Key Laboratory of Development and Evaluation of the Chemical and Herbal Drugs for Animal Use, Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
J Antimicrob Chemother. 2011 Sep;66(9):1983-6. doi: 10.1093/jac/dkr268. Epub 2011 Jun 23.
To study mutations at positions A2058, A2503 and U2504 (Escherichia coli numbering) of 23S rRNA and their relationship to resistance to antibiotics that target the large ribosomal subunit.
Single and dual mutations at positions 2058, 2503 and 2504 of 23S rRNA were introduced into a Mycobacterium smegmatis strain with a single functional rRNA operon. MICs of macrolide, pleuromutilin, phenicol, lincosamide and oxazolidinone antibiotics were determined for the engineered mutants. The doubling times of the mutant strains were measured to investigate how the introduced mutations affected growth rate.
Single mutations A2058G, A2503U and U2504G and double mutations A2058G-A2503U and A2058G-U2504G were successfully introduced. The A2058G mutation resulted in various levels of resistance to macrolides and clindamycin. The A2503U and U2504G mutations conferred resistance to valnemulin, chloramphenicol, florfenicol and linezolid. In addition, the A2503U mutant showed reduced susceptibility to the 16-membered macrolides tylosin, spiramycin and josamycin, and the U2504G mutant exhibited decreased susceptibility to spiramycin and josamycin. Moreover, the dual mutations A2058G-A2503U and A2058G-U2504G had co-effects on resistance to 16-membered macrolides.
23S rRNA mutations A2058G, A2503U and U2504G play key roles in resistance to clinically useful antibiotics that target the large ribosomal subunit. Furthermore, the double mutations A2058G-A2503U and A2058G-U2504G have combined effects on resistance to 16-membered macrolides.
研究 23S rRNA 中位置 A2058、A2503 和 U2504（大肠杆菌编号）的突变及其与针对大亚基的抗生素耐药性的关系。
在具有单个功能 rRNA 操纵子的分枝杆菌中引入 23S rRNA 中位置 2058、2503 和 2504 的单突变和双突变。测定了工程突变株对大环内酯类、截短侧耳素、氯霉素、林可酰胺和恶唑烷酮类抗生素的 MIC。测量突变株的倍增时间，以研究引入的突变如何影响生长速度。
成功引入了单突变 A2058G、A2503U 和 U2504G 以及双突变 A2058G-A2503U 和 A2058G-U2504G。A2058G 突变导致对大环内酯类和克林霉素的不同程度耐药。A2503U 和 U2504G 突变赋予对沃尼妙林、氯霉素、氟苯尼考和利奈唑胺的耐药性。此外，A2503U 突变株对 16 元大环内酯类药物泰乐菌素、螺旋霉素和交沙霉素的敏感性降低，而 U2504G 突变株对螺旋霉素和交沙霉素的敏感性降低。此外，双突变 A2058G-A2503U 和 A2058G-U2504G 对 16 元大环内酯类药物的耐药性具有协同作用。
23S rRNA 突变 A2058G、A2503U 和 U2504G 在耐药性方面发挥关键作用，对临床有用的针对大亚基的抗生素具有耐药性。此外，双突变 A2058G-A2503U 和 A2058G-U2504G 对 16 元大环内酯类药物的耐药性具有协同作用。
