Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci

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Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci. / Sun, Lingyan; Chen, Yan; Hua, Xiaoting; Chen, Yiyi; Hong, Jinjing; Wu, Xueqing; Jiang, Yan; van Schaik, Willem; Qu, Tingting; Yu, Yunsong.

In: Journal of Antimicrobial Chemotherapy, 19.11.2019.

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Sun, Lingyan ; Chen, Yan ; Hua, Xiaoting ; Chen, Yiyi ; Hong, Jinjing ; Wu, Xueqing ; Jiang, Yan ; van Schaik, Willem ; Qu, Tingting ; Yu, Yunsong. / Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci. In: Journal of Antimicrobial Chemotherapy. 2019.

Bibtex

@article{7e431f5fe58e49de9f427911a0f8905f,
title = "Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci",
abstract = "Background: Vancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.Objectives: To determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.Methods: Fifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT-PCR.Results: Twenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.Conclusions: This study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure.",
author = "Lingyan Sun and Yan Chen and Xiaoting Hua and Yiyi Chen and Jinjing Hong and Xueqing Wu and Yan Jiang and {van Schaik}, Willem and Tingting Qu and Yunsong Yu",
year = "2019",
month = nov,
day = "19",
doi = "10.1093/jac/dkz461",
language = "English",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Tandem amplification of the vanM gene cluster drives vancomycin resistance in vancomycin-variable enterococci

AU - Sun, Lingyan

AU - Chen, Yan

AU - Hua, Xiaoting

AU - Chen, Yiyi

AU - Hong, Jinjing

AU - Wu, Xueqing

AU - Jiang, Yan

AU - van Schaik, Willem

AU - Qu, Tingting

AU - Yu, Yunsong

PY - 2019/11/19

Y1 - 2019/11/19

N2 - Background: Vancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.Objectives: To determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.Methods: Fifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT-PCR.Results: Twenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.Conclusions: This study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure.

AB - Background: Vancomycin-variable enterococci (VVE) are a potential risk factor for vancomycin resistance gene dissemination and clinical treatment failure. vanM has emerged as a new prevalent resistance determinant among clinical enterococci in China. A total of 54 vancomycin-susceptible enterococci (VSE) isolates carrying incomplete vanM gene clusters were isolated in our previous study.Objectives: To determine the potential of vanM-carrying VSE to develop vancomycin resistance and investigate the mechanism of alteration of the resistance phenotype.Methods: Fifty-four vanM-positive VSE strains were induced in vitro by culturing in increasing concentrations of vancomycin. Genetic changes between three parent VVE strains and their resistant variants were analysed using Illumina and long-read sequencing technologies, quantitative PCR and Southern blot hybridization. Changes in expression level were determined by quantitative RT-PCR.Results: Twenty-five of the 54 VSE strains carrying vanM became resistant upon vancomycin exposure. A significant increase in vanM copy number was observed ranging from 5.28 to 127.64 copies per cell in induced resistant VVE strains. The vanM transposon was identified as tandem repeats with IS1216E between them, and occurred in either the plasmid or the chromosome of resistant VVE cells. In addition, an increase in vanM expression was observed after resistance conversion in VVE.Conclusions: This study identified tandem amplification of the vanM gene cluster as a new mechanism for vancomycin resistance in VVE strains, offering a competitive advantage for VVE under antibiotic pressure.

U2 - 10.1093/jac/dkz461

DO - 10.1093/jac/dkz461

M3 - Article

C2 - 31742612

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

ER -