Automated liquid culture system misses isoniazid heteroresistance in Mycobacterium tuberculosis isolates with mutations in the promoter region of the inhA gene
Automated liquid culture system misses isoniazid heteroresistance in Mycobacterium tuberculosis isolates with mutations in the promoter region of the inhA gene
复制标题
自动化液体培养系统遗漏了 inhA 基因启动子区突变的结核分枝杆菌分离株中的异烟肼异抗性
DOI：
10.1007/s10096-014-2262-0
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发表时间：
2014
影响因子：
4.5
通讯作者：
Yong Zhao
中科院分区：
文献类型：
--
作者：
Wentao Bao;Jie Lu;Yufeng Wang;Y. Pang;Yong Zhao
结核分枝杆菌分离株的异质耐药性仍然是检测耐药性的表型药物敏感性测试 (DST) 方法的主要挑战。本研究的目的是探讨表型 DST 方法识别结核分枝杆菌异烟肼 (INH) 异质耐药性的能力。我们发现，如果存在 0.5% 具有 katG 和 oxyR-ahpC 区域突变的耐药细菌，肉汤稀释法就能够检测到 INH 耐药性，而对于带有 inhA 突变的 INH 耐药菌株，检测限范围为 1% 至 10%，这与不同的突变类型有关。此外，由于 katG 突变，MGIT DST 能够发现推荐的 1% INH 耐药性。相比之下，MGIT DST 在含有 20% 具有 inhA 突变的耐药细菌的悬浮液中检测到耐药性。统计分析显示，肉汤稀释法检测异质抗性的能力优于MGIT DST（p = 0.004）。当我们进一步两两比较根据不同突变位点检测异抗性的两种方法时，肉汤稀释法发现inhA突变导致的异抗性比MGIT DST更多（p = 0.001），而katG和oxyR-ahpC突变的差异均不具有统计学意义（p > 0.05）。总之，我们的研究结果表明，MGIT DST 未能检测到 inhA 启动子区域发生突变的结核分枝杆菌分离株中的 INH 异质抗性。此外，肉汤稀释法在发现INH异质抗性方面比MGIT DST更敏感，表明该方法可作为检测结核分枝杆菌异质抗性的替代方法。
Heteroresistance in Mycobacterium tuberculosis isolates remains the major challenge for phenotypic drug susceptibility testing (DST) methods to detect drug resistance. The aim of this study was to investigate the abilities of phenotypic DST methods to identify the isoniazid (INH) heteroresistance in M. tuberculosis. We found that the broth dilution method was able to detect INH resistance if 0.5 % resistant bacteria with mutations in the katG and oxyR-ahpC regions were present, while the detection limit ranged from 1 to 10 % for the INH-resistant strains harboring inhA mutations, which was associated with the different mutant types. Additionally, MGIT DST was able to find the recommended 1 % INH resistance due to katG mutations. In contrast, MGIT DST detected resistance in suspensions with 20 % resistant bacteria with inhA mutations. Statistical analysis revealed that the ability of the broth dilution method to detect heteroresistance was better than that of the MGIT DST (p = 0.004). When we further pairwise compared the two methods for detecting heteroresistance according to different mutant loci, the broth dilution method found more heteroresistance due to inhA mutations than MGIT DST (p = 0.001), while the differences for katG and oxyR-ahpC mutations were both not statistically significant (p > 0.05). In conclusion, our findings demonstrate that MGIT DST fails to detect INH heteroresistance in M. tuberculosis isolates with mutations in the promoter region of inhA. In addition, the broth dilution method is more sensitive than MGIT DST in finding INH heteroresistance, indicating that this method may serve as an alternative method to detect the heteroresistance of M. tuberculosis.
影响因子：
11.4
作者：
Mueller, Borna;Borrell, Sonia;Rose, Graham;Gagneux, Sebastien
通讯作者：
Gagneux, Sebastien