Huang Hairong, Jin Qi, Ma Yu, Chen Xi, Zhuang Yuhui
Beijing Tuberculosis & Thoracic Tumor Institute, Tongzhou Qu, Beijing, People's Republic of China.
Tuberculosis (Edinb). 2002;82(2-3):79-83. doi: 10.1054/tube.2002.0326.
The objective of this study was for the elucidation of the characteristics of the rpoB gene mutation in rifampicin (RIF)-resistant Mycobacterium tuberculosis strains isolated in China. The rifampicin resistance determination regions (RRDR) of the rpoB genes of 242 M. tuberculosis strains were sequenced, including 193 RIF-resistant, 46 RIF-sensitive clinical isolates and three manually induced RIF-resistant tuberculosis strains. Mutations in the 81 bp RRDR of the rpoB gene were identified in 89.6% (173/193) of RIF-resistant clinical isolates. No mutation was observed in RIF-sensitive strains. Ser531Leu mutations accounted for 46.1% (89/193) of RIF-resistant strains; the mutation frequency of 526-His was 17.6% (34/193) in RIF-resistant strains. Furthermore, a combination of 2-3 single-point mutations was observed in 24 RIF-resistant strains (12.4%; 24/193). Mutations in three manually induced RIF-resistant tuberculosis strains were located at codons 531 and 526, respectively. The results indicate that about 90% of rifampicin-resistant M. tuberculosis strains isolated in China had rpoB mutations;531-Ser and 526-His were the most common positions substituted; high-level rifampicin-resistant strains had a higher frequency of 531-Ser mutations than low-level rifampicin-resistant strains. Sequencing analysis of the 81 bp fragment in the rpoB gene is useful in predicting the rifampicin-resistant phenotype.
本研究的目的是阐明在中国分离出的耐利福平（RIF）结核分枝杆菌菌株中rpoB基因突变的特征。对242株结核分枝杆菌菌株的rpoB基因的利福平耐药决定区（RRDR）进行了测序，其中包括193株耐RIF菌株、46株RIF敏感临床分离株和3株人工诱导的耐RIF结核菌株。在89.6%（173/193）的耐RIF临床分离株中鉴定出rpoB基因81 bp RRDR中的突变。在RIF敏感菌株中未观察到突变。Ser531Leu突变占耐RIF菌株的46.1%（89/193）；在耐RIF菌株中526-His的突变频率为17.6%（34/193）。此外，在24株耐RIF菌株（12.4%；24/193）中观察到2-3个单点突变的组合。3株人工诱导的耐RIF结核菌株中的突变分别位于密码子531和526处。结果表明，在中国分离出的约90%的耐利福平结核分枝杆菌菌株存在rpoB突变；531-Ser和526-His是最常见的替代位点；高水平耐利福平菌株中531-Ser突变的频率高于低水平耐利福平菌株。rpoB基因中81 bp片段的测序分析有助于预测利福平耐药表型。
