Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China
Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China
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DOI：
10.1128/aac.02358-15
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发表时间：
2016-05-01
影响因子：
4.9
通讯作者：
Shen, A-dong
中科院分区：
文献类型：
--
作者：
Li, Qin-jing;Jiao, Wei-wei;Shen, A-dong
结核分枝杆菌可通过 rpoB 基因突变获得对利福平 (RIF) 的耐药性。这通常伴随着适应性成本，然而，可以通过 rpoA 或 rpoC 基因的二次突变来减轻这种成本。本研究旨在鉴定中国北方临床结核分枝杆菌分离株中的rpoA和rpoC突变，以阐明它们在耐药结核病（TB）传播中的作用。研究收集包括 332 个 RIF 耐药菌株和 178 个 RIF 敏感菌株。大多数分离株属于北京基因型（95.3%，486/510株），非北京基因型菌株的rpoA或rpoC未发现突变。在北京基因型菌株中，27.8% (89/320) 的 RIF 抗性分离株携带 rpoA (n = 6) 或 rpoC (n = 83) 基因非同义突变。在新病例（P = 0.023）和具有 rpoB S531L 突变的菌株（P < 0.001）中，rpoC 突变的比例显着较高。此外，具有 rpoC 突变的多重耐药 (MDR) 菌株与 24 位点分枝杆菌散布重复单元可变数串联重复聚类显着相关 (P = 0.016)。总之，我们认为这些发现间接表明与 RIF 抗性和菌株适应性相关的特定突变之间存在上位相互作用，因此表明此类突变在 MDR 结核分枝杆菌菌株传播中的作用。
Mycobacterium tuberculosis can acquire resistance to rifampin (RIF) through mutations in the rpoB gene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in the rpoA or rpoC gene. This study aimed to identify rpoA and rpoC mutations in clinical M. tuberculosis isolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found in rpoA or rpoC of the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in the rpoA (n = 6) or rpoC (n = 83) gene. The proportion of rpoC mutations was significantly higher in new cases (P = 0.023) and in strains with the rpoB S531L mutation (P < 0.001). In addition, multidrug-resistant (MDR) strains with rpoC mutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat clustering (P = 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDR M. tuberculosis strains.