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大环内酯类耐药相关基因在多药耐药株中的特征。

Characterization of Two Macrolide Resistance-Related Genes in Multidrug-Resistant Isolates.

机构信息

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.

School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China.

出版信息

Pol J Microbiol. 2020 Sep;69(3):349-356. doi: 10.33073/pjm-2020-038. Epub 2020 Sep 8.

Abstract

In analyzing the drug resistance phenotype and mechanism of resistance to macrolide antibiotics of clinical isolates, the agar dilution method was used to determine the minimum inhibitory concentrations (MICs), and PCR (polymerase chain reaction) was applied to screen for macrolide antibiotics resistance genes. The macrolide antibiotics resistance genes were cloned, and their functions were identified. Of the 13 antibiotics tested, strains showed high resistance rates (ranging from 69.5-82.1%), and MIC levels (MIC90 > 256 μg/ml) to macrolide antibiotics. Of the 131 known macrolide resistance genes, only two genes, and , were identified in 262 clinical isolates. Four strains (1.53%, 4/262) carried both the and genes, and an additional three strains (1.15%, 3/262) harbored the gene alone. The cloned and genes conferred higher resistance levels to three second-generation macrolides compared to two first-generation ones. Analysis of MsrE and MphE protein polymorphisms revealed that they are highly conserved, with only 1-3 amino acids differences between the proteins of the same type. It can be concluded that even though the strains showed high resistance levels to macrolides, known macrolide resistance genes are seldom present in clinical strains, demonstrating that a mechanism other than this warranted by the and genes may play a more critical role in the bacteria's resistance to macrolides.

摘要

在分析临床分离株对大环内酯类抗生素耐药表型和耐药机制时,采用琼脂稀释法测定最小抑菌浓度(MIC),并应用 PCR 筛选大环内酯类抗生素耐药基因。克隆大环内酯类抗生素耐药基因并鉴定其功能。在测试的 13 种抗生素中,菌株对大环内酯类抗生素表现出高耐药率(范围为 69.5-82.1%)和 MIC 水平(MIC90>256μg/ml)。在已知的 131 种大环内酯类耐药基因中,仅在 262 株临床分离株中鉴定出 2 种基因 和 。有 4 株(1.53%,4/262)携带 和 基因,另有 3 株(1.15%,3/262)携带 基因。克隆的 和 基因赋予三种第二代大环内酯类药物比两种第一代大环内酯类药物更高的耐药水平。MsrE 和 MphE 蛋白多态性分析表明,它们高度保守,同型蛋白之间仅存在 1-3 个氨基酸差异。可以得出结论,尽管菌株对大环内酯类药物表现出高耐药水平,但临床分离株中很少存在已知的大环内酯类耐药基因,这表明除了 和 基因所证明的机制外,其他机制可能在细菌对大环内酯类药物的耐药性中发挥更关键的作用。

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