Zeng Mei-Chun, Jia Qing-Jun, Tang Lei-Ming
Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Hangzhou Center for Disease Control and Prevention, Hangzhou, China.
J Int Med Res. 2021 Mar;49(3):300060521997596. doi: 10.1177/0300060521997596.
The aim was to analyze genetic mutations in the gene of rifampin-resistant isolates (RIF-MTB) from Zhejiang, China.
We prospectively analyzed RIF-associated mutations in 13 rural areas of Zhejiang. Isolates were subjected to species identification, phenotype drug susceptibility testing (DST), DNA extraction, and gene sequencing.
A total of 103 RIF isolates were identified by DST (22 RIF only, 14 poly-drug resistant, 49 multidrug resistant, 13 pre-extensively drug resistant [pre-XDR], and 5 extensively drug resistant [XDR]) from 2152 culture-positive sputum specimens. Gene sequencing of showed that the most frequent mutation was S450L (37.86%, 39/103); mutations P280L, E521K, and D595Y were outside the rifampicin resistance-determining region (RRDR) but may be associated with RIF. Mutations associated with poly-drug resistant, pre-XDR, and XDR TB were mainly located at codon 445 or 450 in the RRDR.
The frequency of RRDR mutation in Zhejiang is high. Further studies are needed to clarify the relationships between RIF and the TTC insertion at codon 433 in the RRDR and the P280L and D595Y mutations outside the RRDR.
分析来自中国浙江的耐利福平结核分枝杆菌（RIF-MTB）菌株的基因突变情况。
我们对浙江13个农村地区的利福平相关突变进行了前瞻性分析。对分离菌株进行菌种鉴定、表型药敏试验（DST）、DNA提取和基因测序。
通过DST从2152份培养阳性痰标本中鉴定出103株利福平耐药菌株（仅耐利福平22株、耐多药14株、广泛耐药49株、预广泛耐药[pre-XDR]13株、广泛耐药[XDR]5株）。基因测序显示，最常见的突变是S450L（37.86%，39/103）；P280L、E521K和D595Y突变位于利福平耐药决定区（RRDR）之外，但可能与利福平耐药相关。与耐多药、pre-XDR和XDR结核病相关的突变主要位于RRDR的第445或450密码子处。
浙江RRDR突变频率较高。需要进一步研究以阐明利福平与RRDR中第433密码子处的TTC插入以及RRDR外的P280L和D595Y突变之间的关系。
