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隐匿性耐万古霉素的ST117呈现高度突变的操纵子。

Occult Vancomycin-Resistant ST117 Displaying a Highly Mutated Operon.

作者信息

Santona Antonella, Taviani Elisa, Fiamma Maura, Deligios Massimo, Hoang Hoa M, Sanna Silvana, Rubino Salvatore, Paglietti Bianca

机构信息

Department of Biomedical Science, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy.

Dipartimento di Scienze della Terra, Dell'ambiente e della Vita-DISTAV-Università degli Studi di Genova, Corso Europa 26, 16132 Genova, Italy.

出版信息

Antibiotics (Basel). 2023 Feb 27;12(3):476. doi: 10.3390/antibiotics12030476.

Abstract

Rare information is available on clinical encountered in Sardinia, Italy. This study investigated the antimicrobial susceptibility profiles and genotypic characteristics of isolated at the University Hospital of Sassari, Italy, using the Vitek2 system and PCR, MLST, or WGS. Vitek2 revealed two VanB-type vancomycin-resistant (VREfm) isolates (MICs mg/L = 8 and ≥32) but failed to detect vancomycin resistance in one isolate (MIC mg/L ≤ 1) despite positive genotypic confirmation of gene, which proved to be vancomycin resistant by additional phenotypic methods (MICs mg/L = 8). This isolate was able to increase its vancomycin MIC after exposure to vancomycin, unlike the "classic" occult -carrying , becoming detectable by Vitek 2 (MICs mg/L ≥ 32). All three had highly mutated operons, as part of a chromosomally integrated Tn transposon, with common missense mutations in VanH and VanB resistance proteins and specific missense mutations in the VanW accessory protein. There were additional missense mutations in VanS, VanH, and VanB proteins in the -carrying VREfm isolates compared to Vitek2. The molecular typing revealed a polyclonal hospital-associated population from Clade A1, and that -VREfm, and nearly half of vancomycin-susceptible (VSEfm) analyzed, belonged to ST117. Based on core genome-MLST, ST117 strains had different clonal types (CT), excluding nosocomial transmission of specific CT. Detecting -carrying VREfm isolates by Vitek2 may be problematic, and alternative methods are needed to prevent therapeutic failure and spread.

摘要

关于意大利撒丁岛临床中遇到的情况,相关信息较少。本研究使用Vitek2系统以及PCR、多位点序列分型(MLST)或全基因组测序(WGS),调查了意大利萨萨里大学医院分离出的菌株的抗菌药物敏感性谱和基因型特征。Vitek2检测出两株VanB型耐万古霉素肠球菌(VREfm)分离株(最低抑菌浓度[MIC]mg/L分别为8和≥32),但尽管对基因进行了阳性基因型确认,仍有一株分离株(MIC mg/L≤1)未检测到万古霉素耐药性,通过其他表型方法证实该菌株对万古霉素耐药(MIC mg/L = 8)。与“经典”携带隐匿的菌株不同,该分离株在接触万古霉素后能够提高其万古霉素MIC,从而可被Vitek 2检测到(MICs mg/L≥32)。所有三株菌株都有高度突变的操纵子,作为染色体整合的Tn转座子的一部分,VanH和VanB耐药蛋白中有常见的错义突变,VanW辅助蛋白中有特定的错义突变。与Vitek2相比,携带的VREfm分离株中VanS、VanH和VanB蛋白还有额外的错义突变。分子分型显示,医院相关菌株群体为A1分支的多克隆群体,携带的VREfm以及近一半分析的万古霉素敏感肠球菌(VSEfm)属于ST117。基于核心基因组MLST,ST117菌株有不同的克隆类型(CT),排除了特定CT的医院内传播。通过Vitek2检测携带的VREfm分离株可能存在问题,需要采用替代方法来防止治疗失败和传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f98f/10044008/1b9745e319c5/antibiotics-12-00476-g001.jpg

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