folP1和folP2基因在磺胺甲恶唑和甲氧苄啶抗分枝杆菌作用中的作用
Role of folP1 and folP2 Genes in the Action of Sulfamethoxazole and Trimethoprim Against Mycobacteria.
作者信息
Liu Tianzhou, Wang Bangxing, Guo Jintao, Zhou Yang, Julius Mugweru, Njire Moses, Cao Yuanyuan, Wu Tian, Liu Zhiyong, Wang Changwei, Xu Yong, Zhang Tianyu
机构信息
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, P.R. China.
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
出版信息
J Microbiol Biotechnol. 2015 Sep;25(9):1559-67. doi: 10.4014/jmb.1503.03053.
The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) has been shown to be active against Mycobacterium tuberculosis (Mtb) in clinical tuberculosis (TB) treatment. However, the mechanism of action of TMP-SMX against Mtb is still unknown. To unravel this, we have studied the effect of TMP and SMX by deleting the folP2 gene in Mycobacterium smegmatis (Msm), and overexpressing the Mtb and Msm folP1/2 genes in Msm. Knocking out of the folP2 gene in Msm reduced the minimum inhibitory concentration of SMX 8-fold compared with wild type. Overexpression of the folP1 genes from Mtb and Msm increased the MICs by 4- and 2-fold in Msm for SMX and TMP, respectively. We show a strong correlation between the expression of folP1 and folP2 genes and TMP-SMX resistance in mycobacteria. This suggests that a combination of FolP2 inhibitor and SMX could be used for TB treatment with a better outcome.
甲氧苄啶（TMP）和磺胺甲恶唑（SMX）联合用药在临床结核病（TB）治疗中已显示出对结核分枝杆菌（Mtb）有活性。然而，TMP-SMX对Mtb的作用机制仍不清楚。为了阐明这一点，我们通过敲除耻垢分枝杆菌（Msm）中的folP2基因，并在Msm中过表达Mtb和Msm的folP1/2基因，研究了TMP和SMX的作用效果。与野生型相比，敲除Msm中的folP2基因使SMX的最低抑菌浓度降低了8倍。来自Mtb和Msm的folP1基因的过表达分别使Msm中SMX和TMP的最低抑菌浓度提高了4倍和2倍。我们发现folP1和folP2基因的表达与分枝杆菌对TMP-SMX的耐药性之间存在很强的相关性。这表明FolP2抑制剂和SMX联合使用可用于结核病治疗，可能会取得更好的疗效。
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