Li Qiong, Tian Peng, Xu Chao, Peng Zhangli, Xu Peng, Zhang Hong, Chen Ling
Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 563003, China.
School of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou Province, 563000, China.
J Infect Chemother. 2024 Mar;30(3):208-212. doi: 10.1016/j.jiac.2023.10.006. Epub 2023 Nov 25.
As an infectious disease, tuberculosis (TB) poses a serious threat to public health. Although amikacin (AMK) is an important antibiotic for the treatment of drug-resistant TB, its resistance mechanisms are not fully understood.
To investigate the role of Rv3737 gene on AMK drug susceptibility, a Mycobacterium tuberculosis (M.tb) Rv3737 knockout strain (H37Rv△Rv3737) and a Mycobacterium smegmatis (M.sm) Rv3737 overexpressing strain (Msm/pMV261-Rv3737) were used to detect their minimal inhibitory concentrations (MICs) in this study.
The AMK MICs of Rv3737 knockout and overexpressing strains were 4-fold lower and 2-fold higher than those of the wild-type and empty plasmid strains, respectively. The results of clinical isolates showed that no Rv3737 gene mutation was found to be associated with AMK susceptibility, while the rrs A1401G mutation remained the main mechanism of high level of AMK resistance (MIC>32 μg/ml). There was a positive correlation between Rv3737 mRNA expression level and AMK MIC. In the isolates with low-level AMK resistance (MIC = 4 μg/ml) without rrs A1401G mutation, the expression level of Rv3737 gene was significantly higher than those of susceptible isolates.
In this study, the Rv3737 gene was reported for the first time for its effect on AMK susceptibility in M.tb. Although the rrs A1401G mutation remains the main reason of high-level AMK resistance, high expression of the Rv3737 gene was associated with low-level AMK resistance in clinical isolates.
作为一种传染病，结核病对公众健康构成严重威胁。尽管阿米卡星（AMK）是治疗耐药结核病的重要抗生素，但其耐药机制尚未完全明确。
为研究Rv3737基因对AMK药敏性的作用，本研究使用结核分枝杆菌（M.tb）Rv3737基因敲除菌株（H37Rv△Rv3737）和耻垢分枝杆菌（M.sm）Rv3737过表达菌株（Msm/pMV261-Rv3737）检测其最低抑菌浓度（MIC）。
Rv3737基因敲除和过表达菌株的AMK MIC分别比野生型和空质粒菌株低4倍和高2倍。临床分离株结果显示，未发现Rv3737基因突变与AMK药敏性相关，而rrs A1401G突变仍是高水平AMK耐药（MIC>32μg/ml）的主要机制。Rv3737 mRNA表达水平与AMK MIC呈正相关。在无rrs A1401G突变的低水平AMK耐药（MIC = 4μg/ml）分离株中，Rv3737基因表达水平显著高于敏感分离株。
本研究首次报道了Rv3737基因对结核分枝杆菌AMK药敏性的影响。尽管rrs A1401G突变仍是高水平AMK耐药的主要原因，但Rv3737基因的高表达与临床分离株的低水平AMK耐药相关。
