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中国重庆 43 株低水平利奈唑胺耐药株的分子流行病学和机制。

Molecular Epidemiology and Mechanisms of 43 Low-Level Linezolid-Resistant Strains in Chongqing, China.

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Ann Lab Med. 2019 Jan;39(1):36-42. doi: 10.3343/alm.2019.39.1.36.

DOI:10.3343/alm.2019.39.1.36
PMID:30215228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6143467/
Abstract

BACKGROUND

strains with low-level resistance to linezolid (an oxazolidinone antibiotic) have become common. No large-scale study has examined the underlying mechanisms in linezolid-resistant (LRE) strains. We investigated these mechanisms and molecular characteristics in Chongqing, China.

METHODS

A total of 1,120 non-duplicated strains collected from August 2014 to June 2017 underwent drug susceptibility testing. LRE strains were screened for , , and mutations in the 23S rRNA and ribosomal proteins L3 and L4 by PCR amplification and sequencing. Multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for epidemiological analysis.

RESULTS

All 43 low-level LRE strains (minimum inhibitory concentration: 8-16 mg/L) harbored ; and 23S rRNA mutations were not detected. Novel mutations in the ribosomal proteins L3 and L4-one deletion (Q103del) and four substitutions (S113L, T35A, I98V, and N79D)-were identified. Novel amino acid substitutions at positions E60K, G197D, and T285P of the OptrA protein were observed. MLST revealed 20 types of LRE strains; the most common type was ST16 (32.6%). PFGE showed 14 strains of ST16 with unique banding patterns. Eight novel sequence types (ST823 to ST830) and one allele (95) were identified for the first time in China.

CONCLUSIONS

plays an important role in linezolid resistance and may serve as a marker for resistance screening. Since the L3 and L4 mutations did not simultaneously occur in the same strain, they play a negligible role in linezolid resistance. Epidemiological investigation suggested that the LRE cases were sporadic.

摘要

背景

对利奈唑胺(一种恶唑烷酮类抗生素)具有低水平耐药性的菌株已变得常见。尚未有大规模的研究来检查利奈唑胺耐药(LRE)菌株中的潜在机制。我们在中国重庆研究了这些机制和分子特征。

方法

共对 2014 年 8 月至 2017 年 6 月期间收集的 1120 个非重复菌株进行了药敏试验。通过 PCR 扩增和测序筛选 LRE 菌株中的 23S rRNA 和核糖体蛋白 L3 和 L4 的 、 和突变。采用多位点序列分型(MLST)和脉冲场凝胶电泳(PFGE)进行流行病学分析。

结果

所有 43 株低水平 LRE 株(最低抑菌浓度:8-16mg/L)均携带 ,未检测到 23S rRNA 突变。核糖体蛋白 L3 和 L4 中的新突变-一个缺失(Q103del)和四个取代(S113L、T35A、I98V 和 N79D)-被鉴定。OptrA 蛋白的 E60K、G197D 和 T285P 位置出现了新的氨基酸取代。MLST 显示 LRE 菌株有 20 种类型;最常见的类型是 ST16(32.6%)。PFGE 显示 14 株 ST16 具有独特的带型。在中国首次发现了 8 种新的序列类型(ST823 至 ST830)和一个等位基因(95)。

结论

在利奈唑胺耐药中起重要作用,可能作为耐药筛选的标志物。由于 L3 和 L4 突变未同时发生在同一菌株中,因此它们在利奈唑胺耐药中作用不大。流行病学调查表明,LRE 病例是散发性的。

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