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挪威首例耐万古霉素粪肠球菌VanE型分离株——表型和分子特征

The first vanE-type vancomycin resistant Enterococcus faecalis isolates in Norway - phenotypic and molecular characteristics.

作者信息

Al Rubaye Mushtaq, Janice Jessin, Bjørnholt Jørgen Vildershøj, Löhr Iren H, Sundsfjord Arnfinn, Hegstad Kristin

机构信息

Research group for Host-Microbe Interactions, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.

Research group for Host-Microbe Interactions, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.

出版信息

J Glob Antimicrob Resist. 2024 Mar;36:193-199. doi: 10.1016/j.jgar.2023.12.021. Epub 2023 Dec 27.

Abstract

OBJECTIVES

We aimed to characterize the vanE cluster and its genetic support in the first Norwegian vanE-type isolates and assess genetic relatedness to other vanE isolates.

METHODS

Two vanE-type vancomycin resistant Enterococcus faecalis (vanE-VREfs) isolates (E1 and E2) recovered from the same patient 30 months apart were examined for antimicrobial susceptibility, genome sequence, vancomycin resistance induction, vanE transferability, genome mutation rate, and phylogenetic relationship to E. faecalis closed genomes and two vanE-VREfs from North America.

RESULTS

The ST34 E1 and E2 strains expressed low-level vancomycin resistance and susceptibility to teicoplanin. Their vanE gene clusters were part of a non-transferable Tn6202. The histidine kinase part of vanS was expressed although a premature stop codon (E1) and insertion of a transposase (E2) truncated their vanS gene. The vancomycin resistance phenotype in E1 was inducible while constitutive in E2. E1 showed a 125-fold higher mutation rate than E2. Variant calling showed 60 variants but nearly identical chromosomal gene content and synteny between the isolates. Their genomes also showed high similarity to another ST34 vanE-VREfs from Canada.

CONCLUSION

In-depth genomic analyses of the first two vanE-VREfs found in Europe identified a single chromosomal insertion site of two variants of vanE-conferring Tn6202. Single nucleotide polymorphism (SNP) and core genome multilocus sequence type (cgMLST) analyses show the genomes are different. This can be explained by the high mutation rate of E1 and acquisition of different mobile genetic elements; thus, we believe the two isolates from the same patient are genetically related. Genome similarities also suggest relatedness between the Canadian and Norwegian vanE-VREfs.

摘要

目的

我们旨在对挪威首批vanE型分离株中的vanE基因簇及其遗传支持进行表征,并评估其与其他vanE分离株的遗传相关性。

方法

对从同一患者体内相隔30个月分离出的两株vanE型耐万古霉素粪肠球菌(vanE-VREfs)分离株(E1和E2)进行抗菌药敏试验、基因组测序、万古霉素耐药性诱导试验、vanE可转移性试验、基因组突变率检测,以及与粪肠球菌封闭基因组和来自北美的两株vanE-VREfs的系统发育关系分析。

结果

ST34型的E1和E2菌株表现出低水平的万古霉素耐药性和对替考拉宁的敏感性。它们的vanE基因簇是不可转移的Tn6202的一部分。尽管存在提前终止密码子(E1)和转座酶插入(E2)导致vanS基因截短,但vanS的组氨酸激酶部分仍有表达。E1中的万古霉素耐药表型是可诱导的,而E2中是组成型的。E1的突变率比E2高125倍。变异检测显示有60个变异,但分离株之间的染色体基因含量和同线性几乎相同。它们的基因组与来自加拿大的另一株ST34 vanE-VREfs也显示出高度相似性。

结论

对在欧洲发现的首批两株vanE-VREfs进行的深入基因组分析确定了携带vanE的Tn6202的两个变体的单一染色体插入位点。单核苷酸多态性(SNP)和核心基因组多位点序列类型(cgMLST)分析表明基因组存在差异。这可以通过E1的高突变率和获得不同的移动遗传元件来解释;因此,我们认为来自同一患者的这两株分离株具有遗传相关性。基因组相似性也表明加拿大和挪威的vanE-VREfs之间存在相关性。

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