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The Challenge of Drug-Resistant Tuberculosis: An Update

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Pathogenicity and Drug Resistance of Human Pathogens

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Abstract

Tuberculosis (TB) is one of the leading causes of death from a single infectious agent, and millions of people fall sick due to this disease every year. In spite of effective treatment, drug-resistant tuberculosis is a major problem worldwide. Globally, 3.5% of new cases and 18% of previously treated cases were estimated to have MDR-TB in 2017. Among these, 8.5% cases were estimated to have XDR-TB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are, thus, responsible for significant obstruction to global TB control. Drug resistance in M. tuberculosis primarily occurs through chromosomal mutations in genes encoding for drug target or drug-activating enzymes. However, alternative mechanisms, such as membrane impermeability, drug inactivation or modification by enzymes, and efflux pumps, may also be responsible for drug resistance. Insight into the mechanisms of drug resistance would help mankind in limiting the disease through the use and development of better diagnostic and therapeutic tools. Here we describe the prevalence of drug resistance in M. tuberculosis, the mechanisms of drug resistance, and the rapid diagnostic assays currently available to detect drug-resistant M. tuberculosis.

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References

  1. Almeida, D., Ioerger, T., Tyagi, S., et al. (2016). Mutations in pepQ confer low-level resistance to bedaquiline and clofazimine in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 60, 4590–4599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aubry, A., Pan, X. S., Fisher, L. M., et al. (2004). Mycobacterium tuberculosis DNA gyrase: Interaction with quinolones and correlation with antimycobacterial drug activity. Antimicrobial Agents and Chemotherapy, 48, 1281–1288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Barry, C. E., 3rd, Lee, R. E., Mdluli, K., et al. (1998). Mycolic acids: Structure, biosynthesis and physiological functions. Progress in Lipid Research, 37, 143.

    Article  CAS  PubMed  Google Scholar 

  4. Brauner, A., Fridman, O., Gefen, O., et al. (2016). Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nature Reviews. Microbiology, 14, 320–330.

    Article  CAS  PubMed  Google Scholar 

  5. Brennan, P. J., & Nikaido, H. (1995). The envelope of mycobacteria. Annual Review of Biochemistry, 64, 29–63.

    Article  CAS  PubMed  Google Scholar 

  6. Bwanga, F., Hoffner, S., Haile, M., et al. (2009). Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis. BMC Infectious Diseases, 9, 67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Canetti, G., Fox, W., Khomenko, A. A., et al. (1969). Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bulletin of the World Health Organization, 41, 21.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Carter, A. P., Clemons, W. M., Brodersen, D. E., et al. (2000). Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature, 407, 340–348.

    Article  CAS  PubMed  Google Scholar 

  9. Cavusoglu, C., Hilmioglu, S., Guneri, S., et al. (2002). Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. Journal of Clinical Microbiology, 40, 4435–4438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chakravorty, S., Simmons, A. M., & Parmar, R. M. (2017). The new Xpert MTB/RIF ultra: Improving detection of Mycobacterium tuberculosis and resistance to rifampin in an assay suitable for point-of-care testing. MBio, 8, e00812–e00817.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cheng, S. J., Thibert, L., Sanchez, T., et al. (2000). pncA mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: Spread of a monoresistant strain in Quebec. Canada. Antimicrob Agents Chemother, 44, 528–532.

    Article  CAS  PubMed  Google Scholar 

  12. Cheng, A. F., Yew, W. W., Chan, E. W., et al. (2004). Multiplex PCR amplimer conformation analysis for rapid detection of gyrA mutations in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates. Antimicrobial Agents and Chemotherapy, 48, 596–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Coban, A. Y., Birinci, A., Ekinci, B., et al. (2004). Drug susceptibility testing of Mycobacterium tuberculosis with nitrate reductase assay. International Journal of Antimicrobial Agents, 24, 304–306.

    Article  CAS  PubMed  Google Scholar 

  14. Das, R., Gupta, P., Singh, P., et al. (2009). Association of mutations in rpsL gene with high degree of streptomycin resistance in clinical isolates of Mycobacterium tuberculosis in India. The Indian Journal of Medical Research, 129, 108–111.

    CAS  PubMed  Google Scholar 

  15. Desjardins, C. A., Cohen, K. A., Munsamy, V., et al. (2016). Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance. Nature Genetics, 48, 544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dey, T., Brigden, G., Cox, H., et al. (2013). Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: A systematic review and meta-analysis. The Journal of Antimicrobial Chemotherapy, 68, 284–293.

    Article  CAS  PubMed  Google Scholar 

  17. Dookie, N., Rambaran, S., Padayatchi, N., Mahomed, S., & Naidoo, K. (2018). Evolution of drug resistance in Mycobacterium tuberculosis. The Journal of Antimicrobial Chemotherapy, 73, 1138–1151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Drlica, K. (1999). Mechanism of fluoroquinolone action. Current Opinion in Microbiology, 2, 504–508.

    Article  CAS  PubMed  Google Scholar 

  19. Drobniewski, F., Rüsch-Gerdes, S., & Hoffner, S. (2007). Antimicrobial susceptibility testing of Mycobacterium tuberculosis (EUCAST document E. DEF 8.1)–report of the subcommittee on antimicrobial susceptibility testing of Mycobacterium tuberculosis of the European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Clinical Microbiology and Infection, 13, 1144–1156.

    Article  CAS  PubMed  Google Scholar 

  20. Duque, A., Lin, S. Y. G., Desmond, E., et al. (2013). Evaluation of the BD Bactec MGIT 320 system for detection of mycobacteria and drug susceptibility testing of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 51, 3403–3405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Eldholm, V., Norheim, G., von der Lippe, B., et al. (2014). Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient. Genome Biology, 15, 490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Escalante, P., Ramaswamy, S., Sanabria, H., et al. (1998). Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru. Tubercle and Lung Disease, 79, 111–118.

    Article  CAS  PubMed  Google Scholar 

  23. Faustini, A., Hall, A. J., & Perucci, C. A. (2006). Risk factors for multidrug resistant tuberculosis in Europe: A systematic review. Thorax, 61, 158–163.

    Article  CAS  PubMed  Google Scholar 

  24. Feng, Z., & Barletta, R. G. (2003). Roles of Mycobacterium smegmatis D-alanine: D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrobial Agents and Chemotherapy, 47, 283–291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Feuerriegel, S., Köser, C., Trübe, L., et al. (2010). Thr202Ala in thyA is a marker for the Latin American Mediterranean lineage of the Mycobacterium tuberculosis complex rather than para-aminosalicylic acid resistance. Antimicrobial Agents and Chemotherapy, 54, 4794–4798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Finken, M., Kirschner, P., Meier, A., et al. (1993). Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: Alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. Molecular Microbiology, 9, 1239–1246.

    Article  CAS  PubMed  Google Scholar 

  27. Ginsburg, A. S., Grosset, J. H., & Bishai, W. R. (2003). Fluoroquinolones, tuberculosis, and resistance. Lancet Infectious Diseases, 3, 432–442.

    Article  CAS  PubMed  Google Scholar 

  28. Grange, J. M. (1990). Drug resistance and tuberculosis elimination. Bulletin of the International Union against Tuberculosis and Lung Disease, 65, 57.

    CAS  PubMed  Google Scholar 

  29. Hartkoorn, R. C., Uplekar, S., & Cole, S. T. (2014). Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 58, 2979–2981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hazbon, M. H., Brimacombe, M., Bobadilla del Valle, M., et al. (2006). Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 50, 2640–2649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Helb, D., Jones, M., Story, E., et al. (2010). Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. Journal of Clinical Microbiology, 48, 229–237.

    Article  CAS  PubMed  Google Scholar 

  32. Herrera, L., Jiménez, S., Valverde, A., et al. (2003). Molecular analysis of rifampicin-resistant Mycobacterium tuberculosis isolated in Spain (1996–2001). Description of new mutations in the rpoB gene and review of the literature. International Journal of Antimicrobial Agents, 21, 403–408.

    Article  CAS  PubMed  Google Scholar 

  33. Heym, B., & Cole, S. T. (1997). Multidrug resistance in Mycobacterium tuberculosis. International Journal of Antimicrobial Agents, 8, 61–70.

    Article  CAS  PubMed  Google Scholar 

  34. Hoagland, D. T., Liu, J., Lee, R. B., et al. (2016). New agents for the treatment of drug-resistant Mycobacterium tuberculosis. Advanced Drug Delivery Reviews, 102, 55–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Horne, D. J., Pinto, L. M., Arentz, M., et al. (2013). Diagnostic accuracy and reproducibility of WHO-endorsed phenotypic drug susceptibility testing methods for first-line and second-line anti-TB drugs. Journal of Clinical Microbiology, 51, 393–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ismail, N. A., Omar, S. V., Joseph, L., et al. (2018). Defining bedaquiline susceptibility, resistance, cross-resistance and associated genetic determinants: A retrospective cohort study. E BioMedicine, 28, 136–142.

    Google Scholar 

  37. Jenkins, H. E., Zignol, M., & Cohen, T. (2011). Quantifying the burden and trends of isoniazid resistant tuberculosis, 1994–2009. PLoS One, 6, e22927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jia, L., Tomaszewski, J. E., Hanrahan, C., et al. (2005). Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug. British Journal of Pharmacology, 144, 80–87.

    Article  CAS  PubMed  Google Scholar 

  39. Juréen, P., Werngren, J., Toro, J.-C., et al. (2008). Pyrazinamide resistance and pncA gene mutations in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 52, 1852–1854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kaur, S., Rana, V., Singh, P., et al. (2016). Novel mutations conferring resistance to kanamycin in Mycobacterium tuberculosis clinical isolates from northern India. Tuberculosis, 96, 96–101.

    Article  CAS  PubMed  Google Scholar 

  41. Köser, C. U., Bryant, J. M., Becq, J., et al. (2013). Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis. The New England Journal of Medicine, 369, 290–292.

    Article  CAS  PubMed  Google Scholar 

  42. Koch, A., Cox, H., & Mizrahi, V. (2018). Drug-resistant tuberculosis: Challenges and opportunities for diagnosis and treatment. Current Opinion in Pharmacology, 42, 7–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lakshminarayana, S. B., Huat, T. B., Ho, P. C., et al. (2014). Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents. The Journal of Antimicrobial Chemotherapy, 70, 857–867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lange, C., Chesov, D., Heyckendorf, J., et al. (2018). Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment. Respirology, 23, 656–673.

    Article  PubMed  Google Scholar 

  45. Larsen, M. H., Vilcheze, C., Kremer, L., et al. (2002). Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Molecular Microbiology, 46, 453–466.

    Article  PubMed  Google Scholar 

  46. Lemus, D., Montoro, E., Echemendía, M., et al. (2006). Nitrate reductase assay for detection of drug resistance in Mycobacterium tuberculosis: Simple and inexpensive method for low-resource laboratories. Journal of Medical Microbiology, 55, 861–863.

    Article  CAS  PubMed  Google Scholar 

  47. Leung, K. L., Yip, C. W., Yeung, Y. L., et al. (2010). Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs. Journal of Applied Microbiology, 109, 2087–2094.

    Article  CAS  PubMed  Google Scholar 

  48. Lew, W., Pai, M., Oxlade, O., et al. (2008). Initial drug resistance and tuberculosis treatment outcomes: Systematic review and meta-analysis. Annals of Internal Medicine, 149, 123–134.

    Article  PubMed  Google Scholar 

  49. Machado, D., Couto, I., Perdigão, J., et al. (2013). Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis. PLoS One, 7, e34538.

    Article  CAS  Google Scholar 

  50. Mahajan, R. (2013). Bedaquiline: First FDA-approved tuberculosis drug in 40 years. International Journal of Applied & Basic Medical Research, 3(1).

    Google Scholar 

  51. Manissero, D., & Fernandez de la Hoz, K. (2006). Surveillance methods and case definition for extensively drug resistant TB (XDR-TB) and relevance to Europe: Summary update. Euro Surveillance, 11, e061103.

    PubMed  Google Scholar 

  52. Manjunatha, U. H., Boshoff, H., Dowd, C. S., et al. (2006). Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 103, 431–436.

    Article  CAS  PubMed  Google Scholar 

  53. Mathys, V., Wintjens, R., Lefevre, P., et al. (2009). Molecular genetics of Para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 53, 2100–2109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Matsumoto, M., Hashizume, H., Tomishige, T., et al. (2006). OPC-67683, a nitro-dihydroimidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS medic, 3, e466.

    Article  CAS  Google Scholar 

  55. Metcalfe, J. Z., Streicher, E., Theron, G., et al. (2017). Cryptic microheteroresistance explains Mycobacterium tuberculosis phenotypic resistance. American Journal of Respiratory and Critical Care Medicine, 196, 1191–1201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Middlebrook, G. (1954). Isoniazid-resistance and catalase activity of tubercle bacilli. Am Rev Tuberc, 69, 471–472.

    CAS  PubMed  Google Scholar 

  57. Miotto, P., Zhang, Y., Cirillo, D. M., & Yam, W. C. (2018). Drug resistance mechanisms and drug susceptibility testing for tuberculosis. Respirology, 23, 1098–1113.

    Article  PubMed  Google Scholar 

  58. Mitchison, D. A. (1985). The action of antituberculosis drugs in short-course chemotherapy. Tubercle, 66, 219–225.

    Article  CAS  PubMed  Google Scholar 

  59. Mondal, R., & Jain, A. (2007). Extensively drug-resistant Mycobacterium tuberculosis, India. Emerging Infectious Diseases, 13, 1429.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Musser, J. M. (1995). Antimicrobial agent resistance in mycobacteria: Molecular genetic insights. Clinical Microbiology Reviews, 8, 496–514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Muthaiah, M., Jagadeesan, S., Ayalusamy, N., et al. (2010). Molecular epidemiological study of pyrazinamide-resistance in clinical isolates of Mycobacterium tuberculosis from South India. International Journal of Molecular Sciences, 11, 2670–2680.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Pandey, B., Grover, S., Goyal, S., et al. (2018). Novel missense mutations in gidB gene associated with streptomycin resistance in Mycobacterium tuberculosis: Insights from molecular dynamics. Journal of Biomolecular Structure & Dynamics, 1–16.

    Google Scholar 

  63. Pasca, M. R., Guglierame, P., De Rossi, E., et al. (2005). mmpL7 gene of Mycobacterium tuberculosis is responsible for isoniazid efflux in Mycobacterium smegmatis. Antimicrobial Agents and Chemotherapy, 49, 4775–4777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Quan, S., Venter, H., & Dabbs, E. R. (1997). Ribosylative inactivation of rifampin by Mycobacterium smegmatis is a principal contributor to its low susceptibility to this antibiotic. Antimicrobial Agents and Chemotherapy, 41, 2456–2460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rad, M. E., Bifani, P., Martin, C., et al. (2003). Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerging Infectious Diseases, 9, 838.

    Article  CAS  PubMed Central  Google Scholar 

  66. Ramaswamy, S., & Musser, J. M. (1998). Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tubercle and Lung Disease, 79, 3–29.

    Article  CAS  PubMed  Google Scholar 

  67. Ramaswamy, S. V., Reich, R., Dou, S. J., et al. (2003). Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 47, 1241–1250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rattan, A., Kalia, A., & Ahmad, N. (1998). Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives. Emerging Infectious Diseases, 4, 195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rengarajan, J., Sassetti, C. M., Naroditskaya, V., et al. (2004). The folate pathway is a target for resistance to the drug para-aminosalicylic acid (PAS) in mycobacteria. Molecular Microbiology, 53, 275–282.

    Article  CAS  PubMed  Google Scholar 

  70. Safi, H., Lingaraju, S., Amin, A., et al. (2013). Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes. Nature Genetics, 45, 1190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sandgren, A., Strong, M., Muthu krishnan, P., et al. (2009). Tuberculosis drug resistance mutation database. PLoS Medicine, 6, e1000002.

    Article  CAS  PubMed Central  Google Scholar 

  72. Saunders, N. J., Trivedi, U. H., Thomson, M. L., et al. (2011). Deep resequencing of serial sputum isolates of Mycobacterium tuberculosis during therapeutic failure due to poor compliance reveals stepwise mutation of key resistance genes on an otherwise stable genetic background. The Journal of Infection, 62, 212–217.

    Article  PubMed  Google Scholar 

  73. Scorpio, A., Lindholm-Levy, P., Heifets, L., et al. (1997). Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 41, 540–543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Scorpio, A., & Zhang, Y. (1996). Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nature Medicine, 2, 662–667.

    Article  CAS  PubMed  Google Scholar 

  75. Sharma, A., Hill, A., Kurbatova, E., et al. (2017). Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: A mathematical modelling study. The Lancet Infectious Diseases, 17, 707–715.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Sharma, S. K., & Mohan, A. (2004). Multidrug-resistant tuberculosis. The Indian Journal of Medical Research, 120, 354–376.

    CAS  PubMed  Google Scholar 

  77. Siddiqi, N., Shamim, M., Hussain, S., et al. (2002). Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in North India. Antimicrobial Agents and Chemotherapy, 46, 443–450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Silva, M. S. N., Senna, S. G., Ribeiro, M. O., et al. (2003). Mutations in katG, inhA, and ahpC genes of Brazilian isoniazid-resistant isolates of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 41, 4471–4474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Siu, G. K. H., Zhang, Y., Lau, T. C., et al. (2011). Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. Antimicrob Chemother, 66, 730–733.

    Article  CAS  Google Scholar 

  80. Slayden, R. A., & Barry, C. E., III. (2000). The genetics and biochemistry of isoniazid resistance in Mycobacterium tuberculosis. Microbes and Infection, 2, 659–669.

    Article  CAS  PubMed  Google Scholar 

  81. Somoskovi, A., Parsons, L. M., & Salfinger, M. (2001). The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis. Respiratory Research, 2, 164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sreevatsan, S., Pan, X., Zhang, Y., et al. (1997). Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. Antimicrobial Agents and Chemotherapy, 41, 636–640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Stagg, H. R., Cohen, T., Becerra, M. C., et al. (2014). A tale of two settings: The role of the Beijing genotype in the epidemiology of multidrug-resistant tuberculosis. The European Respiratory Journal, 43, 632–635.

    Article  PubMed  Google Scholar 

  84. Sulochana, S., Narayanan, S., Paramasivan, C. N., et al. (2007). Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium tuberculosis from India. Journal of Chemotherapy, 19, 166–171.

    Article  CAS  PubMed  Google Scholar 

  85. Sun, Z., Zhang, J., Zhang, X., et al. (2008). Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates. International Journal of Antimicrobial Agents, 31, 115–121.

    Article  CAS  PubMed  Google Scholar 

  86. Suzuki, Y., Katsukawa, C., Tamaru, A. K. I., et al. (1998). Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene. Journal of Clinical Microbiology, 36, 1220–1225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Takayama, K., & Kilburn, J. O. (1989). Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrobial Agents and Chemotherapy, 33, 1493–1499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Takiff, H. E., Salazar, L., Guerrer, C., et al. (1994). Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrobial Agents and Chemotherapy, 38, 773–780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Taniguchi, H., Chang, B., Abe, C., et al. (1997). Molecular analysis of kanamycin and viomycin resistance in Mycobacterium smegmatis by use of the conjugation system. Journal of Bacteriology, 179, 4795–4801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Telenti, A., Imboden, P., Marchesi, F., et al. (1993). Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. The Lancet, 341, 647–651.

    Article  CAS  Google Scholar 

  91. Török, M. E., Reuter, S., Bryant, J., et al. (2013). Rapid whole-genome sequencing for investigation of a suspected tuberculosis outbreak. Journal of Clinical Microbiology, 51, 611–614.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Trauner, A., Liu, Q., Via, L. E. R., et al. (2017). The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy. Genome Biology, 18, 71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. van Rensburg, C. E., Joone, G. K., O'sullivan, J. F., et al. (1992). Antimicrobial activities of clofazimine and B669 are mediated by lysophospholipids. Antimicrobial Agents and Chemotherapy, 36, 2729–2735.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Vareldzis, B. P., Grosset, J., de Kantor, I., et al. (1994). Drug-resistant tuberculosis: Laboratory issues. World Health Organization recommendations. Tubercle and Lung Disease, 75, 1–7.

    Article  CAS  PubMed  Google Scholar 

  95. Victor, T. C., van Rie, A., Jordaan, A. M., et al. (2001). Sequence polymorphism in the rrs gene of Mycobacterium tuberculosis is deeply rooted within an evolutionary clade and is not associated with streptomycin resistance. Journal of Clinical Microbiolgy, 39, 4184–4186.

    Article  CAS  Google Scholar 

  96. Vilchèze, C., Av-Gay, Y., Attarian, R., et al. (2008). Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis. Molecular Microbiology, 69, 1316–1329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Vilcheze, C., Weisbrod, T. R., Chen, B., et al. (2005). Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrobial Agents and Chemotherapy, 49, 708–720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Willby, M., Sikes, R. D., Malik, S., et al. (2015). Correlation between GyrA substitutions and ofloxacin, levofloxacin, and moxifloxacin cross-resistance in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 59, 5427–5434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. World Health Organization. (2004). Global tuberculosis report. Geneva: WHO.

    Google Scholar 

  100. World Health Organization. (2012). Global tuberculosis report. Switzerland: WHO, Geneva.

    Google Scholar 

  101. World Health Organization. (2013). Global tuberculosis report. Switzerland: WHO, Geneva.

    Google Scholar 

  102. World Health Organization. (2013). Using the Xpert MTB/RIF assay to detect pulmonary and extrapulmonary tuberculosis and rifampicin resistance in adults and children: Expert group meeting report. http://who.int/tb/publications/xpert-mtb-rif-assay-diagnosis-meeting-report/eng/pdf

  103. World Health Organization. (2014). Global tuberculosis report. http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf

  104. World Health Organization. (2014). Xpert MTB/RIF implementation manual: Technical and operational ‘How-to’: Practical considerations. Geneva: WHO.

    Google Scholar 

  105. World Health Organization. (2017). Global tuberculosis report. Geneva: WHO.

    Google Scholar 

  106. Xavier, A. S., & Lakshmanan, M. (2014). Delamanid: A new armor in combating drug-resistant tuberculosis. Journal of Pharmacology and Pharmacotherapeutics, 5, 222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Xu, J., Wang, B., Hu, M., et al. (2017). Primary clofazimine and bedaquiline resistance among isolates from patients with multidrug-resistant tuberculosis. Antimicrobial Agents and Chemotherapy, 61, e00239–e00217.

    PubMed  PubMed Central  Google Scholar 

  108. Yadav, R. N., Singh, B. K., Sharma, S. K., et al. (2013). Comparative evaluation of GenoType MTBDRplus line probe assay with solid culture method in early diagnosis of multidrug resistant tuberculosis (MDR-TB) at a tertiary care Centre in India. PLoS One, 8, e72036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Yang, J. S., Kim, K. J., Choi, H., et al. (2018). Delamanid, bedaquiline, and linezolid minimum inhibitory concentration distributions and resistance-related gene mutations in multidrug-resistant and extensively drug-resistant tuberculosis in Korea. Annals of Laboratory Medicine, 38, 563–568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Yano, T., Kassovska-Bratinova, S., Teh, J. S., et al. (2011). Reduction of clofazimine by mycobacterial type 2 NADH: Quinone oxidoreductase a pathway for the generation of bactericidal levels of reactive oxygen species. The Journal of Biological Chemistry, 286, 10276–10287.

    Article  CAS  PubMed  Google Scholar 

  111. Zaunbrecher, M. A., Sikes, R. D., Metchock, B., et al. (2009). Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 106, 20004–20009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zaw, M. T., Emran, N. A., & Lin, Z. (2018). Mutations inside rifampicin-resistance determining region of rpoB gene associated with rifampicin-resistance in Mycobacterium tuberculosis. Journal of Infection and Public Health, 11, 605–610.

    Article  PubMed  Google Scholar 

  113. Zhang, M., Yue, J., Yang, Y. P., et al. (2005). Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China. Journal of Clinical Microbiology, 43, 5477–5482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Zhang, Y., & Young, D. B. (1993). Molecular mechanisms of isoniazid: A drug at the front line of tuberculosis control. Trends in Microbiology, 1, 109–113.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, India

    Chanchal Kumar, Kamal Shrivastava, Shraddha Gupta & Mandira Varma-Basil

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  1. Chanchal Kumar
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  2. Kamal Shrivastava
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  3. Shraddha Gupta
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  4. Mandira Varma-Basil
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Correspondence to Mandira Varma-Basil .

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  1. Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram, India

    Saif Hameed

  2. Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram, India

    Zeeshan Fatima

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Kumar, C., Shrivastava, K., Gupta, S., Varma-Basil, M. (2019). The Challenge of Drug-Resistant Tuberculosis: An Update. In: Hameed, S., Fatima, Z. (eds) Pathogenicity and Drug Resistance of Human Pathogens. Springer, Singapore. https://doi.org/10.1007/978-981-32-9449-3_2

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