利奈唑啉
23S核糖体RNA
粪肠球菌
微生物学
生物
放大器
最小抑制浓度
核糖体RNA
分子生物学
抗生素
遗传学
聚合酶链反应
细菌
核糖核酸
金黄色葡萄球菌
基因
万古霉素
核糖体
作者
Xinxin Shan,Bingya Liu,Zhang Long-xian,Congming Zou,Runhao Yu,Štefan Schwarz,Yanhong Shang,Dexi Li,Andrea Brenciani,Xiang‐Dang Du
摘要
Abstract Objectives This study aimed to explore the evolutionary patterns and resistance mechanisms of an Enterococcus faecalis strain harbouring poxtA under linezolid exposure. Methods A poxtA-carrying E. faecalis electrotransformant DJH702 with a linezolid minimum inhibitory concentration of 4 mg/L was exposed to increasing concentrations of linezolid (8–64 mg/L). The derived strains growing at 8, 16, 32 and 64 mg/L, designed DJH702_8, DJH702_16, DJH702_32 and DJH702_64, were obtained. The amplification and overexpression of poxtA were measured using sequencing and RT–PCR, the fitness cost by competition assays and the stability of the repeat units by serial passage. Results In all derived strains, high-level linezolid resistance develops through poxtA amplification. The relative copy numbers and transcription levels of poxtA were significantly increased. However, in the presence of higher linezolid concentrations, DJH702_32 and DJH702_64 showed reduced poxtA copy numbers and transcription levels compared with DJH702_8 and DJH702_16, but additional mutations in the 23S rRNA (G2505A). IS1216E-mediated formation of translocatable units with subsequent tandem amplification of these translocatable units supported the gain of poxtA segments. However, these amplicons were not stable and were lost frequently in the absence of a linezolid selection pressure. The amplification of the poxtA region did not result in a fitness cost, but mutations in 23S rRNA did. Conclusions poxtA-carrying E. faecalis electrotransformants used two distinct mechanisms to resist linezolid selection pressure: at lower concentrations, strains prioritized increasing poxtA expression levels, while at higher concentrations, a combination of increased poxtA expression and mutations in 23S rRNA was observed.
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