Ikonomidis Alexandros, Grapsa Anastasia, Pavlioglou Charikleia, Demiri Antonia, Batarli Alexandra, Panopoulou Maria
a Laboratory of Microbiology, School of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
J Chemother. 2016 Dec;28(6):465-468. doi: 10.1080/1120009X.2015.1119373. Epub 2016 Feb 10.
Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.
对56株表皮葡萄球菌临床分离株进行了研究，这些分离株表现出对利奈唑胺的高水平耐药性，并在重症患者中引起菌血症。所有分离株均属于ST22克隆，在编码23SrRNA的基因中携带T2504A和C2534T突变，以及L3蛋白中的C189A、G208A、C209T和G384C错义突变，这些突变导致了Asp159Tyr、Gly152Asp和Leu94Val替代。在编码核糖体蛋白L3和L22的基因中也检测到了其他沉默突变。对这些错义突变的计算机模拟分析表明，尽管L3蛋白保留了二级基序的序列，但三级结构受到了影响。观察到的L3蛋白折叠变化为L3编码基因突变在高水平利奈唑胺耐药性中的假定作用提供了线索。此外，在利奈唑胺使用率高的医疗环境中，利奈唑胺压力可能导致选择具有L3突变的耐药突变体，这些突变体可能赋予高水平的利奈唑胺耐药性。
