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Published on: December 23, 2022
Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium
Sarah L Baines1, Romain Guérillot1, Susan Ballard2
1Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Abstract:
Vancomycin-resistant Enterococcus (VRE) is an increasingly identified cause of human disease, with most infections resulting from the vanA and vanB genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a vanD VRE faecium (VREfm), which arose de novo during a single infectious episode. The genomes of the vancomycin-susceptible E. faecium (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole-genome alignments, cross-mapping and orthologue clustering used to identify genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6 kb integrative conjugative element (ICE) harbouring the vanD locus. (ii) The native ligase (ddl) was disrupted by an ISEfm1 insertion. (iii) A large 1.74 Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of vanD-harbouring genomes identified strong similarities in the 120-160 kb genomic region surrounding vanD, suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographical and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of vanD VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.
Insights
A novel vanD vancomycin-resistant Enterococcus faecium (VREfm) emerged from a susceptible strain via acquisition of a mobile genetic element carrying the vanD gene. This element is globally disseminated and can transfer between bacterial genera, highlighting a potential spread mechanism for antimicrobial resistance.
Area of Science:
- Microbiology
- Genomics
- Antimicrobial Resistance
Background:
- Vancomycin-resistant Enterococcus (VRE) is a significant cause of human infections, primarily due to vanA and vanB genotypes.
- Limited knowledge exists regarding the emergence and spread of other VRE genotypes, such as vanD.
Purpose of the Study:
- To genomically characterize the emergence of vanD VRE faecium (VREfm) from a vancomycin-susceptible E. faecium (VSEfm) strain.
- To investigate the genomic variations and mobile genetic elements involved in the VREfm development.
- To compare the vanD VREfm with global vanD-harboring isolates to understand dissemination patterns.
Main Methods:
- Long-read whole-genome sequencing and genome closure of VSEfm and VREfm isolates.
- Whole-genome alignments, cross-mapping, and orthologue clustering to identify genomic differences.
- Phylogenetic analysis and comparison with a global collection of vanD-harboring Enterococcus genomes.
Main Results:
- The VREfm acquired a 142.6 kb integrative conjugative element (ICE) containing the vanD locus.
- The native ligase gene (ddl) was disrupted by an IS Efm1 insertion.
- A large 1.74 Mb chromosomal inversion occurred in the VREfm.
- Genomic comparisons revealed a conserved region around the vanD locus, suggesting a common mobile element and integration site across diverse isolates.
- Evidence indicates the putative ICE is globally disseminated and transferable across different bacterial genera.
Conclusions:
- The vanD VREfm arose de novo through the acquisition of a globally disseminated integrative conjugative element.
- This ICE facilitates the spread of vanD resistance and can be acquired by various bacterial genera.
- Understanding the emergence and spread of vanD VREfm is critical for combating antimicrobial resistance.
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