Mycobacterium tuberculosis: Drug Resistance and Genetic Mechanisms - Facts, Artifacts, and Fallacies

AIDS and Tuberculosis: A Deadly Liaison

Volumn , Issue , 2009, Pages 103-121

  Böttger, Erik C ^a   Springer, Burkhard ^b  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Drug resistance; Epidemiology; Multidrug resistance; Resistance testing; Susceptibility; Tuberculosis

Indexed keywords

EID: 77955410915     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527627905.ch5     Document Type: Chapter

References (103)

1. Böttger, E.C. and Springer, B. (2008) Tuberculosis: drug resistance, fitness and strategies for global control. Eur. J. Pediatr., 167, 141-148.
2. Böttger, E.C. (2006) Mechanisms of mycobacterial drug resistance: implications for treatment and prevention strategies. Chemotherapy, 15, 23-28.
3. Whalen, C.C. (2006) Failure of directly observed treatment for tuberculosis in Africa: a call for new approaches. Clin. Infect. Dis., 42, 1048-1050.
4. van Helden, P.D., Donald, P.R., Victor, T.C., Schaaf, H.S., Hoal, E.G., Walzl, G. and Warren, R.M. (2006) Antimicrobial resistance in tuberculosis: an international perspective. Expert Rev. Anti.-Infect. Ther., 4, 759-766.
5. Schatz, A., Bugie, E. and Waksman, S.A. (1944) Substance exhibiting activity againstGram-positive andGram-negative bacteria. Proc. Soc. Exp. Biol. Med., 55, 66-69.
6. Lehman, J. (1946) Para-aminosalicylic acid in the treatment of tuberculosis. Lancet, 250, 15-16.
7. Pyle, M.M. (1947) Relative numbers of resistant tubercle bacilli in sputa of patients before and during treatment with streptomycin. Proc. Mayo Clin., 22, 465-473.
8. Medical Research Council (1949) Treatment of pulmonary tuberculosis with streptomycin and paraaminosalicylic acid. Br. Med. J., 2, 1521-1525.
9. Medical Research Council (1950) Treatment of pulmonary tuberculosis with streptomycin and para-amino salicylic acid. Br. Med. J., 2, 1073-1085.
10. British Thoracic Association (1982) A controlled trial of six month chemotherapy in pulmonary tuberculosis: second report results during the 24 months after the end of chemotherapy. Am. Rev. Respir. Dis., 126, 460-462.
11. Mitchinson, D.A. (1985) Mechanisms of the action of drugs in short-course chemotherapy. Bull. Int. Union Tuberc., 60, 36-40.
12. Fox, W., Ellard, G.A. and Mitchison, D.A. (1999) Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int. J. Tuberc. Lung Dis., 10 (Suppl. 2), S231-S279.
13. Connolly, L.E., Edelstein, P.H. and Ramakrishnan, L. (2007) Why is longterm therapy required to cure tuberculosis? PLOS Med., 4, e120.
14. WHO/IUATLO (2004) Global Project on Anti-Tuberculosis Drug Resistance Surveillance, Anti-tuberculosis drug resistance in the world: third global report. WHO/HTM/TB/2004.343. World Health Organization, Geneva.
15. van Rie, A., Warren, R., Richardson, M., Gie, R.P., Enarson, D.A., Beyers, N. and van Helden, P.D. (2000) Classification of drug-resistant tuberculosis in an epidemic area. Lancet, 356, 22-25.
16. Dye, C., Espinal, M.A.,Watt, C.J., Mbiaga, C. and William, B.G. (2002) Worldwide incidence of multidrug-resistant tuberculosis. J. Infect. Dis., 185, 1197-1202.
17. Dye, C., Scheele, S., Dolin, P., Pathania,V. and Raviglione, M.C. (1999) Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA, 282, 677-686.
18. Corbett, E.L., Watt, C.J., Walker, N., Maher, D., Williams, B.G., Raviglione, M.C. and Dye, C. (2003) The growing burden of tuberculosis: global trends and interactions with the HIVepidemic. Arch. Intern. Med., 163, 1009-1021.
19. Canetti, G. (1955) The tubercle bacillus in the pulmonary tuberculous lesion, in The TubercleBacillus (ed. G. Canetti), Springer Publishing Company, NY, pp. 29-85.
20. Ramaswamy, S. and Musser, J.M. (1998) Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber. Lung Dis., 79, 3-29.
21. Wade, M.M. and Zhang, Y. (2004) Mechanisms of drug resistance in Mycobacterium tuberculosis. Front. Biosci., 9, 975-994.
22. Finken, M., Kirschner, P., Meier, A., Wrede, A. and Böttger, E.C. (1993) Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alteration of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. Mol. Microbiol., 9, 1239-1246.
23. Blower, S.M. and Chou, T. (2004) Modeling the emergence of the "hot zones": tuberculosis and the amplification dynamics of drug resistance. Nat. Med., 10, 1111-1116.
24. van Solingen, D., Borgdorff, M.W., de Haas, P.E., Sebek, M.M., Veen, J., Dessens, M., Kremer, K. and van Embden, J.D. (1999) Molecular epidemiology of tuberculosis in the Netherlands: a nationwide study from 1993 through 1997. J. Infect. Dis., 180, 726-736.
25. van Solingen, D., de Haas, P.E., van Doorn, H.R., Kuijper, E., Rinder, H. and Borgdorff, M.W. (2000) Mutations at amino acid position 315 of the katG gene are associated with high-level resistance to isoniazid, other drug resistance, and successful transmission of Mycobacterium tuberculosis in the Netherlands. J. Infect. Dis., 182, 1788-1790.
26. Marttila, H.J., Soini, H., Eerola, E., Vyshnevskya, E., Vyshnevskaya, B.I., Otten, T.F., Vasilyef, A.V. and Viljanen, M.K. (1998) A Ser315Thr substitution in KatG is predominant in genetically heterogeneous multidrug-resistant Mycobacterium tuberculosis isolates originating from the St. Petersburg area in Russia. Antimicrob. Agents Chemother., 42, 2443-2445.
27. Sherman, D.R., Mdluli, K., Hickey, M.J., Arain, T.M., Morris, S.L., Barry, C.E. 3rd, and Stover, C.K. (1996) Compensatory ahpC gene expression in isoniazidresistant Mycobacterium tuberculosis. Science, 272, 1641-1643.
28. Pfister, P., Corti, N., Hobbie, S.N., Bruell, C., Zarivach, R., Yonath, A. and Böttger, E.C. (2005) 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A ! G. Proc. Natl Acad. Sci. USA, 102, 5180-5185.
29. Afanas'ev, M.V., Ikryannikova, L.N., Il'ina, E.N., Sidorenko, S.V., Kuz'min, A.V., Larionova, E.E., Smirnova, T.G. et al. (2007) Molecular characteristics of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis isolates from the Russian Federation. J. Antimicrob. Chemother., 59, 1057-1064.
30. Meier, A., Kirschner, P., Bange, F.C., Vogel, U. and Böttger, E.C. (1994)Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance. Antimicrob. Agents Chemother., 38, 228-233.
31. Andersson, D.I. and Levin, B.R. (1999) The biological cost of antibiotic resistance. Curr. Opin. Microbiol., 2, 489-493.
32. Bjorkman, J., Nagaev, I., Berg, O.G., Hughes, D. and Andersson, D.I. (2000) Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science, 287, 1479-1482.
33. Böttger, E.C., Springer, B., Pletschette,M. and Sander, P. (1998) Fitness cost of antibiotic-resistant microorganisms and compensatory mutations. Nat. Med., 4, 1343-1344.
34. Sander, P., Springer, B., Prammananan, T., Sturmfels, A., Kappler, M., Pletschette, M. and Böttger, E. C. (2002) Fitness cost of chromosomal drug resistance-conferring mutations. Antimicrob. Agents Chemother., 46, 1204-1211.
35. Böttger, E.C., Pletschette, M. and Andersson,D. (2005) Drug resistance and fitness cost in Mycobacterium tuberculosis infection. J. Infect. Dis., 191, 823-824.
36. Canetti, G., Froman, S., Grosset, J., Hauduroy, P., Langerová, M., Mahler, H.T., Meissner, G. et al. (1963) Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull. World Health Org., 29, 565-578.
37. Inderlied, C.B. and Salfinger, M. (1995) Antimicrobial agents and susceptibility tests: mycobacteria, in Manual of Clinical Microbiology (eds P.R. Murray, E.J. Baron, M.A. Pfaller, F.C. Tenover and R.H. Yolken), American Society for Microbiology, Washington, DC, pp. 1385-1404.
38. Parsons, L.M., Somoskövi, A., Urbanczik, R. and Salfinger, M. (2004) Laboratory diagnostic aspects of drug resistant tuberculosis. Front. Biosci., 9, 2086-2105.
39. Canetti, G., Fox, W., Khomenko, A., Mahler, H.T., Menon, N.K., Mitchison, D.A., Rist, N. and Smelev, N.A. (1969) Advances in techniques of testing mycobacterial drug sensitivity and the use of sensitivity tests in tuberculosis control programmes. Bull. World Health Org., 41, 21-43.
40. Siddiqi, S.H.,Hawkins, J.E. and Laszlo, A. (1985) Interlaboratory drug susceptibility testing of Mycobacterium tuberculosis by a radiometric procedure and two conventional methods. J. Clin. Microbiol., 22, 919-923.
41. Woodley, C.L. (1986) Evaluation of streptomycin and ethambutol concentrations for susceptibility testing of Mycobacterium tuberculosis by radiometric and conventional procedures. J. Clin. Microbiol., 23, 385-386.
42. Lee, C.N. and Heifets, L.B. (1987) Determination of minimal inhibitory concentrations of antituberculosis drugs by radiometric and conventional methods. Am. Rev. Respir. Dis., 136, 349-352.
43. Madison, B., Robinson-Dunn, B.,George, I., Gross, W., Lipman, H., Metchock, B., Sloutsky, A. et al. (2002) Multicenter evaluation of ethambutol susceptibility testing of Mycobacterium tuberculosis by agar proportion and radiometric methods. J. Clin. Microbiol., 40, 3976-3979.
44. Laszló, A., Rahman, M., Raviglione, M. and Bustreo, F. (1997) WHO/IUATLD Network of Supranational Reference Laboratories, Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD supranational laboratory network: first round of proficiency testing. Int. J. Tuberc. Lung Dis., 1, 231-238.
45. Laszló, A., Rahman, M., Espinal, M. and Raviglione, M. (2002) WHO/IUATLD Network of Supranational Reference Laboratories, Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD supranational laboratory network: five rounds of proficiency testing, 1994-1998. Int. J. Tuberc. Lung Dis., 6, 748-756.
46. Zhang, Y. and Mitchison, D. (2003) The curious characteristics of pyrazinamide: a review. Int. J. Tuberc. Lung Dis., 7, 6-21.
47. Konno, F., Feldmann, F.M. and McDermott, W. (1967) Pyrazinamide susceptibility and amidase activity of tubercle bacilli. Am. Rev. Respir. Dis., 95, 461-469.
48. Brander, E. (1972) A simple way of detecting pyrazinamide resistance. Tubercle, 53, 128-130.
49. Wayne, L.G. (1974) Simple pyrazinamidase and urease tests for routine identification of mycobacteria. Am. Rev. Respir. Dis., 109, 147-151.
50. Miller, M.A., Thibert, L., Desjardins, F., Siddiqi, S.H. and Dascal, A. (1995) Testing of susceptibility of Mycobacterium tuberculosis to pyrazinamide: comparison of BACTEC method with pyrazinamidase assay. J. Clin. Microbiol., 33, 2468-2470.
51. Espinal, M.A., Kim, S.I., Suarez, P.G., Kam, K.M., Khomenko, A.G., Migliori, G.B., Baez, J. et al. (2000) Standard shortcourse chemotherapy for drug-resistant tuberculosis: treatment outcome in 6 countries. JAMA, 283, 2537-2545.
52. DeRiemer, K., Garcia-Garcia, L., Bobadilla-del-Valle, M., Palacios- Martinez, M., Martinez-Gamboa, A., Small, P.M., Sifuentes-Osornio, J. and Ponce-de-Léon, A. (2005) Does DOTS work in populations with drug-resistant tuberculosis? Lancet, 365, 1239-1245.
53. Meier, A., Sander, P., Schaper, K.J., Scholz, M. and Böttger, E.C. (1996) Correlation of molecular resistance mechanism and phenotypic resistance level in streptomycin-resistant M. tuberculosis. Antimicrob. Agents Chemother., 40, 2452-2454.
54. Victor, T.C., Warren, R., Butt, J.L., Jordaan, A.M., Felix, J.V., Venter, A., Sirgel, F.A. et al. (1997)Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis. J. Med. Microbiol., 46, 847-857.
55. Stewart, S.M. and Crofton, J.W. (1964) The clinical significance of low degrees of drug resistance in pulmonary tuberculosis. Am. Rev. Respir. Dis., 89, 811-829.
56. Moulding, T.S. (1981) Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance? Am. Rev. Respir. Dis., 123, 262-264.
57. Cynamon, M.H., Zhang, Y., Harpster, T., Cheng, S. and DeStefano, M.S. (1999) High-dose isoniazid therapy for isoniazid-resistant murine Mycobacterium tuberculosis infection. Antimicrob. Agents Chemother., 43, 2922-2924.
58. Tripathy, S.P., Menon, N.K., Mitchison, D.A., Narayana, A.S., Somasundaram, P.A., Stott, H. and Velu, S. (1969) Response to treatment with isoniazid plus PAS of tuberculous patients with primary isoniazid resistance. Tubercle, 50, 257-268.
59. Devadatta, S., Bhatia, A.L., Andrews, R.H., Fox, W., Mitchison, D.A., Radhakrishna, S., Ramakrishnan, C.V. et al. (1961) Response of patients infected with isoniazid-resistant tubercle bacilli to treatment with isoniazid plus PAS or isoniazid alone. Bull. World Health Org., 25, 807-829.
60. Petty, T.L. and Mitchell, R.S. (1962) Successful treatment of advanced isoniazid- and streptomycin-resistant pulmonary tuberculosis with ethionamide, pyrazinamide, and isoniazid. Am. Rev. Respir. Dis., 86, 503-512.
61. Böttger, E.C. (2001) Drug resistant tuberculosis. Lancet, 357, 1288-1289.
62. NCCLS (2003) Susceptibility Testing of Mycobacteria, Nocardiae, and other Aerobic Actinomycetes, NCCLS document M24-A, NCCLS, Wayne, Pennsylvania, USA, 1- 56238-500-3.
63. Huitric, E., Werngren, J., Juréen, P. and Hoffner, S. (2006) Resistance levels and rpoB gene mutations among in vitroselected rifampicin-resistant Mycobacterium tuberculosis mutants. Antimicrob. Agents Chemother., 50, 2860-2862.
64. Morlock, G.P., Metchock, B., Sikes, D., Crawford, J.T. and Cooksey, R.C. (2003) ethA, inhA, and katG loci of ethionamideresistant clinical Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother., 47, 3799-3805.
65. Springer, B., Calligaris-Maibach, R.C., Ritter, C. and Böttger, E.C. (2008) Tuberculosis drug resistance in an area of low endemicity in 2004 to 2006: semiquantitative drug susceptibility testing and genotyping. J. Clin. Microbiol., 46, 4064-4067.
66. Banerjee, A., Dubnau, E., Quemard, A., Balasubramanian, V., Um, S.K., Wilson, T., Collins, D. et al. (1994) inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science, 263, 227-230.
67. Somoskovi, A., Dormandy, J., Mitsani, D., Rivenburg, J. and Salfinger,M. (2006) Use of smear-positive samples to assess the PCR-based genotype MTBDR assay for rapid, direct detection of the Mycobacterium tuberculosis complex as well as its resistance to isoniazid and rifampicin. J. Clin. Microbiol., 44, 4459-4463.
68. Cox, H.S., Niemann, S., Ismailov, G., Doshetov, D., Orozco, J.D., Blok, L., Rüsch-Gerdes, S. and Kebede, Y. (2007) Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance. Clin. Infect. Dis., 44, 1421-1427.
69. Stover, C.K., Warrener, P., Van Devanter, D.R., Sherman, D.R., Arain, T.M., Langhorne, M.H., Anderson, S.W. et al. (2000) A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature, 405, 962-966.
70. Nuermberger, E., Rosenthal, I., Tyagi, S., Williams, K.N., Almeida, D., Peloquin, C.A., Bishai, W.R. and Grosset, J.H. (2006) Combination chemotherapy with the nitroimidazopyran PA-824 and firstline drugs in a murine model of tuberculosis. Antimicrob. Agents Chemother., 50, 2621-2625.
71. Andries, K., Verhasselt, P.,Guillemont, J., Göhlmann, H.W., Neefs, J.M., Winkler, H., Van Gestel, J. et al. (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science, 307, 223-227.
72. Lounis, N., Veziris, N., Chauffour, A., Truffot-Pernot, C., Andries, K. and Jarlier, V. (2006) Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis have the potential to shorten treatment duration. Antimicrob. Agents Chemother., 50, 3543-3547.
73. Ibrahim, M., Andries, K., Lounis, N., Chauffour, A., Truffot-Pernot, C., Jarlier, V. and Veziris, N. (2007) Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. Antimicrob. Agents Chemother., 51, 1011-1015.
74. Springer, B., Lucke, K., Calligaris- Maibach, R., Ritter, C. and Böttger, E.C. (2009) Quantitative drug susceptibility testing of Mycobacterium tuberculosis by use of MGIT960 and Epicenter Instrumentation, J. Clin. Microbiol., 47, 1773-1780.
75. Zhang, Y., Heym, B., Allen, B., Young, D. and Cole, S. (1992) The catalaseperoxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature, 358, 591-593.
76. Rouse, D.A., Li, Z., Bai, G.H. and Morris, S.L. (1995) Characterization of the katG and inhA genes of isoniazid resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 39, 2472-2477.
77. Musser, J.M., Kapur, V., Williams, D.L., Kreiswirth, B.N., van Soolingen, D. and van Embden, J.D. (1996) Characterization of the catalase-peroxidase gene (katG) and inhA locus in isoniazid-resistant and - susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing: restricted array of mutations associated with drug resistance. J. Infect. Dis., 173, 196-202.
78. Dobner, P., Rusch-Gerdes, S., Bretzel, G., Feldmann, K., Rifai, M., Loscher, T. and Rinder, H. (1997) Usefulness of Mycobacterium tuberculosis genomic mutations in the genes katG and inhA for the prediction of isoniazid resistance. Int. J. Tuberc. Lung Dis., 1, 365-369.
79. Telenti, A., Imboden, P., Marchesi, F., Lowrie, D., Cole, S.T., Colston, M.J., Matter, L. et al. (1993) Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet, 341, 647-650.
80. Williams, D., Spring, L., Collins, L., Miller, L.P., Heifets, L., Gangadharam, P.R. and Gillis, T.P. (1998) Contribution of rpoB mutation to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 42, 1853-1857.
81. Scorpio, A. and Zhang, Y. (1996) Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat. Med., 2, 662-667.
82. Scorpio, A., Lindholm-Levy, P., Heifets, L., Gilman, R., Siddiqi, S., Cynamon, M. and Zhang, Y. (1997) Characterization of pncA mutations in pyrazinamideresistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 41, 540-543.
83. Mestdagh, M., Fonteyne, P.A., Realini, L., Rossau, R., Jannes, G., Mijs,W., De Smet, K.A. et al. (1999) Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 43, 2317-2319.
84. Lemaitre, N., Sougakoff, W., Truffot-Pernot, C. and Jarlier, V. (1999) Characterization of new mutations in pyrazinamide resistant strains of Mycobacterium tuberculosis and identification of conserved regions important for the catalytic activity of the pyrazinamidase pncA. Antimicrob. Agents Chemother., 43, 1761-1763.
85. Morlock, G.P., Crawford, J.T., Butler, W.R., Brim, S.E., Sikes, D., Mazurek, G.H., Woodley, C.L. and Cooksey, R.C. (2000) Phenotypic characterization of pncA mutants of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 44, 2291-2295.
86. Belanger, A.E., Besra, G.S., Ford, M.E., Mikosova, K., Belsle, J.R., Brennan, P.J. and Inamine, J.M. (1996) The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl Acad. Sci. USA, 93, 11919-11924.
87. Telenti, A., Philipp, W.J., Screevatsan, S., Bernasconi, C., Stockbauer, K.E., Wieles, B.,Musser, J.M. and Jacobs,W.R. Jr (1997) The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat. Med., 3, 567-570.
88. Madison, B., Robinson-Dunn, B.,George, I., Gross, W., Lipman, H., Metchuck, B., Sloctsky, A. et al. (2002) Multicenter evaluation of ethambutol susceptibility testing of Mycobacterium tuberculosis by agar proportion and radiometric methods. J. Clin. Microbiol., 40, 3976-3979.
89. Plinke, C., Rüsch-Gerdes, S. and Niemann, S. (2006) Significance of mutations in embB codon 306 for prediction of ethambutol resistance in clinical Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother., 50, 1900-1902.
90. Johnson, R., Jordaan, A.M., Pretorius, L., Engelke, E., van der Spuy, G., Kewley, C., Bosman, M. et al. (2006) Ethambutol resistance testing by mutation detection. Int. J. Tuberc. Lung Dis., 10, 68-73.
91. Safi, H., Sayers, B., Hazbón, M.H. and Alland, D. (2008) Transfer of embB codon 306 mutations into clinical Mycobacterium tuberculosis strains alters susceptibility to ethambutol, isoniazid and rifampin. Antimicrob. Agents Chemother., 52, 2027-2034.
92. Honore, N. and Cole, S.T. (1994) Streptomycin resistance in mycobacteria. Antimicrob. Agents Chemother., 38, 238-242.
93. Sreevatsan, S., Pan, X., Stockbauer, K., Williams, D., Kreiswirth, B. and Musser, J.M. (1996) Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographical localities. Antimicrob. Agents Chemother., 40, 1024-1026.
94. Cooksey, R. C., Morlock, G. P., Mcqueen, A., Glickman, S. E., Crawford, J. T. (1996) Characterization of streptomycin resistance mechanisms among Mycobacterium tuberculosis isolates from New York City. Antimicrob. Agents Chemother, 40, 1186-1188.
95. Okamoto, S., Tamaru, A., Nakajima, C., Nishimura, K., Tanaka, Y., Tokuyama, S., Suzuki, Y. and Ochi, K. (2007) Loss of a conserved 7-methylguanosine modification in 16S rRNA confers lowlevel streptomycin resistance in bacteria. Mol. Microbiol., 63, 1096-1106.
96. Sander, P., Prammananan, T. and Böttger, E.C. (1996) Introducing mutations into a chromosomal rRNA gene using a genetically modified eubacterial host with a single rRNA operon. Mol. Microbiol., 22, 841-848.
97. Suzuki, Y., Katsukava, C., Tamaru, A., Abe, C., Makino, M., Mizuguchi, Y. and Taniguchi, H. (1998) Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene. J. Clin. Microbiol., 36, 1220-1225.
98. Alangaden, G.J., Kreiswirth, B., Aouad, A., Khetarpal, M., Igno, F.R., Moghazeh, S.L., Manavathu, E.K. and Lerner, S.A. (1998) Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 42, 1295-1297.
99. Hobbie, S.N., Bruell, C., Kalapala, S., Akshay, S., Schmidt, S., Pfister, P. and Böttger, E.C. (2006) A genetic model to investigate drug-target interactions at the ribosomal decoding site. Biochimie, 88, 1033-1043.
100. Takiff, H.E., Salazar, L., Guerrero, C., Philipp, W., Huang, W.M., Kreiswirth, B., Cole, S.T. et al. (1994) Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob. Agents Chemother., 38, 773-780.
101. Chan, R.C.,Hui, M., Chan, E.W., Au, T.K., Chin, M.L., Yip, C.K., AuYeang, C.K. et al. (2007) Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. J. Antimicrob. Chemother., 59, 866-873.
102. DeBarber, A.E., Mdluli, K., Bosman, M., Bekker, L.G. and Barry, C.E. 3rd (2000) Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA, 97, 9677-9682.
103. Wang, F., Langley, R., Gulten, G., Dover, L.G., Besra, G.S., Jacobs, W.R. Jr, and Sacchettini, J.C. (2007) Mechanism of thioamide drug action against tuberculosis and leprosy. J. Exp. Med., 204, 73-78.