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中国新型 23S rRNA 基因 C2128T 突变致头葡萄球菌耐利奈唑胺机制研究。

Mechanisms of linezolid resistance in Staphylococcus capitis with the novel mutation C2128T in the 23S rRNA gene in China.

机构信息

The Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin, 150001, China.

Heilongjiang Longwei Precision Medical Laboratory Center, Harbin, China.

出版信息

BMC Microbiol. 2022 Aug 20;22(1):203. doi: 10.1186/s12866-022-02616-9.

Abstract

PURPOSE

The objective of this study was to investigate the molecular characteristics and potential resistance mechanisms of linezolid-resistant (LZR) Staphylococcus capitis isolates from a tertiary hospital in China.

METHODS

S. capitis isolates were obtained from clinical patient specimens; three of the isolates came from blood cultures and one from the hydrothorax. The agar dilution and E-test methods were used to identify antibiotic resistance. The chloramphenicol-florfenicol resistance (cfr) gene carrier status of the strains was determined by PCR. Whole-genome sequencing (WGS) was used to identify point mutations and L3, L4, and L22 mutations and to study the genetic environment of the cfr gene and the relationships between strains.

RESULTS

The 4 isolates obtained in this study were all linezolid-resistant Staphylococcus strains. A similar of susceptibility profile pattern was observed in all four S. capitis strains, each of which exhibited a multidrug-resistant phenotype. A potentially novel mutation, C2128T, was identified, and the cfr genes of S. capitis strains were all positive. Additionally, the same mutations (C2128T and G2600T) were identified in all 23S rRNA sequences of the isolates, whereas mutations were lacking in the L3, L4, and L22 ribosomal proteins. The genetic environments surrounding cfr were identical in all four isolates. A schematic diagram of the phylogenetic tree showed that they were closely related to AYP1020, CR01, and TW2795, and a total of seven drug resistance genes were identified in these strains.

CONCLUSIONS

The study indicated that the resistance of the Staphylococcus capitis strains to linezolid was caused by multiple mechanisms, and a potential novel mutation, C2128T, that may have an impact on bacterial resistance was identified.

摘要

目的

本研究旨在探讨中国一家三级医院耐(linezolid-resistant,LZR) 型表皮葡萄球菌分离株的分子特征和潜在耐药机制。

方法

从临床患者标本中获取表皮葡萄球菌分离株;其中 3 株来自血培养,1 株来自胸腔积液。采用琼脂稀释法和 E 试验法鉴定抗生素耐药性。采用 PCR 法检测菌株中氯霉素-氟苯尼考耐药(cfr)基因的携带状态。采用全基因组测序(WGS)技术鉴定点突变和 L3、L4 和 L22 突变,并研究 cfr 基因的遗传环境以及菌株间的关系。

结果

本研究中获得的 4 株分离株均为耐利奈唑胺的葡萄球菌株。所有 4 株表皮葡萄球菌分离株的药敏谱模式相似,均表现为多重耐药表型。鉴定出一种潜在的新型突变 C2128T,且表皮葡萄球菌分离株的 cfr 基因均呈阳性。此外,所有分离株的 23S rRNA 序列均存在相同的突变(C2128T 和 G2600T),而在 L3、L4 和 L22 核糖体蛋白中则没有突变。所有 4 株分离株的 cfr 基因周围的遗传环境均相同。系统发育树的示意图显示,它们与 AYP1020、CR01 和 TW2795 密切相关,在这些菌株中总共鉴定出 7 种耐药基因。

结论

本研究表明,表皮葡萄球菌对利奈唑胺的耐药性是由多种机制引起的,并且鉴定出一种潜在的新型突变 C2128T,该突变可能对细菌耐药性产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3fd/9392311/7e71078a535f/12866_2022_2616_Fig1_HTML.jpg

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