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Journal article
Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number
International journal of antimicrobial agents, Vol.62(1), 106849
2023
PMID: 37187337
Abstract
Vancomycin variable enterococci (VVE) are van-positive enterococci with a vancomycin-susceptible phenotype (VVE-S) that can convert to a resistant phenotype (VVE-R) and be selected for during vancomycin exposure. VVE-R outbreaks have been reported in Canada and Scandinavian countries. The aim of this study was to examine the presence of VVE in whole genome sequenced (WGS) Australian bacteremia Enterococcus faecium (Efm) isolates collected through the Australian Group on Antimicrobial resistance (AGAR) network. Eight potential VVEAus isolates, all identified as Efm ST1421, were selected based on the presence of vanA and a vancomycin-susceptible phenotype. During vancomycin selection, two potential VVE-S harboring intact vanHAX genes, but lacking the prototypic vanRS and vanZ genes, reverted to a resistant phenotype (VVEAus-R). Spontaneous VVEAus-R reversion occurred at a frequency of 4-6 × 10−8 resistant colonies per parent cell in vitro after 48 h and led to high-level vancomycin and teicoplanin resistance. The S to R reversion was associated with a 44-bp deletion in the vanHAX promoter region and an increased vanA plasmid copy number. The deletion in the vanHAX promoter region enables an alternative constitutive promoter for the expression of vanHAX. Acquisition of vancomycin resistance was associated with a low fitness cost compared with the corresponding VVEAus-S isolate. The relative proportion of VVEAus-R vs. VVEAus-S decreased over time in serial passages without vancomycin selection. Efm ST1421 is one of the predominant VanA-Efm multilocus sequence types found across most regions of Australia, and has also been associated with a major prolonged VVE outbreak in Danish hospitals.
Details
- Title
- Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number
- Authors/Creators
- Theresa Maria Wagner - UiT The Arctic University of NorwayJessin Janice - UiT The Arctic University of NorwayMark Schulz - The University of MelbourneSusan A Ballard - The University of MelbourneAnders Goncalves da Silva - The University of MelbourneGeoffrey W Coombs - Antimicrobial Resistance and Infectious Disease (AMRID) Research Laboratory, Murdoch University, Murdoch, Western Australia, AustraliaDenise A Daley - Fiona Stanley HospitalStanley Pang - Murdoch UniversityShakeel Mowlaboccus - Murdoch UniversityTim Stinear - The University of MelbourneKristin Hegstad - UiT The Arctic University of NorwayBenjamin P Howden - The University of MelbourneArnfinn Sundsfjord - UiT The Arctic University of Norway
- Publication Details
- International journal of antimicrobial agents, Vol.62(1), 106849
- Publisher
- Elsevier Ltd
- Identifiers
- 991005579450907891
- Copyright
- Crown Copyright © 2023
- Murdoch Affiliation
- Centre for Biosecurity and One Health
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.173 MRSA and VRE
- Web Of Science research areas
- Infectious Diseases
- Microbiology
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology