Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain

Ross S. Mcinnes, Ann E. Snaith, Steven J. Dunn, Maria Papangeli, Katherine J. Hardy, Abid Hussain, Willem Van Schaik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

During the genomic characterisation of Enterococcus faecium strains (n = 39) collected in a haematology ward, we identified an isolate (OI25), which contained vanA-type vancomycin resistance genes but was phenotypically susceptible to vancomycin. OI25 could revert to resistance when cultured in the presence of vancomycin and was thus considered to be vancomycin-variable. Long-read sequencing was used to identify structural variations within the vancomycin resistance region of OI25 and to uncover its resistance reversion mechanism. We found that OI25 has a reduced ability to positively regulate expression of the vanHAX genes in the presence of vancomycin, which was associated with the insertion of an IS6-family element within the promoter region and the first 50 bp of the vanR gene. The vancomycin-resistant revertant isolates constitutively expressed vanHAX genes at levels up to 36,000-fold greater than OI25 via co-transcription with a ribosomal RNA operon. The vancomycin-resistant revertants did not exhibit a significant growth defect. During VRE outbreaks, attention should be paid to contemporaneous vancomycin-susceptible strains as these may carry silent vancomycin resistance genes that can be activated through genomic rearrangements.
Original languageEnglish
Article number2
Journalnpj Antimicrobials and Resistance
Volume2
Issue number1
DOIs
Publication statusPublished - 16 Jan 2024

Bibliographical note

Acknowledgements
We would like to thank the laboratory staff at UKHSA for the collection of the E. faecium isolates and MicrobesNG for genome sequencing of E. faecium isolates. This study was funded by a JPIAMR grant (MR/W031191/1) and a Wolfson Research Merit Award (WM160092) to W.v.S.. R.S.M., A.E.S., and M.P. were funded by the Wellcome Trust Antimicrobials and Antimicrobial Resistance Doctoral Training Programme (215154/Z/18/Z).

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