Minority Mycobacterium tuberculosis Genotypic Populations as an Indicator of Subsequent Phenotypic Resistance.
Minority Mycobacterium tuberculosis Genotypic Populations as an Indicator of Subsequent Phenotypic Resistance.
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DOI：
10.1165/rcmb.2019-0178le
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发表时间：
2019-11
影响因子：
6.4
通讯作者：
D. Engelthaler;E. Streicher;E. Kelley;C. Allender;Kristin Wiggins;Dulce J. Jiménez;D. Lemmer;E. Vittinghoff;G. Theron;F. Sirgel;R. Warren;J. Metcalfe
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文献类型：
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作者：
D. Engelthaler;E. Streicher;E. Kelley;C. Allender;Kristin Wiggins;Dulce J. Jiménez;D. Lemmer;E. Vittinghoff;G. Theron;F. Sirgel;R. Warren;J. Metcalfe
在可预见的未来，治疗期间获得性耐药仍将是广泛耐药结核病（XDR-TB）流行的主要驱动因素（1）。传统的基于培养的结核分枝杆菌（M.tb）表型药敏试验（DST）是在20世纪60年代构思的，在许多地区是费力的，稀缺的，太慢的临床决策。现有的商业分子TB诊断测试在几天内提供结果，但只能检测总结核分枝杆菌种群的5-65%以上的耐药亚群（2-4）。我们最近开发了一种新的靶向下一代测序（NGS）方法（单分子重叠读取[SMOR]），其能够辨别0.1%至5%之间的低水平少数抗性群体（即，微异源耐药性），用于异烟肼、利福平、氟喹诺酮类（FQs）、二线注射剂（SLI）和吡嗪酰胺（基因katG和inhA/inhA启动子; rpo B; gyrA/B; rrs;和pncA）（分别为5、6）。我们推测，在临床实践中，基因型微异源耐药可能先于表型耐药的获得。
Acquired resistance during treatment will remain a principal driver of the extensively drug-resistant tuberculosis (XDR-TB) epidemic into the foreseeable future (1). Conventional culture-based phenotypic drug-susceptibility testing (DST) for Mycobacterium tuberculosis (M.tb) as conceived in the 1960s is laborious, scarce in many regions, and too slow for clinical decision-making. Existing commercial molecular TB diagnostic tests provide results within days but can only detect resistant subpopulations greater than 5–65% of the total M.tb population (2–4). We recently developed a novel targeted next-generation sequencing (NGS) approach (Single Molecule-Overlapping Reads [SMOR]) that is able to discern low-level minority resistant populations between 0.1% and 5% (i.e., microheteroresistance) for isoniazid, rifampin, fluoroquinolones (FQs), second-line injectables (SLIs), and pyrazinamide (genes katG and inhA/inhA promoter; rpoB; gyrA/B; rrs; and pncA, respectively) (5, 6). We hypothesized that genotypic microheteroresistance may precede the acquisition of phenotypic drug resistance in clinical practice.