Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing a deletion in vanX

Thomas Arn Hansen; Martin Schou Pedersen; Lone Gilmor Nielsen; Chih Man German Ma; Lillian Marie Søes; Peder Worning; Christian Østergaard; Henrik Westh; Mette Pinholt; Kristian Schønning

doi:10.1093/jac/dky308

Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing a deletion in vanX

Thomas Arn Hansen, Martin Schou Pedersen, Lone Gilmor Nielsen, Chih Man German Ma, Lillian Marie Søes, Peder Worning, Christian Østergaard, Henrik Westh, Mette Pinholt, Kristian Schønning^*

^*Corresponding author for this work

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

Background: Primary screening for VRE with PCR directed against vanA allowed identification of vanA! samples from which VRE could not be isolated when selective culture methods were used. From such a sample a vancomycin-susceptible, vanA! Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection was not used during culture. Similar isolates with variable susceptibility to vancomycin were obtained in the following months. Objectives: To characterize Efm-V1511 and investigate the causes of variable susceptibility to vancomycin. Methods: All strains were sequenced using Illumina technology. Plasmids containing vanA were reconstructed by scaffolding to known plasmids or plasmids were sequenced using Oxford Nanopore MinION. Derived structures were verified by PCR and sequencing. Furthermore, selected vanA! vancomycin-susceptible isolates were passaged in the presence of vancomycin and vancomycin-resistant variants obtained were sequenced. Results: Efm-V1511 belonged to ST1421 and contained a 49 696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this element vanX was truncated by a 252 bp 3⁰ deletion explaining the susceptibility of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH-V1511 were identified. All were ST1421. In isolates resistant to vancomycin, resistance could be attributed to changes in ddl disrupting gene function sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the existence of an additional vanA-containing plasmid encoding a functional vanX. Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for VRE.

Original language	English
Journal	Journal of Antimicrobial Chemotherapy
Volume	73
Issue number	11
Pages (from-to)	2936-2940
ISSN	0305-7453
DOIs	https://doi.org/10.1093/jac/dky308
Publication status	Published - 1 Nov 2018

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@article{f57efd32165d4035875ede4a270c2760,

title = "Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing a deletion in vanX",

abstract = "Background: Primary screening for VRE with PCR directed against vanA allowed identification of vanA! samples from which VRE could not be isolated when selective culture methods were used. From such a sample a vancomycin-susceptible, vanA! Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection was not used during culture. Similar isolates with variable susceptibility to vancomycin were obtained in the following months. Objectives: To characterize Efm-V1511 and investigate the causes of variable susceptibility to vancomycin. Methods: All strains were sequenced using Illumina technology. Plasmids containing vanA were reconstructed by scaffolding to known plasmids or plasmids were sequenced using Oxford Nanopore MinION. Derived structures were verified by PCR and sequencing. Furthermore, selected vanA! vancomycin-susceptible isolates were passaged in the presence of vancomycin and vancomycin-resistant variants obtained were sequenced. Results: Efm-V1511 belonged to ST1421 and contained a 49 696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this element vanX was truncated by a 252 bp 30 deletion explaining the susceptibility of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH-V1511 were identified. All were ST1421. In isolates resistant to vancomycin, resistance could be attributed to changes in ddl disrupting gene function sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the existence of an additional vanA-containing plasmid encoding a functional vanX. Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for VRE.",

author = "Hansen, {Thomas Arn} and Pedersen, {Martin Schou} and Nielsen, {Lone Gilmor} and Ma, {Chih Man German} and S{\o}es, {Lillian Marie} and Peder Worning and Christian {\O}stergaard and Henrik Westh and Mette Pinholt and Kristian Sch{\o}nning",

year = "2018",

month = nov,

day = "1",

doi = "10.1093/jac/dky308",

language = "English",

volume = "73",

pages = "2936--2940",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "11",

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TY - JOUR

T1 - Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing a deletion in vanX

AU - Hansen, Thomas Arn

AU - Pedersen, Martin Schou

AU - Nielsen, Lone Gilmor

AU - Ma, Chih Man German

AU - Søes, Lillian Marie

AU - Worning, Peder

AU - Østergaard, Christian

AU - Westh, Henrik

AU - Pinholt, Mette

AU - Schønning, Kristian

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Primary screening for VRE with PCR directed against vanA allowed identification of vanA! samples from which VRE could not be isolated when selective culture methods were used. From such a sample a vancomycin-susceptible, vanA! Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection was not used during culture. Similar isolates with variable susceptibility to vancomycin were obtained in the following months. Objectives: To characterize Efm-V1511 and investigate the causes of variable susceptibility to vancomycin. Methods: All strains were sequenced using Illumina technology. Plasmids containing vanA were reconstructed by scaffolding to known plasmids or plasmids were sequenced using Oxford Nanopore MinION. Derived structures were verified by PCR and sequencing. Furthermore, selected vanA! vancomycin-susceptible isolates were passaged in the presence of vancomycin and vancomycin-resistant variants obtained were sequenced. Results: Efm-V1511 belonged to ST1421 and contained a 49 696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this element vanX was truncated by a 252 bp 30 deletion explaining the susceptibility of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH-V1511 were identified. All were ST1421. In isolates resistant to vancomycin, resistance could be attributed to changes in ddl disrupting gene function sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the existence of an additional vanA-containing plasmid encoding a functional vanX. Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for VRE.

AB - Background: Primary screening for VRE with PCR directed against vanA allowed identification of vanA! samples from which VRE could not be isolated when selective culture methods were used. From such a sample a vancomycin-susceptible, vanA! Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection was not used during culture. Similar isolates with variable susceptibility to vancomycin were obtained in the following months. Objectives: To characterize Efm-V1511 and investigate the causes of variable susceptibility to vancomycin. Methods: All strains were sequenced using Illumina technology. Plasmids containing vanA were reconstructed by scaffolding to known plasmids or plasmids were sequenced using Oxford Nanopore MinION. Derived structures were verified by PCR and sequencing. Furthermore, selected vanA! vancomycin-susceptible isolates were passaged in the presence of vancomycin and vancomycin-resistant variants obtained were sequenced. Results: Efm-V1511 belonged to ST1421 and contained a 49 696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this element vanX was truncated by a 252 bp 30 deletion explaining the susceptibility of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH-V1511 were identified. All were ST1421. In isolates resistant to vancomycin, resistance could be attributed to changes in ddl disrupting gene function sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the existence of an additional vanA-containing plasmid encoding a functional vanX. Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for VRE.

U2 - 10.1093/jac/dky308

DO - 10.1093/jac/dky308

M3 - Journal article

C2 - 30113682

AN - SCOPUS:85055214158

SN - 0305-7453

VL - 73

SP - 2936

EP - 2940

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 11

ER -

Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing a deletion in vanX

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