- 作者: Ming-Chih Yu, Ching-Sheng Hung, Chun-Kai Huang, Cheng-Hui Wang, Yu-Chih Liang & Jung-Chun Lin
- 作者服務機構: 1.Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 2.Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 3.Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 4.School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan 5.School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Background
With the advancement of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been deployed to a wide range of clinical scenarios. Rapid and accurate classification of drug-resistant Mycobacterium tuberculosis (MTB) would be advantageous in reducing the amplification of additional drug resistance and disease transmission.
Methods
In this study, a long-read sequencing approach was subjected to the whole-genome sequencing of clinical MTB clones with susceptibility test profiles, including isoniazid (INH) susceptible clones (n = 10) and INH resistant clones (n = 42) isolated from clinical specimens. Non-synonymous variants within the katG or inhA gene associated with INH resistance was identified using Nanopore sequencing coupled with a corresponding analytical workflow.
Results
In total, 54 nucleotide variants within the katG gene and 39 variants within the inhA gene associated with INH resistance were identified. Consistency among the results of genotypic profiles, susceptibility test, and minimal inhibitory concentration, the high-INH resistance signature was estimated using the area under the receiver operating characteristic curve with the existence of Ser315Thr (AUC = 0.822) or Thr579Asn (AUC = 0.875).
Conclusions
Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones. - 中文關鍵字:
- 英文關鍵字: : InhA, Isoniazid, KatG, MinION, Mycobacterium tuberculosis