pncA Mutations in the Specimens from Extrapulmonary Tuberculosis

Tuberculosis and Respiratory Diseases

article

Jaechun Lee¹  Yeo-Jun Yun²  Cheah Yoke Kqueen¹  Jong Hoo Lee¹  Hee-Youn Kim²  Young Ree Kim¹  Yoon-Hoh Kook²  Keun Hwa Lee¹ 

[1] Jeju National University School of Medicine;Department of Microbiology and Immunology, Seoul National University College of Medicine

关键词: Antitubercular Agents;    Pyrazinamide;    Tuberculosis;    Amidohydrolases;    Mycobacterium bovis;   

DOI  :  10.4046/trd.2012.72.6.475

学科分类：医学（综合）

来源: The Korean Academy of Tuberculosis and Respiratory Diseases

【 摘 要 】

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.

【 授权许可】

CC BY-NC