Molecular Approaches in Mycobacterium tuberculosisand Other Infections Caused by Mycobacterium Species

  • Madhu Goyal
  • Douglas Young
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 15)


The genus Mycobacterium consists of a diverse group of organisms that are ubiquitous and are believed to be some of the oldest bacteria on earth. They may exist as free-living commensals inhabiting soil and water, but they are also potentially pathogenic to man and other animals, being transmitted by airborne or droplet spread. At least 25 species of mycobacteria have been associated with human disease. Robert Koch in 1882, identified the acid-fast bacterium (AFB), Mycobacterium tuberculosis as the causative agent of tuberculosis (TB). TB is an ancient disease that remains a significant global health problem With improved living standards and the introduction of chemotherapy in 195Os, the incidence of TB in most industrialized countries showed a progressive decline, with very little mortality by the mid 1980s. This pattern has changed over the last decade


Human Immunodeficiency Virus High Performance Liquid Chromatography Polymerase Chain Reaction Assay Tuberculin Skin Test rpoB Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Dolm, P.J., Ravighone, M C., and Kochi, A. (1994) Global tuberculosis incidence and mortality during 1990–2000. Bull World Health Organ 72, 213–220Google Scholar
  2. 2.
    Barnes, P.F., Bloch, A B., Davidson, P.T., and Snider, D. E., Jr (1991) Tuberculosis in patients with human immunodeticiency virus infection N Engl J Med 324, 1644–1650PubMedCrossRefGoogle Scholar
  3. 3.
    Harries, A. D.(1990) Tuberculosis and human immunodeficiency virus infection in developing countries. Lancet 335, 387–390.PubMedCrossRefGoogle Scholar
  4. 4.
    Huebner, R. E, Schem, M. F., and Bass, J. B., Jr. (1993) The tuberculin skin test. Clin Infect Dis 17, 968–975PubMedGoogle Scholar
  5. 5.
    Horsburgh, D R (1991) Mycobacterium avium complex infection in the acquired immunodeficiency syndrome N Engl J Med. 324, 1332–1338.PubMedCrossRefGoogle Scholar
  6. 6.
    Middlebrook, G., Reggiardo, Z., and Tigertt, W D (1977) Automatable radio-metric detection of growth of Mycobacterium tuberculosis in selective media Am. Rev Respir Dis 115, 1066–1069.PubMedGoogle Scholar
  7. 7.
    Palact, M, Ueki, Y M, Soto D N, Telles, M A, da Silva, Curcio, M, and Silva, E A. M (1996) Evaluation of Mycobacteria growth indicator tube for recovery and drug susceptibility testing of Mycobacterium tuberculosis isolates from respiratory specimens J Clin Microbiol 34, 762–764Google Scholar
  8. 8.
    Hanna, B A., Walters, S B., Kodsi, S E., Stitt, D.T, Tierno, P.M, and Tick, L J. (1994) Detection of Mycobacterium tuberculosis directly from patients specimens with the Mycobacteira Growth indicator tube a new rapid method in “Program and abstracts of the 94th General Meeting of the American Society for Microbiology” (abst. C-112) American Society for Microbiology, D C., p 510Google Scholar
  9. 9.
    Butler, W R, and Kilburn, J.O (1988) Identification of major slowly growing pathogenic mycobacteria and Mycobacterium gordonae by high performance liquid chromatography of their mycolic acids. J Clin Mycrobiol 26, 50–53Google Scholar
  10. 10.
    Jost, K.C, Jr, Dunbar, D F, Barth, S.S, Headley, V L., and Elliott, L.B (1995) Identification of Mycobacterium tuberculosis and M avium complex directly from smear positive sputum specimens and BACTEC 12B cultures by high performance liquid chromatography with fluorescence detection and computer driven recognition models J Clin. Microbiol 33, 1270–1277PubMedGoogle Scholar
  11. 11.
    French, G L, Chan, C.Y, Poon, D., Cheung, S.W., and Cheng, A.F. (1990) Rapid diagnosis of bacterial meningitis by the detection of a fatty acid marker in CSF with gas chromatography mass spectrometry and selected ion monitoring J Med Microbiol 31, 21–26PubMedCrossRefGoogle Scholar
  12. 12.
    Butler, W R, Jost, K C., Jr, and Kilburn, J.0 (1991) Identification of mycobacteria by high performance liquid chromatography J Clin Micrbiol 29, 2468–2472Google Scholar
  13. 13.
    French, G L, Teoh, R, Chan, C Y, Humphries, M. J., Cheung, S.W., and O’Mahony, G. (1987) Diagnoses of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid. Lancet 2, 117–119.PubMedCrossRefGoogle Scholar
  14. 14.
    Larsson, L., Mardh, P A., Odham, G., and Westerdahl, G (1980) Detection of tuberculostearic acid in biological specimens by means of glass capillary gas-chromatography electron and chemical ionzation mass spectrometry, utilizing selected ion monitoring. J Chromaogr 163, 22l–224Google Scholar
  15. 15.
    Drake, T. A., Hindler, J. A., Berlin, O.G W, and Bruckner, D A (1987) Rapid identification of Mycobacterium avium complex in culture using DNA probes. J Clin Mirobiol 25, 1442–1445Google Scholar
  16. 16.
    Lim, S D, Todd, J, Lopez, J, Ford, E, and Janda, M (1991) Genotypic identification of pathogenic Mycobacterium species by using a non radioactive oligonucleotide probe. J. Clin Microbiol.29, 1276–1278.PubMedGoogle Scholar
  17. 17.
    Goto, M, Oka, S, Okuzumi, K., Kimura S., and Shimada, K. (1991) Evaluation of acridimum ester labelled DNA probes for identification of Mycobacterium iuberculosis and Mycobacterium intracellulare complex in culture J Clin Microbiol 29, 2473–2PubMedGoogle Scholar
  18. 18.
    Evans, K. D., Nakasone, A S., Sutherland, P. A, de la Maza, L M., and Peterson, E. M. (1992) Identification of Mycobacterium tuberculosis and Mycobacterium avium-M intracellulare directly from primary BACTEC cultures by using acridmmm ester labeled DNA probes, J Clin. Microbiol 30, 2427–2431PubMedGoogle Scholar
  19. 19.
    Ureda, M S (1991) Controlled synthetic oligonucleotide networks for the detection of pathogenic organisms, in Rapid methods and automation in microbiology and immunology (Vaheri, A, Tilton, R C., and Balows, A, eds.), Springer-Verlag, Berlin, pp. 1–5Google Scholar
  20. 20.
    Liu, J., Robinson, L., Buxton, D, et al (1994) The use of Q beta signal amplification technology for the rapid detection of Mycobacterium tuberculosis complex directly from smear negative sputum specimens in Abstracts of the 94th general meeting of the American Society for Microbiologists (Las Vegas), (abst U-98) American Society for Microbiology, Washington, DC.Google Scholar
  21. 21.
    An, Q., Buxton, D., Hendricks, A, Robinson, L., Shah, J, Lu, L, Vera Gracra, M, King, W, and Olive, D M (1995) Comparison of amplified Q beta rephcase and PCR assays for detection of Mycobacterium tuberculosis J Clin Microbiol 33, 860–867.PubMedGoogle Scholar
  22. 22.
    Eisenach, K D, Cave, M D, Bates, J H, and Crawford, J. T(1990) Polymerase chain amplification of a repetitive DNA sequence for Mycobacterium tuberculosis J Inf Dis 161, 977–981.Google Scholar
  23. 23.
    Walker, G T, Nadeau, J G., Spears, P.A., Schram, J.L, Nycz, C M., and Shank, D D (1994) Multiplex strand displacement amplification (SDA) and detection of DNA sequences from Mycobacterium tuberculosis and other mycobacteria Nucleic Acids Res.22, 2670–2677PubMedCrossRefGoogle Scholar
  24. 24.
    Leckie, G, Cao, J, Davis, A., Facey, I, Lin, B.C., and Lee, H (1994) Ligasechain reaction (LCR) DNA amplification for direct detection of Mycobacterium tuberculosis in clinical specimens in Abstracts of the 94th general meeting of the American Society for Microbiologisis (Las Vegas) (abst U-96) American society for Microbiology, Washington, DCGoogle Scholar
  25. 25.
    Anderson, A B., Thybo, S., Godfrey-Faussett, P., and Stoker, N. G. (1993) Polymerase chain reaction for detection of Mycobacterium tuberculosis sputum Eur J Clin Microbiol Infect Dis 12, 922–927CrossRefGoogle Scholar
  26. 26.
    Hermans, P W M., Schurtema, A. R J., van Sooloigen, D., Verstynen, C P H J., Bik, E. M., Thole, J E R, Kolk, A H. J., and van Embden, J.D.A. (1990) Specific detection of Mycobacterium tuberculosis complex strains by polymerase chain reaction J Clin Microbiol. 28, 1204–1213PubMedGoogle Scholar
  27. 27.
    Boddinghaus, B, Rogall, T, Flohr, T., Blocker, H., and Bottger, E. C. (1990) Detection and identification of mycobacteria by amplification of rRNA J Clin Microbiol 28, 1751–1759PubMedGoogle Scholar
  28. 28.
    Brisson-Noel, A., Gicquel, B., Lecossier, D., Levy-Frebault, V., Nassif, X., and Hance, A. J. (1989) Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in clinical samples. Lancet 2, 1069–1071.PubMedCrossRefGoogle Scholar
  29. 29.
    Sjobring, U, Meclenburg, M., Anderson, A B., and Miorner, H (1990) Polymerase chain reaction for the detection of Mycobacterium tuberculosis J Clin Microbiol 28, 2200–2204PubMedGoogle Scholar
  30. 30.
    Kaneko, K, Onodera, O, Miyatake, T, and Tsuji, S (1990) Rapid diagnoses of tuberculous meningitis by polymerase chain reaction (PCR) Neurology 40, 1617–1618PubMedGoogle Scholar
  31. 31.
    Cousins, D.V, Wilton, S D., Francis, B. R., and Gow, B. L. (1992) Use of polymerase chain reaction for rapid diagnosis of tuberculosis.J Clin Microbiol 30, 255–258PubMedGoogle Scholar
  32. 32.
    Hermans, P W M, van Soolingen, D., Dale, J W., Schuitema, A R J, McAdam, R. A, Catty, D., and van Embden, J. D A (1990) Insertion element IS986 from Mycobacterium tuberculosis: a useful tool for diagnosis and epidemiology of tuberculosis J Clin Microbiol 28, 2051–2058PubMedGoogle Scholar
  33. 33.
    De Wit, O., Steyn, L, Shoemaker, S., and Sogin, M. (1990) Direct detection of Mycobacterium tuberculosis in clnical specimens by DNA amplification.J Clin Microbiol 28, 2431–2441Google Scholar
  34. 34.
    Ralphs, N T., Garrett, S., Morse, R., Cookson, J.B., Andrew, P.W, and Boulnois, G J. (1991) A DNA primer probe system for the rapid and sensitive detection of Mycobacterium tuberculosis complex pathogens J Appl Bacteriol 70, 22l–226Google Scholar
  35. 35.
    De Wit, D, Wootton, M, Allan, B., and Steyn, L. (1993) Simple method for production of internal control DNA for Mycobacterium tuberculosis polymerase chain reaction.Am. Rev Respir Dis 144, 1160–1163.Google Scholar
  36. 36.
    Hermans, P. W. M, van Soolingen, D., Bik, E M, de Haas, P E W., Dale, J W,and van Embden, J.D A (1991) The insertion element IS987 from Mycobacterium bows BCG is located in a hot-spot integration region for insertion elements in Mycobacterium complex strains. Infect.Immun 59, 2695–2705.PubMedGoogle Scholar
  37. 37.
    Thierry, D, Cave, M. D, Eisenach, K. D, Crawford, J T., Bates, J H., Gicquel, B, and Guesdon, J L. (1990) IS6110, an IS-like element of Mycobacterium tuberculosis complex.Nucleic Acids Res 18, 188.PubMedCrossRefGoogle Scholar
  38. 38.
    Kolk, A. H J, Schuitema, A. R J., Kuijper, S, van Leeuwen, J, Hermans, P. W M., van Embden, J D.A., and Hartskeel, R.A. (1992) Detectton of Mycobacterium tuberculosis in clinical samples by using polymerase chain reaction and a nonradioactive detection system.J Clin Microbiol 30, 2567–2575.PubMedGoogle Scholar
  39. 39.
    Eisenach, K. D, Sifford, M D., Cave, M. D, Bates, J. H, and Crawford, J T (1991) Detection of Mycobacterium tuberculosis in sputum samples using a polymerase chain reaction Am Rev Respir Dis 144, 1160–1163PubMedGoogle Scholar
  40. 40.
    Nolte, F S., Metchock, B., McGowen, J. E., Jr., Edwards, A., Okwumabna, 0, Thurmond, C, Mitchell, P. S, Plikaytis, B, and Shinnick, T (1993) Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridization. J Clin Microbiol 31, 1777–1782.PubMedGoogle Scholar
  41. 41.
    Shawar, R. M., El-Zaatari, F. A. K., Nataraj, A., and Clarridge, J E. (1993) Detection of Mycobacterium tuberculosis in clinical samples by two step polymerase chain reaction and nonisotopic hybridization methods.J. Clin Microbiol 31, 6l–65Google Scholar
  42. 42.
    Clarridge, J. E R., Shawar, R. M., Shinnick, T M., and Plikaytis, B B. (1993) Large scale use of polymerase chain reaction for detection of Mycobacterium tuberculosis in a routine mycobacterilogy laboratory J Clin Microbiol 31, 2049–2056.PubMedGoogle Scholar
  43. 43.
    Walker, D A, Taylor, I K., Mitchell, D. M, and Shaw, R. (1992) Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis Thorax 47, 690–694.PubMedCrossRefGoogle Scholar
  44. 44.
    Yuen, L K, Ross, B C., Jackson, K M, and Dwyer, B. (1993) Characterization of Mycobacterium tuberculosis strains from Vietnamese patients by Southern blot hybridization. J Clin Microbiol 31, 1615–1618PubMedGoogle Scholar
  45. 45.
    Schulger, N. W., Kinney, D., Harkin T J., and Rom, W. N (1994) Clinical utility of the polymerase chain reaction in the diagnosis of infections due to Mycobacterium tuberculosis. Chest 105, 1116–1121CrossRefGoogle Scholar
  46. 46.
    Beige, J., Lokles, J., Schaberg, T., Finckh, U, Fischer, M., Mauch, H., Lode, H, Kohler, B., and Rolfs, A (1995) Clinical evaluation of Mycobucterium tuberculosis assay.J Clin Microbiol 33, 90–95PubMedGoogle Scholar
  47. 47.
    Noordhoek, G T, Kolk, A H J, Bjune, G., Catty, D, Dale, J. W, Fine, P E., Godfrey Fausset, P, Cho, S N., Shinnick, T, and Sevenson, S V. (1994) Sensitivity and specificity of PCR for detection of Mycobacterium tuberculosis a blind comparison study among seven laboratories J Clin Microbiol.32, 277–284.PubMedGoogle Scholar
  48. 48.
    Savic, B., SJobring, U., Alugupalli, S., Larrson, L., and Miorner, H (1992) Evaluation of polymerase chain reaction, tuberculostearic acid analysis, and direct microscopy for the detection of Mycobacteriu in sputum. J. Inf Dis 166, 1177–1180Google Scholar
  49. 49.
    Plikaytis, B. B, Eisenach, K D., Crawford, J T, and Shinnick, T M (1991) Differentiation of Mycobacterium tuberculosis and Mycobacterium bovis BCG by a polymerase chain reaction assay. Mol Cell Probes.5, 215–219PubMedCrossRefGoogle Scholar
  50. 50.
    Sritharan, V and Barker, R. (1991) A simple method for diagnosing M tuberculosisinfection in clinical samples using PCR. Mol Cell Probes 5, 385–395PubMedCrossRefGoogle Scholar
  51. 51.
    Suzuki, Y, Nagata, A., Ono, Y, and Yamada, T. (1988) Complete sequence of the 16S rRNA gene of Mycobacterium bows BCG. J Bacteriol 170, 2886–2889PubMedGoogle Scholar
  52. 52.
    Kolk, A H J, Noordhoek, G T, De Leeuw, O., Kuijper, S., and van Embden, J.D. A (1994) Mycobacterium smegmatis strain for detection of Mycobacterium tuberculosis by PCR used as internal control for inhibition of amplification by PCR used as internal control for inhibition of amplification and for quantification of bacteria J Clin Microbiol 32, 1354–1356PubMedGoogle Scholar
  53. 53.
    Kox, L. F. F, Rhientong, D, Medo Miranda, A, Udomsantisuk, N., Ellis, K., van Leeuwen, J, van Heusden, S, Kuijper, S., and Kolk, A H. J. (1994) A more reliable PCR for detection of Mycobacterium tuberculosis in clinical samples J Clin Microbiol 32, 672–678PubMedGoogle Scholar
  54. 54.
    Victor, T., du Toit R., and van Helden, P. D. (1992) Purification of sputum samples through sucrose improves detection of Mycobacterium tuberculosis by polymerase chain reaction J Clin Microbiol 30, 1514–1517PubMedGoogle Scholar
  55. 55.
    Buck, G. E., O’Hara, L. C, and Summergill, J T. (1992) Rapid, simple method for treating clinical specimens containing Mycobacterium tuberculosis to remove DNA for polymerase chain reaction.J. Clin. Microbiol. 30, 1331–1334PubMedGoogle Scholar
  56. 56.
    Carpentier, E, Drouillard, B., Dailloux, M, Moingard, D, Vallee, E, Dutilh, B, Maugein, J, Bergogne-Berezin, E, and Carbonnelle, B. (1995) Diagnosis of tuberculosis by amplicor Mycobacterium tuberculosistest. a multicenter study J. Clin Microbiol 33, 310–3110Google Scholar
  57. 57.
    Dilworth, J P, Goyal, M., Young, D B., and Shaw, R. J. (1996) Comparison of polymerase chain reaction for IS6110 and Amplicor in the diagnosis of tuberculosis Thorax. 51, 320–322PubMedCrossRefGoogle Scholar
  58. 58.
    Vlaspolder, F, Singer, P, and Roggeveen, C (1995) Diagnostic value of an amplification method (Gen-Probe) compared with that of culture for diagnosis of tuberculosis J Clan Microbiol 33, 2699–2703Google Scholar
  59. 59.
    Vuorinen, P., Miettinen, A., Vuento, R, and Hallstrom, O. (1995) Direct detection of Mycobacterium tuberculosis complex in respiratory specimens by Gen-Probe amplified Mycobacterium tuberculosis direct test and Roche Amplicor Mycobacterium tuberculosis test J Clin Microbiol 33, 1856–1859.PubMedGoogle Scholar
  60. 60.
    Goto, K, Okuzmi, K, Sakai, Y, Takewaki, S, Tachikawa, N, Iwamoto, A, Kimura, S., and Shimada, K (1995) Comparison of amplified Mycobacterium tuberculosis direct test (MTD), amplicor mycobacteria kit (Amphcor) and PCR for detection of Mycobactertum tuberculosis in clinical specimens Kansenshogaku Zasshi 69, 539–545PubMedGoogle Scholar
  61. 61.
    Rogall, T, Flohr, T, and Bottger, E C. (1990) Differentiation of Mycobacterium species by direct sequencing of amplified DNA J Gen Microbiol 136, 1915–19200PubMedGoogle Scholar
  62. 62.
    Kirschner, P, Rosenau, J, Springer, B, Teschner, K, Feldmann, K, and Bottger, E C (1996) Diagnosis of mycobacterial infections by nucleic acid amplification 18 month prospective study J Clin Microbrol 34, 304–312Google Scholar
  63. 63.
    Bloch, A B, Cauthen, G M, Onorato, I M, Dansbury, K G, Kelly, G D, Driver, C R., and Snider, D E, Jr (1994) Nationwide survey of drug resistant tuberculosis in the United States JAMA 271, 665–671PubMedCrossRefGoogle Scholar
  64. 64.
    Friden, T R, Sterling, T, Pablos-Mendez, A, Kilburn, J O, Cauthen, G M, and Dooley, S W (1993) The emergence of drug resistant tuberculosis in New York city N Engl J Med 328, 521–526.Google Scholar
  65. 65.
    Musser, J M. (1995) Antimicrobial agent resistance in mycobacteria molecular genetic insights. Clin Microbiol Rev. 8, 496–514PubMedGoogle Scholar
  66. 66.
    Fischl, M A, Uttamchandam, R B., Daikos, G L, Poblete, R B, Moreno, J N, Reyes, R.R., Boota, L.M, Thompson, L M., Cleary, T J., and Lai, S (1992)An outbreak of tuberculosis caused by multiple drug resistant tubercle bacilli among patients with HIV Infection Ann Intern Med 117, 177–183.PubMedGoogle Scholar
  67. 67.
    Honore, N and Cole, S T (1993) Molecular basis of rifampin resistance in Mycobacterium Ieprae Antimicrob. Agents. Chemother 37, 414–418.Google Scholar
  68. 68.
    Miller, L P, Crawford, J T, and Shininck, T M (1994) The rpoB gene of Mycobacterium tuberculosis Antimicrb. Agents Chemother 38, 313–319Google Scholar
  69. 69.
    Kaput, V, Lt, L L., Iordanescu, S, Hammick, M R., Wanger, A., Krieswirth, B N, and Musser, J M (1994) Characterization by automated DNA sequencing of mutations in the gene (rpoB) encoding the RNA polymerase B subunit in rifampin resistant Mycobacterium tuberculosis strains from New York City and Texas. J Clin Microbiol 32, 1095–1098Google Scholar
  70. 70.
    Telenti, A., Imboden, P., Marchesi, F., Lowrie, D., Cole, S, Colston, M. J., Matter, L., Schopfer, K., and Bodner, T (1993) Detection of rifampicin resistance mutations in Mycobacteriu tuberculosis. Lancet 341, 805–811.CrossRefGoogle Scholar
  71. 71.
    Middlebrook, G. (1954) Isoniazld-resistance and catalase activity of tubercle bacilli Am Rev Tuberculosis 69, 47l–472Google Scholar
  72. 72.
    Hedgecock, L. and Faucher, I. O(1957) Relation of pyrogallol-peroxidase activity to isomazid resistance in Mycobacterium tuberculosis Am Rev Tuberc 75, 670–674.Google Scholar
  73. 73.
    Zhang, Y, Heym, B, Allen, B, Young, D., and Cole, S (1992) The catalase-peroxidase gene and isomazid resistance to Mycobacterium tuberculosis Nature 358, 591–593.Google Scholar
  74. 74.
    Heym, B., Zhang, Y, Poulet, S, Young, D, and Cole, S T. (1993) Characterization of the katG gene encoding a catalase peroxidase required for the Isoniazid susceptibility of Mycobacterium tuberculosis. J. Bacteriol 175, 4255–4259.PubMedGoogle Scholar
  75. 75.
    Zhang, Y. and Young, D (1993) Molecular mechanisms of isoniazid: a drug at the front line of tuberculosis control Trends Microbiol 1, 109–113PubMedCrossRefGoogle Scholar
  76. 76.
    Heym, B., Alzan, P. M, Honore, N, and Cole, S. T. (1995) Missense mutations in the catalase peroxidase gene, katG, are associated with isoniazid resistance in Mycobacterium tuberculosis Mol Microbiol 15, 235–245.Google Scholar
  77. 77.
    Altamirano, M, Marostenmaki, J., Wong, A., FitzGerald, M., Black, W A., and Smith, J A (1994) Mutations in the catalase-peroxidase gene from isoniazid-resistant Mycobacterium tuberculosis isolates.J Infect Dio 169, 1162–1165Google Scholar
  78. 78.
    Banerjee, A., Dubnau, E, Quemard, A, Balasubramanian, V., Um, K. S, Wilson, T., Collins, D, deLisle, G, and Jacobs, W. R, Jr (1994) inhA, a gene encoding a target for isomazid and ethlonamide in Mycobacterium tuberculosis.Science 263, 227–230PubMedCrossRefGoogle Scholar
  79. 79.
    Musser, J. M, Kapur, V, Williams, D. L, Kreisworth, B N., van Sooloingen, D, and van Embden, J D.A (1996) Characteisation of the catalase peroxidase gene (katG) and inhA locus in isomazid 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.PubMedGoogle Scholar
  80. 80.
    Heym, B., Honore, N., Truffot-Pernot, C., Banerjee, A., Schurra, C., Jacobs, W. R., Jr., van Embden, J D. A., Grosset, J H., and Cole, S. T (1994) Implications of multidrug resistance for the future of short course chemotherapy of tuberculosis: a molecular study. Lancet 30, 277–279.Google Scholar
  81. 81.
    Wilson, T. M. and Collins, D. M. (1996) ahpC, a gene involved in isomazid resistance of the Mycobacterium tuberculosis complex Mol.Microbiol 19, 1025–1034Google Scholar
  82. 82.
    Honore, N. and Cole, S. T. (1994) Streptomycin resistance in mycobacteria Antimicrob. Agents. Chemother 38, 238–242.Google Scholar
  83. 83.
    Nair, J., Rouse, D. A, Bai, G H, and Morris, S. L (1993) The rpsL gene and streptomycin resistance in single and multiple drug-resistant strains of Mycobacterium tuberculosis. Mol Microbiol. 10, 521–527.PubMedCrossRefGoogle Scholar
  84. 84.
    Finken, M., Kirschner, P., Meier, A., Wrede, A., and Bottger, E. C. (1993) Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterationsof the rtbosomal protein S12 gene and pomt mutations within a functional 16S ribosomal RNA pseudoknot Mol Microbiol 9, 1239–1246PubMedCrossRefGoogle Scholar
  85. 85.
    Takiff, H. E, Guerrero, C, Phillip, W,et al (1993) Mutations in the gyrase A gene (gyrA) of Mycobacterium tuberculosis confer resistance to fluoroqumolones in “Program and abstracts of the 33rd international conference on Antimicrobial Agents and Chemotherapy” (New Orleans) abstr 1092 American Society for Microbilogy Washington DCGoogle Scholar
  86. 86.
    Takiff, H. E, Cimino, M, Musso, M C., Weisbrod, T, Martinez, R, Delgado, M B, Salazar, L, Bloom, B R.,and Jacobs, W R, Jr (1996) Efflux pump of the protein antiporter family confers low level fluoroquinolone resistance in Mycobacterium smegmatis Proc Nat1 Acad Scl USA 93, 362–366CrossRefGoogle Scholar
  87. 87.
    Kawa, D E., Pennell, D R, Kubista, L N., and Schell, R F (1989) Development of a rapid method for determining the susceptibiliy of Mycobacterium tuberculosis to isoniazid using the Gen-Probe DNA hybridization system Antimicrob Agents Chemother 33, 100–1005Google Scholar
  88. 88.
    Jacobs, W R, Jr, Barletta, R G., Udani, R., Chan, J., Kalkut, G, Sosne, G, Ketser, T., Sarkis, G J., Hatfull, G. A., and Bloom, B R. (1993) Rapid assesment of drug susceptibilmes of Mycobacterium tuberculosis by means of luciferase reporter phages. Science 260, 819–822.PubMedCrossRefGoogle Scholar
  89. 89.
    Plikaytis, B B, Marden, J L, Crawford, J T, Woodley, C. L, Butler, W R, and Shininck, T. M (1994) Multiplex PCR assay specific for the multidrug resistant strain W of Mycobacterium tuberculosis J Clin Microbiol 32, 1542–1546PubMedGoogle Scholar
  90. 90.
    Nolan, C M, Elarth, A. M., Barr, H, Saeed, A M, and Risser, D R, (1991) An outbreak of tuberculosis in a shelter for homeless men. a description of its evolution and control Am Rev Respir Dis 143, 257–2PubMedGoogle Scholar
  91. 91.
    Reves, R, Blakey, D, Snider, D. E, Jr., and Farer, L S. (1981) Transmission of multiple drug-resistant tuberculosis: report of a school and community outbreak. Am J Epidemiol 113, 423–435.PubMedGoogle Scholar
  92. 92.
    Snider, D. E, Jones, W. D, and Good, R C. (1994) The usefulness of phage typing Mycobacterium tuberculosis isolates Am Rev Respir Dis 130, 1095–1099Google Scholar
  93. 93.
    Millership, S E. and Want, S (1992) Whole cell protein electrophoresis for typing Mycobacterium tuberculosis J Ch Microbiol 30, 2784–2787Google Scholar
  94. 94.
    Zamuddin, Z F and Dale, J. W (1990) Does Mycobacterium tuberculosis have plasmids? Tubercle 71, 43–49CrossRefGoogle Scholar
  95. 95.
    Hoffner, S. E., Svenson, S A., Norberg, R, Dias, F., Ghebremichael, S., and Kallenius, G (1993) Biochemical heterogenity of Mycobacterium tuberculosis complex isolates in Guinea-Bissau J Clin Microbiol 31, 2215–2217.PubMedGoogle Scholar
  96. 96.
    Wasem, C F., McCarthy, C M, and Murray, L W (1991) Multilocus enzyme electrophoresis analysis of the Mycobacterium avium complex and other myco-bacteria. J, Clin. Microbiol 29, 264–271Google Scholar
  97. 97.
    Imeda, T. (1985) DNA relatedness among selected strains of Mycobacterium tuberculosis, Mycobacterium bovis BCG, Mycobacterium microti and Mycobacterium africanum. Int J. Syst. Bacteriol. 35, 147–150CrossRefGoogle Scholar
  98. 98.
    Collins, D M and deLisle, G. W. (1985) DNA restriction endonuclease analysis of Mycobacterium bovis and other members of the tuberculosis complex J Clin Microbiol 21, 562–564.PubMedGoogle Scholar
  99. 99.
    Elsenach, K. D., Crawford, J T., and Bates, J H (1986) Genehc relatedness among strams of the Mycobacterium tuberculosis complex. Am Rev Respir Dis 133, 1065–1068Google Scholar
  100. 100.
    Small, P M. and vanEmbden, J D A (1994) Molecular epidemiology of tuberculosls in “Tuberculosis, pathogenesls, protection and control” (Bloom, B. R., ed ), ASM, Washington, D. C, p 569–582Google Scholar
  101. 101.
    Groenen, P M.A., vanBunchoten, A. E., vanSoolligen, D., and vanEmbden, J D A (1993) Nature of DNA polymorphism in the direct repeat cluster of Mycobacterium tuberculosis application for strain differentiation by a novel method Mel Microbiol 105, 1057–1065.CrossRefGoogle Scholar
  102. 102.
    Hermans, P. W., vanSooligen, D, and vanEmbden, J. D. (1992) Characterization of a major polymorphic tandem repeat in Mycobacterium kansasu and Mycobacterium gordonae. J Bacteriol. 174, 4157–4165.Google Scholar
  103. 103.
    Ross, C., Raios, K, Jackson, K, and Dwyer, B. (1992) Molecular cloning of a highly repeated element from Mycobacterium tuberculosis and its use as an epidemiological tool J Clin Microbiol 30, 942–946PubMedGoogle Scholar
  104. 104.
    Wild, I J F., Werely, C, Beyers, N., Donald, P., and Helden, P. D (1994) Oligonucleotide (GTG)5 as a marker for strain identification in Mycobacterium tuberculosis J Clin Microbiol 32, 1318–1321Google Scholar
  105. 105.
    van Embden, J D., Cave, M D, Crawford, J. T, Dale, J W, Eisenach, K D, Glcquel, B., Herman, P, Martin, C, McAdam, R., Shinnick, T M, and Small, P M (1993) Strain identification of Mycobacterium tuberculosis by DNA fingerprinting recommendations for a standardized methodology J Clin Microbiol 31, 406–409PubMedGoogle Scholar
  106. 106.
    Cave, M D, Eisenach, K D., McDermott, P. F., Bates, J. H., and Crawford, J. T (1991) IS6110 conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting. Mol. Cell Probes 5, 73–80PubMedCrossRefGoogle Scholar
  107. 107.
    Otal, I., Martin, C, Vincent-Levy-Frebault, V, Thierry, D., and Glcquel, B(1991) Restriction fragment length polymorphism analysis using IS6110 as an epidemiological marker in tuberculosis. J Clin Microbiol 29, 1252–1254.PubMedGoogle Scholar
  108. 108.
    van Soolingen, D, Hermans, P.W M, de Haas, P. E W, Soll, D R, and van Embden, J D. A. (1991) Occurence and stability of insertion sequences in Mycobacterium tuberculosis complex strains. evaluation of an insertion sequence dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J,Clin Microbiol. 29, 2578–2586Google Scholar
  109. 109.
    Godfrey-Faussett, P., Stoker, N. G., Scott, J A. G., Pasvol G, Kelly, P., and Clancy, L (1993) DNA fingerprints of Mycobacterium tuberculosis do not change during the development of rifampicin resistance Tubercle Lung Dis 74, 240–243CrossRefGoogle Scholar
  110. 110.
    Daley, C L., Small, P. M., Schecter, G. F., Schoolnik, G K., McAdam, R A, Jacobs, W. R, Jr, and Hopewell, P. C(1992) An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodefi-ciency virus. an analysis using restriction fragment length polymorphism N Engl J Med 326, 231–235PubMedCrossRefGoogle Scholar
  111. 111.
    Dwyer, B, Jackson, K., Ralos, K., Sievers, A, Wilshire, E., and Ross, B.(1993) DNA restriction fragment analysis to define an extended cluster of tuberculosis in homeless men and then associates J Infect Dis 167, 490–494PubMedGoogle Scholar
  112. 112.
    Edlin, B R., Tokars, J. I, Grieco, M. H, Crawford, J T., Williams, J, Sordillo, E M., Ong, K R, Kilburn, J. O, Dooley, S W., Castro, K G, Jarvis, W. R, and Holmberg, S D.(1992) An outbreak of multidrug resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. N Eng J Med 326, 1514–1521CrossRefGoogle Scholar
  113. 113.
    Goyal, M, Ormerod, L. P, and Shaw, R. J (1994) Epidemiology of an outbreak of drug resistant tuberculosis m the UK using restriction fragment length polymorphism Clin Sci, 86, 749–751PubMedGoogle Scholar
  114. 114.
    Small, P M, McClenny, N. B, Singh, S. P., Schoolink, G K, Tompkins, L. S, and Mickelsen, P. A(1993) Molecular strain typing of Mycobacterium tuberculosis to confirm cross-contamination in the mycobacteriology laboratory and modification of procedures to minimise occurence of false positive cultures J Clin Microbiol 32, 1677–1682Google Scholar
  115. 115.
    Small, P M, Shafer, R. W., Hopewell, P C, Singh, S. P, Murphy, M I, Desmond, E, Sierra, M F., and Schoolnick, G. K. (1993) Exogenous reinfection with multidrug resistant Mycobacterium tuberculosis in patients with advanced HIV infection N Eng J Med 328, 1137–1144CrossRefGoogle Scholar
  116. 116.
    Yang, Z H., Mtoni, I, Chonde, M., Mwasekaga, M., Fuursted, K, Askgard, D. S, Bennedsen, J., de Haas, P. E W., Soolingen, D, van Soolingen D, van Embden, J D A, and Andersen, A. B (1995) DNA fingerprinting and phenotyping of Mycobacterium tuberculosis isolates from human immunodeficiency virus (HIV)-seropositve and HIV-sernegative patients in Tanzania J Clin Microbiol 33, 1064–1069PubMedGoogle Scholar
  117. 117.
    Alland, D., Kalkut, G. E., Moss, A. R, McAdam, R. A., Hahn, J A., Bosworth, W, Drucker, E, and Bloom, B R. (1994) Transmission of tuberculosis in New York City an analysis by DNA fingerprinting and conventional epidemiology N Eng J Med 330, 1703–1708CrossRefGoogle Scholar
  118. 118.
    Small, P. M, Hopewell, P C, Singh, S P., Antonio, P., Parsonnet, J., Ruston, D C, Schecter, G. F, Daley, C L, and Schoolnik, G. K (1994) The epidemiology of tuberculosis in San Francisco: a population based study using conventional and molecular methods. N Engl J Med 330, 1703–1709PubMedCrossRefGoogle Scholar
  119. 119.
    Genewin, A., Telenti, A, Bernasconi, C., Mordasini, C, Weiss, S., Maurer, A., Reider, H. L, Schopfer, K., and Bodmer, T. (1993) Molecular approach to identify route of transmission of tuber culosis in the community Lancet 342, 841–844.CrossRefGoogle Scholar
  120. 120.
    vanSoolingen D, Qian, L, de Haas, P. E. W., Douglas, J. T., Tarore, H., Portaels, F., Qing, H Z., Enkhasaikan, D, Nymadawa, P, and van Embden, J D A. (1995) Predominance of a single genotype of Mycobacterium tuberculosis in countries of East Asia. J Clin Microbiol 33, 3234–3238PubMedGoogle Scholar
  121. 121.
    van Soolingen, D., de Haas, P E.W, Hermans, P. W. M, Groenen, P. M A., and van Embden, J.D A. (1993) Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis J Clin. Micribiol. 31, 1987–1995.Google Scholar
  122. 122.
    Zhang, Y, Mazurek, G. H., Cave, M D, Eisenach, K. D., Pang, Y, Murphy, D T., and Wallace, R J., Jr. (1992) DNA polymorphism in strains of Mycobacterium tuberculosis analysed by pulsed field gel electrophoresis: a tool for epidemiology.J Clin Microbiol 30, 1551–1556.PubMedGoogle Scholar
  123. 123.
    Palittapongarnpim, P, Chomyc, S, Fanning, A., and Kummoto, D. (1993) DNA fingerprinting of Mycobacterium tuberculosis isolates by ligation mediated polymerase chain reaction Nucleic Acids Res. 21, 761–762PubMedCrossRefGoogle Scholar
  124. 124.
    Linton, C. J., Jalal, H., Leeming, J. P., and Miller, M. R. (1994) Rapid discrimination of Mycobacterium tuberculosis strains by random amplified polymorphic DNA analysis J Clin Microbiol 32, 2169–2174.PubMedGoogle Scholar
  125. 125.
    Abed, Y., Davin-Regli, A., Ballet, C.. and De Micco, P (1995) Efficient discrimination of Mycobacterium tuberculosis strains by 16S — 23S spacer region based random amplified polymorphic DNA analysis.J Clin Microbiol 33, 1418–1420PubMedGoogle Scholar
  126. 126.
    Haas, W H, Butler, W R, Woodley, C L, and Crawford, J T(1993) Mixed linker polymerase chain reaction. a new method for rapid fingerprinting of isolates of the Mycobacterium tuberculosis complex J Clin. Microbiol 31, 1293–1298PubMedGoogle Scholar
  127. 127.
    Ross, B C and Dwyer, B (1993) Rapid, simple method for typing isolates of Mycobacterium tuberculosis by using the polymerase chain reaction J Clin Microbiol 31, 329–334PubMedGoogle Scholar
  128. 128.
    Pilkaytis, B. B, Crawford, J. T, Woodley, C. L, Butler, W R, Eisenach, K. D, Cave, M. D., et al (1993) Rapid amplification based fingerprinting of Mycobacterium tuberculosis J Gen Microbiol. 139, 1537–15Google Scholar
  129. 129.
    Goyal, M., Young, D., Zhang, Y., Jenkins, P. A., and Shaw, R J. (1994) PCR amplification of variable sequence upstream of katG gene to subdivide strains of Mycobacterium tuberculosis complex. J Clin Microbiol 32, 3070–3071PubMedGoogle Scholar
  130. 130.
    Friedman, C. R., Stoeckle, M. Y., Johnson, W D, Jr, and Riley, L. (1995) Double-repetitive-element PCR method for subtyping Mycobacterium tuberculosis clinical isolates J Clin Microbiol 33, 1383–1384PubMedGoogle Scholar
  131. 131.
    Goyal, M, van Embden, J D A., Young, D B., and Shaw, R J (1995) Evaluation of spoligotyping as an epidemiological test in three different outbreaks of tuberculosis. Thorax 50 (Suppl 2), A35Google Scholar
  132. 132.
    Tenover, F C., Crawford, J. T, Huebner, R. E, Geiter, L. J., Horsburgh, C R., Jr, and Good, R C (1993) The resurgence of tuberculosis. is your laboratory ready? J Clin. Microbiol 31, 767–770PubMedGoogle Scholar
  133. 133.
    Bird, B. R., Denniston, M M., Huebner, R. E., and Good, R C (1996) Changing practices in Mycobacteriology: a follow up survey of state and territorial public health laboratories.J Clin Microbiol 34, 554–559.PubMedGoogle Scholar
  134. 134.
    Del Portillo, P., Murillo, A, and Patarroyo, M. E (1991) Amplification of a species specific DNA fragment of Mycobacterium tuberculosis and its possible use in diagnosis J Clin. Microbiol 29, 2163–2168.PubMedGoogle Scholar
  135. 135.
    De Beenhouwer, H, Lhiang, Z, Jannes, G, Mijs, W., Machtelinckx, L, Rossau, R., Traore, H., and Portaels, F. (1995) Rapid detection of rifampicin resistance in sputum and biopsy specimens from tuberculosis patients by PCR and line probe assay Tubercle. Lung Dis 76, 425–430.CrossRefGoogle Scholar
  136. 136.
    Goyal, M, Shaw, R. J, Baneqee, D. K, Coker, R. J., Robertson, B D, and Young, D. B (1997) Rapid detection of multidrug resistant tuberculosis Eur Respir J 10, 1120–1124.PubMedCrossRefGoogle Scholar
  137. 137.
    Kamerbeek, J, Schouls, L, Kolk, A, vanAgterveld, M, vanSoolingen, D, Kuijper, S, Banschoten, A., Molhuizen, H., Shaw, R., Goyal, M, and van Embden, J (1997) Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epiemiology J Clin Microbiol 35, 907–914PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1998

Authors and Affiliations

  • Madhu Goyal
    • 1
  • Douglas Young
    • 1
  1. 1.Imperial College School of MedicineSt. Mary’s CampusLondonUK

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