Department of Pathology and Microbiology, University Teaching Hospital, Ministry of Health, Lusaka, Zambia.
Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan; Hokkaido University, The Global Station for Zoonosis Control, Sapporo, Japan.
J Glob Antimicrob Resist. 2020 Sep;22:302-307. doi: 10.1016/j.jgar.2020.02.026. Epub 2020 Mar 10.
It is established that resistance to rifampicin (RIF) in 90% of RIF-resistant Mycobacterium tuberculosis isolates is attributable to point mutations in the rpoB gene, whilst 50-95% of M. tuberculosis resistance to isoniazid (INH) is caused by mutations in the katG gene. However, the patterns and frequencies of mutations vary by geographical region. In Zambia, the genetic mechanisms of resistance of M. tuberculosis to RIF and INH were unreported before this study.
Using gene sequencing, the rpoB, katG and inhA genes of 99 multidrug-resistant M. tuberculosis (MDR-TB) and 49 pan-susceptible M. tuberculosis isolates stored at a tuberculosis reference laboratory from 2013 to 2016 were analysed and were compared with published profiles from other African countries.
Of the 99 MDR-TB isolates, 95 (96.0%) carried mutations in both rpoB and katG. No mutations were detected among the pan-susceptible isolates. The most common mutations among RIF- and INH-resistant isolates were in codon 531 of the rpoB gene (55.6%; 55/99) and codon 315 of the katG gene (94.9%; 94/99), respectively. Distinctly, katG mutations were predominantly high among Zambian isolates (96.0%) compared with other countries in the region.
Resistance-associated mutations to RIF and INH circulating in Zambia are similar to those reported globally, therefore these data validate the applicability of molecular diagnostic tools in Zambia. However, katG mutations were predominantly high among M. tuberculosis isolates in this study compared with other regional countries and might distinguish cross-boundary transmission of MDR-TB from other African nations.
已有研究证实，90%的耐利福平（RIF）结核分枝杆菌分离株的 RIF 耐药性归因于 rpoB 基因突变，而 50%-95%的结核分枝杆菌对异烟肼（INH）的耐药性是由 katG 基因突变引起的。然而，不同地理区域的突变模式和频率存在差异。在赞比亚，这项研究之前尚未报道结核分枝杆菌对 RIF 和 INH 的耐药性的遗传机制。
本研究使用基因测序技术，对 2013 年至 2016 年期间保存在结核病参考实验室的 99 株耐多药结核分枝杆菌（MDR-TB）和 49 株全敏感结核分枝杆菌分离株的 rpoB、katG 和 inhA 基因进行分析，并与来自其他非洲国家的已发表资料进行比较。
在 99 株 MDR-TB 分离株中，95 株（96.0%）在 rpoB 和 katG 基因中均携带突变。在全敏感分离株中未检测到突变。在 RIF 和 INH 耐药分离株中最常见的突变分别是 rpoB 基因 531 密码子（55.6%；55/99）和 katG 基因 315 密码子（94.9%；94/99）。值得注意的是，katG 突变在赞比亚分离株中明显更为常见（96.0%），高于该地区的其他国家。
在赞比亚流行的与耐药相关的 RIF 和 INH 突变与全球报道的相似，因此这些数据验证了分子诊断工具在赞比亚的适用性。然而，与其他地区国家相比，katG 突变在本研究的结核分枝杆菌分离株中更为常见，可能区分了来自其他非洲国家的 MDR-TB 的跨界传播。
