Shan Chan, Yue Qianwen, Ding Xiaoming
School of Life Sciences, Fudan University, Shanghai 200433, China.
Sheng Wu Gong Cheng Xue Bao. 2022 Mar 25;38(3):1061-1073. doi: 10.13345/j.cjb.210480.
In recent years, two novel proteins in the ribosomes of 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 mc155 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 Δ showed increased sensitivity to capreomycin, kanamycin, amikacin, streptomycin, gentamicin, paromomycin, and hygromycin B, while mutant Δ 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.
近年来，通过冷冻电子显微镜在[具体生物名称]的核糖体中发现了两种新蛋白质。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。由于这两种蛋白质与抗生素靶向的核糖体保守区域结合，推测它们可能会影响相关药物与这些靶点的结合。因此，我们通过同源重组在野生型[具体生物名称]mc155中敲除了编码这两种蛋白质的基因，然后测定了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，这两种突变体的生长速率没有显著变化。然而，突变体Δ对卷曲霉素、卡那霉素、阿米卡星、链霉素、庆大霉素、巴龙霉素和潮霉素B的敏感性增加，而突变体Δ对利奈唑胺的敏感性增加。通过基因互补恢复了这些抗生素敏感性的变化。这项研究暗示了将核糖体蛋白bS22和bL37用作药物设计靶点的可能性。
