tuberculosis from Acid-Fast Smear-Positive Specimens","volume":"18","author":"Roberts","year":"1983","journal-title":"J. Clin. Microbiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1128\/JCM.37.10.3179-3186.1999","article-title":"Multicenter Laboratory Validation of Susceptibility Testing of Mycobacterium tuberculosis against Classical Second-Line and Newer Antimicrobial Drugs by Using the Radiometric BACTEC 460 Technique and the Proportion Method with Solid Media","volume":"37","author":"Pfyffer","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3390\/antibiotics3030317","article-title":"Drug Resistance Mechanisms in Mycobacterium tuberculosis","volume":"3","author":"Palomino","year":"2014","journal-title":"Antibiotics"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/JCM.36.5.1214-1219.1998","article-title":"Use of 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyl Tetrazolium Bromide for Rapid Detection of Rifampin-Resistant Mycobacterium tuberculosis","volume":"36","author":"Mshana","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.tube.2006.07.005","article-title":"Modern Approaches to a Rapid Diagnosis of Tuberculosis: Promises and Challenges Ahead","volume":"87","author":"Tiwari","year":"2007","journal-title":"Tuberculosis"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1128\/JCM.39.2.651-657.2001","article-title":"Comparison of MB\/BacT ALERT 3D System with Radiometric BACTEC System and L\u00f6wenstein-Jensen Medium for Recovery and Identification of Mycobacteria from Clinical Specimens: A Multicenter Study","volume":"39","author":"Piersimoni","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/PL00015025","article-title":"Simple Procedure for Drug Susceptibility Testing of Mycobacterium tuberculosis Using a Commercial Colorimetic Assay","volume":"18","author":"Palomino","year":"1999","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1586\/ers.09.45","article-title":"Drug-Susceptibility Testing in TB: Current Status and Future Prospects","volume":"3","author":"Richter","year":"2009","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1128\/jcm.35.1.121-124.1997","article-title":"Clinical Evaluation of Difco ESP Culture System II for Growth and Detection of Mycobacteria","volume":"35","author":"Woods","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1093\/jac\/dkp096","article-title":"Fluoroquinolone Resistance in Mycobacterium tuberculosis: An Assessment of MGIT 960, MODS and Nitrate Reductase Assay and Fluoroquinolone Cross-Resistance","volume":"63","author":"Devasia","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1056\/NEJMoa055524","article-title":"Microscopic-Observation Drug-Susceptibility Assay for the Diagnosis of TB","volume":"355","author":"Moore","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1128\/jcm.33.9.2324-2327.1995","article-title":"Colorimetric Method for Determining MICs of Antimicrobial Agents for Mycobacterium tuberculosis","volume":"33","author":"Yajko","year":"1995","journal-title":"J. Clin. Microbiol."},{"key":"ref_135","first-page":"1118","article-title":"Rapid and Simple MTT Method for Rifampicin and Isoniazid Susceptibility Testing of Mycobacterium tuberculosis","volume":"6","author":"Foongladda","year":"2002","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nm0497-465","article-title":"Evaluation of a New Rapid Bacteriophage-Based Method for the Drug Susceptibility Testing of Mycobacterium tuberculosis","volume":"3","author":"Wilson","year":"1997","journal-title":"Nat. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1385\/1-59259-147-7:145","article-title":"Phage Replication Technology for Diagnosis and Drug Susceptibility Testing","volume":"Volume 54","author":"McNerney","year":"2001","journal-title":"Mycobacterium tuberculosis Protocols"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1099\/jmm.0.05149-0","article-title":"Rapid Identification and Susceptibility Testing of Mycobacterium tuberculosis from MGIT Cultures with Luciferase Reporter Mycobacteriophages","volume":"52","author":"Banaiee","year":"2003","journal-title":"J. Med. Microbiol."},{"key":"ref_139","first-page":"138","article-title":"Microcolony Detection in 7H11 Thin Layer Culture Is an Alternative for Rapid Diagnosis of Mycobacterium tuberculosis Infection","volume":"3","author":"Mejia","year":"1999","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_140","first-page":"751","article-title":"E-Test for Susceptibility Testing of Mycobacterium tuberculosis","volume":"2","author":"Hausdorfer","year":"1998","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.mimet.2008.06.015","article-title":"Rapid Culture-Based Methods for Drug-Resistance Detection in Mycobacterium tuberculosis","volume":"75","author":"Palomino","year":"2008","journal-title":"J. Microbiol. Methods"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ijmyco.2015.04.005","article-title":"Drug Susceptibility Testing of Mycobacterium tuberculosis by a Nitrate Reductase Assay Applied Directly on Microscopy-Positive Sputum Samples","volume":"4","author":"Kammoun","year":"2015","journal-title":"Int. J. Mycobacteriology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3329\/jhpn.v29i1.7563","article-title":"Evaluation of the Performance of Nitrate Reductase Assay for Rapid Drug-Susceptibility Testing of Mycobacterium tuberculosis in North India","volume":"29","author":"Gupta","year":"2011","journal-title":"J. Health Popul. Nutr."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3855\/jidc.1079","article-title":"Direct Drug Susceptibility Testing of Mycobacterium tuberculosis against Primary Anti-TB Drugs in Northern India","volume":"4","author":"Gupta","year":"2010","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1128\/JCM.40.2.553-555.2002","article-title":"Rapid and Inexpensive Drug Susceptibility Testing of Mycobacterium tuberculosis with a Nitrate Reductase Assay","volume":"40","author":"Klintz","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1128\/JCM.39.7.2642-2645.2001","article-title":"Mycolic Acid Index Susceptibility Method for Mycobacterium tuberculosis","volume":"39","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1128\/jcm.35.5.1287-1289.1997","article-title":"Determination of Drug Susceptibility of Mycobacterium tuberculosis through Mycolic Acid Analysis","volume":"35","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_148","first-page":"859","article-title":"Routine Rapid Mycobacterium Species Assignment Based on Species-Specific Allelic Variation in the 65-Kilodalton Heat Shock Protein Gene (Hsp65)","volume":"121","author":"Pai","year":"1997","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1385\/1-59259-147-7:155","article-title":"Detection of Mutations in Mycobacterium tuberculosis by a Dot Blot Hybridization Strategy","volume":"Volume 54","author":"Victor","year":"2001","journal-title":"Mycobacterium tuberculosis Protocols"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2217\/17460913.3.2.111","article-title":"XDR-TB Genome Sequencing: A Glimpse of the Microbiology of the Future","volume":"3","author":"Loman","year":"2008","journal-title":"Future Microbiol."},{"key":"ref_151","first-page":"328","article-title":"Development of a Pyrosequencing Approach for Rapid Screening of Rifampin, Isoniazid and Ethambutol-Resistant Mycobacterium tuberculosis","volume":"9","author":"Zhao","year":"2005","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1128\/JCM.02210-05","article-title":"Rapid Detection of Rifampin Resistance in Mycobacterium tuberculosis by Pyrosequencing Technology","volume":"44","author":"Jureen","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1128\/JCM.01229-09","article-title":"Pyrosequencing for Rapid Detection of Mycobacterium tuberculosis Resistance to Rifampin, Isoniazid, and Fluoroquinolones","volume":"47","author":"Bravo","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1128\/JCM.00439-06","article-title":"Evaluation of the TB-Biochip Oligonucleotide Microarray System for Rapid Detection of Rifampin Resistance in Mycobacterium tuberculosis","volume":"44","author":"Caoili","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cmi.2017.11.001","article-title":"Practical Issues in Implementing Whole-Genome-Sequencing in Routine Diagnostic Microbiology","volume":"24","author":"Rossen","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cmi.2017.10.013","article-title":"Next-Generation Sequencing Technologies and Their Application to the Study and Control of Bacterial Infections","volume":"24","author":"Besser","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"731.e9","DOI":"10.1016\/j.cmi.2021.09.014","article-title":"Whole-Genome Sequencing for Surveillance of Tuberculosis Drug Resistance and Determination of Resistance Level in China","volume":"28","author":"Liu","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.diagmicrobio.2005.06.007","article-title":"Simultaneous Detection of Isoniazid, Rifampin, and Ethambutol Resistance of Mycobacterium tuberculosis by a Single Multiplex Allele-Specific Polymerase Chain Reaction (PCR) Assay","volume":"53","author":"Yang","year":"2005","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1093\/jac\/dkq047","article-title":"Novel Multiplex Allele-Specific PCR Assays for the Detection of Resistance to Second-Line Drugs in Mycobacterium tuberculosis","volume":"65","author":"Evans","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/jcla.21558","article-title":"Rapid Genotypic Detection of RpoB and KatG Gene Mutations in Mycobacterium tuberculosis Clinical Isolates from Northern India as Determined by MAS-PCR: Detection of RpoB and KatG Mutations by MAS-PCR","volume":"27","author":"Gupta","year":"2013","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1469-0691.2005.01183.x","article-title":"Evaluation of Hybridisation on Oligonucleotide Microarrays for Analysis of Drug-Resistant Mycobacterium tuberculosis","volume":"11","author":"Gryadunov","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1128\/AAC.37.10.2054","article-title":"Direct, Automated Detection of Rifampin-Resistant Mycobacterium tuberculosis by Polymerase Chain Reaction and Single-Strand Conformation Polymorphism Analysis","volume":"37","author":"Telenti","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1086\/516313","article-title":"Evaluation of a Polymerase Chain Reaction\u2013Based Universal Heteroduplex Generator Assay for Direct Detection of Rifampin Susceptibility of Mycobacterium tuberculosis from Sputum Specimens","volume":"26","author":"Williams","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.mimet.2010.11.014","article-title":"Tuberculosis Drug Resistance Testing by Molecular Methods: Opportunities and Challenges in Resource Limited Settings","volume":"84","author":"Abebe","year":"2011","journal-title":"J. Microbiol. Methods"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s10517-008-0034-5","article-title":"Detection of Mutations in Mycobacterium tuberculosis Genome Determining Resistance to Fluoroquinolones by Hybridization on Biological Microchips","volume":"145","author":"Antonova","year":"2008","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1128\/JCM.43.8.3699-3703.2005","article-title":"Use of the Genotype MTBDR Assay for Rapid Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Complex Isolates","volume":"43","author":"Hillemann","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_167","first-page":"1057","article-title":"Application of the Genotype MTBDR Assay Directly on Sputum Specimens","volume":"10","author":"Hillemann","year":"2006","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Huyen, M.N., Tiemersma, E.W., Lan, N.T., Cobelens, F.G., Dung, N.H., Sy, D.N., Buu, T.N., Kremer, K., Hang, P.T., and Caws, M. (2010). Validation of the GenoType\u00aeMTBDRplus Assay for Diagnosis of Multidrug Resistant Tuberculosis in South Vietnam. BMC Infect. Dis., 10.","DOI":"10.1186\/1471-2334-10-149"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1128\/JCM.00081-09","article-title":"Feasibility of the GenoType MTBDR Sl Assay for Fluoroquinolone, Amikacin-Capreomycin, and Ethambutol Resistance Testing of Mycobacterium tuberculosis Strains and Clinical Specimens","volume":"47","author":"Hillemann","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3164\/jcbn.2008033","article-title":"Five-Antituberculosis Drug-Resistance Genes Detection Using Array System","volume":"42","author":"Shimizu","year":"2008","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1128\/AAC.46.5.1417-1424.2002","article-title":"High Prevalence of KatG Ser315Thr Substitution among Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates from Northwestern Russia, 1996 to 2001","volume":"46","author":"Mokrousov","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1099\/jmm.0.05223-0","article-title":"Detection of KatG Ser315Thr Substitution in Respiratory Specimens from Patients with Isoniazid-Resistant Mycobacterium tuberculosis Using PCR-RFLP","volume":"52","author":"Leung","year":"2003","journal-title":"J. Med. Microbiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1128\/AAC.49.1.144-147.2005","article-title":"New Multiplex PCR for Rapid Detection of Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates","volume":"49","author":"Molina","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1128\/jcm.33.12.3225-3233.1995","article-title":"PCR Assay Based on DNA Coding for 16S RRNA for Detection and Identification of Mycobacteria in Clinical Samples","volume":"33","author":"Kox","year":"1995","journal-title":"J. Clin. Microbiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.mimet.2005.03.002","article-title":"Comparison of Drug Resistance Genotypes between Beijing and Non-Beijing Family Strains of Mycobacterium tuberculosis in Korea","volume":"63","author":"Park","year":"2005","journal-title":"J. Microbiol. Methods"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Notomi, T. (2000). Loop-Mediated Isothermal Amplification of DNA. Nucleic Acids Res., 28.","DOI":"10.1093\/nar\/28.12.e63"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1128\/JCM.02352-06","article-title":"Operational Feasibility of Using Loop-Mediated Isothermal Amplification for Diagnosis of Pulmonary Tuberculosis in Microscopy Centers of Developing Countries","volume":"45","author":"Boehme","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2217\/fmb.11.84","article-title":"Xpert \u00ae MTB\/RIF Assay: Development, Evaluation and Implementation of a New Rapid Molecular Diagnostic for Tuberculosis and Rifampicin Resistance","volume":"6","author":"Lawn","year":"2011","journal-title":"Future Microbiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1128\/JCM.01463-09","article-title":"Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology","volume":"48","author":"Helb","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1164\/rccm.201510-2091OC","article-title":"Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value","volume":"194","author":"Farhat","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ng.2735","article-title":"Genome Sequencing of 161 Mycobacterium tuberculosis Isolates from China Identifies Genes and Intergenic Regions Associated with Drug Resistance","volume":"45","author":"Zhang","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/bioinformatics\/btx801","article-title":"Machine Learning for Classifying Tuberculosis Drug-Resistance from DNA Sequencing Data","volume":"34","author":"Yang","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Jamal, S., Khubaib, M., Gangwar, R., Grover, S., Grover, A., and Hasnain, S.E. (2020). Artificial Intelligence and Machine Learning Based Prediction of Resistant and Susceptible Mutations in Mycobacterium tuberculosis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62368-2"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Borisov, S.E., Dheda, K., Enwerem, M., Romero Leyet, R., D\u2019Ambrosio, L., Centis, R., Sotgiu, G., Tiberi, S., Alffenaar, J.-W., and Maryandyshev, A. (2017). Effectiveness and Safety of Bedaquiline-Containing Regimens in the Treatment of MDR- and XDR-TB: A Multicentre Study. Eur. Respir. J., 49.","DOI":"10.1183\/13993003.00387-2017"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1183\/09031936.00125812","article-title":"Delamanid Improves Outcomes and Reduces Mortality in Multidrug-Resistant Tuberculosis","volume":"41","author":"Skripconoka","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Hafkin, J., Hittel, N., Martin, A., and Gupta, R. (2017). Early Outcomes in MDR-TB and XDR-TB Patients Treated with Delamanid under Compassionate Use. Eur. Respir. J., 50.","DOI":"10.1183\/13993003.00311-2017"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"305","DOI":"10.5588\/ijtld.20.0513","article-title":"A Partially Randomised Trial of Pretomanid, Moxifloxacin and Pyrazinamide for Pulmonary TB","volume":"25","author":"Tweed","year":"2021","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/trstmh\/trv107","article-title":"Management of Multidrug-Resistant TB: Novel Treatments and Their Expansion to Low Resource Settings","volume":"110","author":"Sloan","year":"2016","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3897\/folmed.62.e48742","article-title":"Linezolid: A Promising Agent for the Treatment of Multiple and Extensively Drug-Resistant Tuberculosis","volume":"62","author":"Fermeli","year":"2020","journal-title":"Folia Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1080\/14787210.2016.1225498","article-title":"Linezolid in the Treatment of Drug-Resistant Tuberculosis: The Challenge of Its Narrow Therapeutic Index","volume":"14","author":"Wasserman","year":"2016","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ijid.2019.04.028","article-title":"Linezolid Interruption in Patients with Fluoroquinolone-Resistant Tuberculosis Receiving a Bedaquiline-Based Treatment Regimen","volume":"85","author":"Olayanju","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/1791013a0","article-title":"A New Series of Phenazines (Rimino-Compounds) With High Antituberculosis Activity","volume":"179","author":"Barry","year":"1957","journal-title":"Nature"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1128\/AAC.36.12.2729","article-title":"Antimicrobial Activities of Clofazimine and B669 Are Mediated by Lysophospholipids","volume":"36","author":"Anderson","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1128\/AAC.00395-15","article-title":"Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis","volume":"59","author":"Lechartier","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"10276","DOI":"10.1074\/jbc.M110.200501","article-title":"Reduction of Clofazimine by Mycobacterial Type 2 NADH: Quinone Oxidoreductase","volume":"286","author":"Yano","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/jac\/43.5.615","article-title":"Antimycobacterial Activities of Riminophenazines","volume":"43","author":"Reddy","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000007255","article-title":"In Vitro Investigation of the Antimicrobial Activities of Novel Tetramethylpiperidine- Substituted Phenazines against Mycobacterium tuberculosis","volume":"46","author":"Sirgel","year":"2000","journal-title":"Chemotherapy"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1164\/rccm.201410-1801OC","article-title":"Bactericidal Activity of Pyrazinamide and Clofazimine Alone and in Combinations with Pretomanid and Bedaquiline","volume":"191","author":"Diacon","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1093\/jac\/dkx022","article-title":"For the Global PETTS Investigators Susceptibilities of MDR Mycobacterium tuberculosis Isolates to Unconventional Drugs Compared with Their Reported Pharmacokinetic\/Pharmacodynamic Parameters","volume":"72","author":"Cavanaugh","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.5588\/ijtld.12.0144","article-title":"Systematic Review of Clofazimine for the Treatment of Drug-Resistant Tuberculosis [Review Article]","volume":"17","author":"Gopal","year":"2013","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0140-6736(18)31644-1","article-title":"Treatment Correlates of Successful Outcomes in Pulmonary Multidrug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis","volume":"392","author":"Ahmad","year":"2018","journal-title":"Lancet"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1046\/j.1472-765X.2002.01201.x","article-title":"Preparation of Microparticulate Beta-Glucan from Saccharomyces Cerevisiae for Use in Immune Potentiation","volume":"35","author":"Hunter","year":"2002","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.carres.2011.03.038","article-title":"Probing \u03b2-(1\u21923)-d-Glucans Interactions with Recombinant Human Receptors Using High-Resolution NMR Studies","volume":"346","author":"Sylla","year":"2011","journal-title":"Carbohydr. Res."},{"key":"ref_204","unstructured":"Upadhyay, T.K., Fatima, N., Sharma, D., Saravanakumar, V., and Sharma, R. (2017). Preparation and Characterization of Beta-Glucan Particles Containing a Payload of Nanoembedded Rifabutin for Enhanced Targeted Delivery to Macrophages. EXCLI J., 16."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3390\/polym2040681","article-title":"Glucan Particle Encapsulated Rifampicin for Targeted Delivery to Macrophages","volume":"2","author":"Soto","year":"2010","journal-title":"Polymers"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/nature07774","article-title":"Orally Delivered SiRNA Targeting Macrophage Map4k4 Suppresses Systemic Inflammation","volume":"458","author":"Aouadi","year":"2009","journal-title":"Nature"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1021\/bc700329p","article-title":"Characterization of Multilayered Nanoparticles Encapsulated in Yeast Cell Wall Particles for DNA Delivery","volume":"19","author":"Soto","year":"2008","journal-title":"Bioconj. Chem."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Hong, Z., Yu, M., Chen, Z., Guo, W., Wang, J., Feng, Y., and Kong, X. (2015). Specifically Targeted Delivery of Protein to Phagocytic Macrophages. Int. J. Nanomed., 10.","DOI":"10.2147\/IJN.S75950"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/21691401.2018.1559180","article-title":"Nano-Rifabutin Entrapment within Glucan Microparticles Enhances Protection against Intracellular Mycobacterium tuberculosis","volume":"47","author":"Upadhyay","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Fatima, N., Upadhyay, T., Ahmad, F., Arshad, M., Kamal, M.A., Sharma, D., and Sharma, R. (2021). Particulate \u03b2-Glucan Activates Early and Delayed Phagosomal Maturation and Autophagy within Macrophage in a NOX-2 Dependent Manner. Life Sci., 266.","DOI":"10.1016\/j.lfs.2020.118851"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:06Z","timestamp":1760144166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":210,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27206985"],"URL":"https:\/\/doi.org\/10.3390\/molecules27206985","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}