[Knockout of ribosomal genes bS22 and bL37 increases the sensitivity of mycobacteria to antibiotics].
[Knockout of ribosomal genes bS22 and bL37 increases the sensitivity of mycobacteria to antibiotics].
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DOI：
10.13345/j.cjb.210480
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Chan Shan;Q. Yue;Xiaoming Ding
中科院分区：
文献类型：
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作者：
Chan Shan;Q. Yue;Xiaoming Ding
近年来，利用冷冻电镜技术在分枝杆菌核糖体中发现了两种新的蛋白。蛋白质bS22位于30S亚基的解码中心附近，蛋白质bL37位于50S亚基的肽基转移酶中心附近。由于这两种蛋白与抗生素靶向核糖体的保守区域结合，推测它们可能会影响相关药物与这些靶点的结合。因此，我们通过同源重组敲除野生型耻毛分枝杆菌mc2155中编码这两个蛋白的基因，然后测定这些突变体的生长曲线及其对相关抗生素的敏感性。结果表明，与野生型菌株相比，这两个突变体的生长速率没有显著变化。然而，突变体ΔbS22对卷曲霉素、卡那霉素、阿米卡星、链霉素、庆大霉素、帕罗霉素和湿霉素B的敏感性增加，而突变体ΔbL37对利奈唑胺的敏感性增加。这些抗生素敏感性的变化通过基因互补得以恢复。本研究提示了利用核糖体蛋白bS22和bL37作为药物设计靶点的可能性。
In recent years, two novel proteins in the ribosomes of mycobacteria have been discovered by cryo-electron microscopy. The protein bS22 is located near the decoding center of the 30S subunit, and the protein bL37 is located near the peptidyl transferase center of the 50S subunit. Since these two proteins bind to conserved regions of the ribosome targeted by antibiotics, it is speculated that they might affect the binding of related drugs to these targets. Therefore, we knocked out the genes encoding these two proteins in wild-type Mycolicibacterium smegmatis mc2155 through homologous recombination, and then determined the growth curves of these mutants and their sensitivity to related antibiotics. The results showed that compared with the wild-type strain, the growth rate of these two mutants did not change significantly. However, mutant ΔbS22 showed increased sensitivity to capreomycin, kanamycin, amikacin, streptomycin, gentamicin, paromomycin, and hygromycin B, while mutant ΔbL37 showed increased sensitivity to linezolid. These changes in antibiotics sensitivity were restored by gene complementation. This study hints at the possibility of using ribosomal proteins bS22 and bL37 as targets for drug design.