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[两株引起关节感染的菌株的抗生素分析及全基因组测序]

[Antibiotic analysis and whole genome sequencing of two strains causing joint infection].

作者信息

Wang H, Cheng F, Dong X T, Li X F, Wang Y J, Hao M J

机构信息

Department of General Surgery, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014,China.

Department of Clinical Laboratory Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2020 Dec 6;54(12):1441-1447. doi: 10.3760/cma.j.cn112150-20200922-01226.

Abstract

To analyze the molecular characteristics and antibiotic susceptibility of two strains of isolated from patients with joint infection using whole genome sequencing. Two strains of causing knee-joint infections in two elderly patients were collected in January 2020. Whole genome sequencing was used to determine the nocardia species. Drug sensitivity test was performed using the micro-broth dilution and E-test method according to CLSI M24 guideline. ABRicate was used to analyze drug resistance and virulence genes. Snippy and other bioinformatic tools were used for genomic comparison, and to construct SNP homologous tree. The clinical isolates in this study were both . Antimicrobial susceptibility test showed the isolates were resistant to ceftriaxone, cefepime, cefotaxime and trimethoprim/sulfamethoxazole (TMP/SMX). Imipenem, linezolid and amoxicillin-clavulanic acid showed good activity. Four antibiotic resistance genes including class A β-lactamase gene , RNA polymerase binding protein gene , multi-drug resistance efflux pump transcription activator gene and regulatory transcription factor gene were identified in the genomes, which conferred resistance to beta-lactams, rifampicin, macrolides and vancomycin respectively. No acquired TMP/SMX resistance genes were identified. There are multiple missense mutations in the dihydrofolate reductase family genes. Four virulence genes of and that are homologous to were found. SNP homologous tree analysis showed the two Nocardia strains were closely related, and there were only ten SNP sites, six compound substitutions and one deletion mutation between them. Whole genome sequencing technology is helpful to explore the molecular characteristics and resistance mechanisms of Nocardia species. has a trend of spreading in China. Resistance to TMP/SMX is worthy of attention. The mutation of genes involved in the metabolic pathway of dihydrofolate might be one of multiple TMP/SMX resistance mechanisms.

摘要

利用全基因组测序分析从关节感染患者中分离出的两株菌株的分子特征和抗生素敏感性。2020年1月收集了两株导致两名老年患者膝关节感染的菌株。采用全基因组测序确定诺卡菌属菌种。根据CLSI M24指南,使用微量肉汤稀释法和E-test法进行药敏试验。使用ABRicate分析耐药基因和毒力基因。使用Snippy和其他生物信息学工具进行基因组比较,并构建单核苷酸多态性(SNP)同源树。本研究中的临床分离株均为[具体菌种]。药敏试验显示分离株对头孢曲松、头孢吡肟、头孢噻肟和甲氧苄啶/磺胺甲恶唑(TMP/SMX)耐药。亚胺培南、利奈唑胺和阿莫西林-克拉维酸显示出良好的活性。在[具体菌种]基因组中鉴定出四个抗生素耐药基因,包括A类β-内酰胺酶基因[具体基因名称]、RNA聚合酶结合蛋白基因[具体基因名称]、多药耐药外排泵转录激活基因[具体基因名称]和调节转录因子基因[具体基因名称],它们分别赋予对β-内酰胺类、利福平、大环内酯类和万古霉素的耐药性。未鉴定出获得性TMP/SMX耐药基因。二氢叶酸还原酶家族基因存在多个错义突变。发现了与[相关菌种]同源的[具体菌种]的四个毒力基因。SNP同源树分析显示两株诺卡菌菌株密切相关,它们之间仅有10个SNP位点、6个复合替换和1个缺失突变。全基因组测序技术有助于探索诺卡菌属菌种的分子特征和耐药机制。[具体菌种]在中国有传播趋势。对TMP/SMX的耐药性值得关注。参与二氢叶酸代谢途径的基因的突变可能是TMP/SMX多种耐药机制之一。

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