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Tuberculosis & Respiratory Diseases

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Vol.72 No.6
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pncA Mutations in the Specimens from Extrapulmonary Tuberculosis

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2012, v.72 no.6, pp.475-480
https://doi.org/10.4046/trd.2012.72.6.475



Cheah Yoke Kqueen (Jeju National University School of Medicine)

Hee-Youn Kim (Seoul National University College of Medicine)


Cheah, Y. K. , Hee-Youn, K. , & (2012). pncA Mutations in the Specimens from Extrapulmonary Tuberculosis. Tuberculosis & Respiratory Diseases, 72(6), 475-480, https://doi.org/10.4046/trd.2012.72.6.475
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Abstract

Background: Pyrazinamide (PZA) is an effective antitubercular drug that becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (PZase), encoded by mycobacterial pncA. A strong association was noted between the loss of PZase activity and PZA resistance. The causative organisms in extrapulmonary tuberculosis are rarely cultured and isolated. To detect pncA mutations in specimens from extrapulmonary tuberculosis as confirmative diagnosis of mycobacterial infection and alternative susceptibility test to PZA. Methods: Specimens were collected from clinically proven extrapulmonary tuberculosis. pncA was sequenced and compared with wild-type pncA. Results: pncA from 30 specimens from 23 donors were successfully amplified (56.6% in specimens, 59% in donors). Six mutations in pncA were detected (20.0% in amplified specimens, 26.1% in specimen donors) at nucleotide positions of 169, 248 and 419. The mutation at position 169 results in substitution of aspartic acid for histidine,a possible allelic variation of M. bovis that have intrinsic PZA resistance. The mutation at position 248 changes proline into arginine and that at position 419, arginine into histidine. Conclusion: DNA-based diagnosis using pncA may be simultaneously useful for the early diagnosis of mycobacterial infection and the rapid susceptibility to PZA in extrapulmonary tuberculosis. A potential implication of pncA allelic variation at 169 might be suggested as a rapid diagnostic test for M. bovis infection or Bacille Calmette-Guérin (BCG) reactivation.

keywords
Antitubercular Agents, Pyrazinamide, Tuberculosis, Amidohydrolases, Mycobacterium bovis

Reference

1.

1. Bass JB Jr, Farer LS, Hopewell PC, O'Brien R, Jacobs RF, Ruben F, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med 1994;149: 1359-74.

2.

2. 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;2:662-7.

3.

3. 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;78:117-22.

4.

4. Shim TS, Kim YW, Chin JY, Lim CM, Lee SD, Koh Y, et al. Detection of pyrazinamide-resistant Mycobacterium tuberculosis by PCR-SSCP of pncA gene. Tuberc Respir Dis 1998;45:1178-87.

5.

5. 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 Quebec, Canada. Antimicrob Agents Chemother 2000;44:528-32.

6.

6. Park SK, Lee JY, Chang CL, Lee MK, Son HC, Kim CM, et al. pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea. BMC Infect Dis 2001;1:4.

7.

7. Lee KW, Lee JM, Jung KS. Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea. J Korean Med Sci 2001;16:537-43.

8.

8. Hwang JY, Kwak KR, Park HK, Lee JS, Park SS, Kim YS, et al. Detection of pyrazinamide resisitance in Mycobacterium tuberculosis by sequencing of pncA gene. Tuberc Respir Dis 2001;50:94-105.

9.

9. Miyagi C, Yamane N, Yogesh B, Ano H, Takashima T. Genetic and phenotypic characterization of pyrazinamide- resistant Mycobacterium tuberculosis complex isolates in Japan. Diagn Microbiol Infect Dis 2004;48: 111-6.

10.

10. Ando H, Mitarai S, Kondo Y, Suetake T, Sekiguchi JI, Kato S, et al. Pyrazinamide resistance in multidrug- resistant Mycobacterium tuberculosis isolates in Japan. Clin Microbiol Infect 2010;16:1164-8.

11.

11. Kim HJ, Kwak HK, Lee J, Yun YJ, Lee JS, Lee MS, et al. Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea. Int J Tuberc Lung Dis 2012;16:98-103.

12.

12. Wayne LG. Simple pyrazinamidase and urease tests for routine identification of mycobacteria. Am Rev Respir Dis 1974;109:147-51.

13.

13. Kempsell KE, Cox CJ, McColm AA, Bagshaw JA, Reece R, Veale DJ, et al. Detection of Mycobacterium tuberculosis group organisms in human and mouse joint tissue by reverse transcriptase PCR: prevalence in diseased synovial tissue suggests lack of specific association with rheumatoid arthritis. Infect Immun 2001;69: 1821-31.

14.

14. Kempsell KE, Cox CJ, Hurle M, Wong A, Wilkie S, Zanders ED, et al. Reverse transcriptase-PCR analysis of bacterial rRNA for detection and characterization of bacterial species in arthritis synovial tissue. Infect Immun 2000;68:6012-26.

15.

15. Malaviya AN, Kotwal PP. Arthritis associated with tuberculosis. Best Pract Res Clin Rheumatol 2003;17:319- 43.

16.

16. Yoon HJ, Song YG, Park WI, Choi JP, Chang KH, Kim JM. Clinical manifestations and diagnosis of extrapulmonary tuberculosis. Yonsei Med J 2004;45:453-61.

17.

17. Cho EH, Bae HK, Kang SK, Lee EH. Detection of isoniazid and rifampicin resistance by sequencing of katG, inhA, and rpoB genes in Korea. Korean J Lab Med 2009;29:455-60.

18.

18. Aslanzadeh J, de la Viuda M, Fille M, Smith WB, Namdari H. Comparison of culture and acid-fast bacilli stain to PCR for detection of Mycobacterium tuberculosis in clinical samples. Mol Cell Probes 1998;12: 207-11.

19.

19. Kim BJ, Lee KH, Park BN, Kim SJ, Bai GH, Kim SJ, et al. Differentiation of mycobacterial species by PCRrestriction analysis of DNA (342 base pairs) of the RNA polymerase gene (rpoB). J Clin Microbiol 2001;39: 2102-9.

20.

20. Yun YJ, Lee KH, Haihua L, Ryu YJ, Kim BJ, Lee YH, et al. Detection and identification of Mycobacterium tuberculosis in joint biopsy specimens by rpoB PCR cloning and sequencing. J Clin Microbiol 2005;43:174-8.

21.

21. Kim SY, Kim HJ, Kim CK, Yoon HR, Bae HG, Lee SH, et al. The recent status of multidrug- and extensively drug-resistant tuberculosis in Korea. Tuberc Respir Dis 2010;68:146-54.

22.

22. Choi JH, Lee KW, Kang HR, Hwang YI, Jang S, Kim DG, et al. Clinical efficacy of direct DNA sequencing analysis on sputum specimens for early detection of drug-resistant Mycobacterium tuberculosis in a clinical setting. Chest 2010;137:393-400.

23.

23. Chan RC, Hui M, Chan EW, Au TK, Chin ML, Yip CK, et al. Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. J Antimicrob Chemother 2007;59:866-73.

24.

24. Konno K, Nagayama H, Oka S. Nicotinamidase in Mycobacteria: a method for distinguishing bovine type tubercle bacilli from other Mycobacteria. Nature 1959; 184(Suppl 22):1743-4.

25.

25. Kidane D, Olobo JO, Habte A, Negesse Y, Aseffa A, Abate G, et al. Identification of the causative organism of tuberculous lymphadenitis in ethiopia by PCR. J Clin Microbiol 2002;40:4230-4.

26.

26. de Souza Campos Fernandes RC, Medina-Acosta E. BCG-itis in two antiretroviral-treated HIV-infected infants. Int J STD AIDS 2010;21:662-3.

27.

27. Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's disease. J Crohns Colitis 2010;4:603-5.

28.

28. Thamthitiwat S, Marin N, Baggett HC, Peruski LF, Kiatkulwiwat W, Panumatrasmee V, et al. Mycobacterium bovis (Bacille Calmette-Guerin) bacteremia in immunocompetent neonates following vaccination. Vaccine 2011;29:1727-30.

29.

29. Kim SH, Kim SY, Eun BW, Yoo WJ, Park KU, Choi EH, et al. BCG osteomyelitis caused by the BCG Tokyo strain and confirmed by molecular method. Vaccine 2008;26:4379-81.

30.

30. Santos A, Dias A, Cordeiro A, Cordinhã C, Lemos S, Rocha G, et al. Severe axillary lymphadenitis after BCG vaccination: alert for primary immunodeficiencies. J Microbiol Immunol Infect 2010;43:530-7.

31.

31. Jou R, Huang WL, Su WJ. Tokyo-172 BCG vaccination complications, Taiwan. Emerg Infect Dis 2009;15:1525-6.

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