International Journal of Antimicrobial Agents
Volume 20, Issue 4 , Pages 275-281 , October 2002

Selection of in vitro mutants of pyrazinamide-resistant Mycobacterium tuberculosis

  • M. Bamaga

      Affiliations

    • Department of Infectious Diseases and Microbiology, Division of Investigative Science, Imperial College School of Medicine, SAF Building, 1st Floor, Exhibition Road, London SW7 2AZ, UK
    • ,
  • D.J.M. Wright

      Affiliations

    • Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, SAF Building 1st Floor, Exhibition Road, London SW7 2AZ, UK
    • Corresponding Author InformationCorresponding authors. Address: Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, SAF Building 1st Floor, Exhibition Road, London SW7 2AZ, UK. Tel.: +44-20-7594-3005; fax: +44-20-7594-3015
    • ,
  • H. Zhang

      Affiliations

    • Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, SAF Building 1st Floor, Exhibition Road, London SW7 2AZ, UK
    • Public Health and Clinical Microbiology Laboratory, Addenbrooke's Hospital, Cambridge, UK
    • Corresponding Author InformationCorresponding authors. Address: Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, SAF Building 1st Floor, Exhibition Road, London SW7 2AZ, UK. Tel.: +44-20-7594-3005; fax: +44-20-7594-3015

Received 31 May 2001 ,Accepted 23 March 2002.

References 

  1. Aquinas M. Short-course therapy for tuberculosis. Drugs. 1982;24:118–132
  2. Sun Z, Scorpio A, Zhang Y. The pncA gene from naturally pyrazinamide-resistant Mycobacterium avium encodes pyrazinamidase and confers pyrazinamide susceptibility to resistant M. tuberculosis complex organisms. Microbiology. 1997;143:3367–3373
  3. Zhang Y, Scorpio A, Nikaido H, Sun Z. Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J. Bacteriol. 1999;181:2044–2049
  4. Cheng SJ, Thibert L, Sanchez T, Heifets L, Zhang Y. pncA Mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: spread of a monoresistant strain in Que., Canada. Antimicrob. Agents Chemother. 2000;44:528–532
  5. Heifets LB, Flory MA, Lindholm-Levy PJ. Does pyrazinoic acid as an active moiety of pyrazinamide have specific activity against Mycobacterium tuberculosis?. Antimicrob. Agents Chemother. 1989;33:1252–1254
  6. Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR. Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat. Med. 2000;6:1043–1047
  7. Hirano K, Takahashi M, Kazumi Y, Fukasawa Y, Abe C. Mutation in pncA is a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis. Tuber Lung Dis. 1997;78:117–122
  8. Morlock GP, Crawford JT, Butler WR, et al.  Phenotypic characterization of pncA mutants of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2000;44:2291–2295
  9. Scorpio A, Lindholm-Levy P, Heifets L, et al.  Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 1997;41:540–543
  10. Scorpio A, Zhang Y. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat. Med. 1996;2:662–667
  11. Sachais BS, Nachamkindagger II, Mills JK, Leonard DG. Novel pncA mutations in pyrazinamide-resistant isolates of Mycobacterium tuberculosis. Mol. Diagn. 1998;3:229–231
  12. Lemaitre N, Sougakoff W, Truffot-Pernot C, Jarlier V. 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. 1999;43:1761–1763
  13. Mestdagh M, Fonteyne PA, Realini L, et al.  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. 1999;43:2317–2319
  14. Hou L, Osei-Hyiaman D, Zhang Z, Wang B, Yang A, Kano K. Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China. Epidemiol. Infect. 2000;124:227–232
  15. Mestdagh M, Realini L, Fonteyne PA, et al.  Correlation of pncA sequence with pyrazinamide resistance level in BACTEC for 21 Mycobacterium tuberculosis clinical isolates. Microb. Drug Resist. 2000;6:283–287
  16. Hannan MM, Desmond EP, Morlock GP, Mazurek GH, Crawford JT. Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States. J. Clin. Microbiol. 2001;39:647–650
  17. Peloquin CA, Jaresko GS, Yong CL, Keung AC, Bulpitt AE, Jelliffe RW. Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide. Antimicrob. Agents Chemother. 1997;41:2670–2679
  18. Conte JE, Golden JA, Duncan S, McKenna E, Zurlinden E. Intrapulmonary concentrations of pyrazinamide. Antimicrob. Agents Chemother. 1999;43:1329–1333
  19. Wayne LG. Simple pyrazinamidase and urease tests for routine identification of mycobacteria. Am. Rev. Respir. Dis. 1974;109:147–151
  20. Ausubel FM, Brent R, Kingston RE, et al.  In: Current protocols in molecular biology. New York: Wiley; 1994;
  21. Rinder H, Mieskes KT, Loscher T. Heteroresistance in Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis. 2001;5:339–345
  22. Kim BJ, Kim SY, Park BH, et al.  Mutations in the rpoB gene of Mycobacterium tuberculosis that interfere with PCR-single-strand conformation polymorphism analysis for rifampin susceptibility testing. J. Clin. Microbiol. 1997;35:492–494
  23. Pastor A, Peman J, Canton E. In-vitro postantibiotic effect of sparfloxacin and ciprofloxacin against Pseudomonas aeruginosa and Enterococcus faecalis. J. Antimicrob. Chemother. 1994;34:679–685
  24. Klemens SP, Sharpe CA, Cynamon MH. Activity of pyrazinamide in a murine model against Mycobacterium tuberculosis isolates with various levels of in vitro susceptibility. Antimicrob. Agents Chemother. 1996;40:14–16
  25. Marttila HJ, Marjamaki M, Vyshnevskaya E, et al.  pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from northwestern Russia. Antimicrob. Agents Chemother. 1999;43:1764–1766
  26. Sreevatsan S, Pan X, Zhang Y, Kreiswirth BN, Musser JM. Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. Antimicrob. Agents Chemother. 1997;41:636–640
  27. Boshoff HI, Mizrahi V. Expression of Mycobacterium smegmatis pyrazinamidase in Mycobacterium tuberculosis confers hypersensitivity to pyrazinamide and related amides. J. Bacteriol. 2000;182:5479–5485

PII: S0924-8579(02)00182-6

International Journal of Antimicrobial Agents
Volume 20, Issue 4 , Pages 275-281 , October 2002

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