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Replicative selfish genetic elements are driving rapid pathogenic adaptation of Enterococcus faecium
Matthew P Grieshop1,2,3, Aaron A Behr4, Sierra Bowden1
1Department of Genetics, Stanford University, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|March 31, 2025
Summary
Insertion sequences (IS) drive rapid genomic evolution in healthcare pathogens like Enterococcus faecium. The ISL3 family actively replicates, causing structural variation and enhancing gene expression for improved survival in clinical settings.
Area of Science:
- Microbiology
- Genomics
- Evolutionary Biology
Background:
- Healthcare-associated pathogens pose a significant burden.
- Understanding pathogen adaptation is crucial for control strategies.
Purpose of the Study:
- Investigate insertion sequences (IS) as mediators of rapid genomic evolution in healthcare pathogens.
- Determine the role of ISL3 family elements in Enterococcus faecium adaptation.
Main Methods:
- Analysis of 28,207 public pathogen genomes.
- Long-read sequencing of 282 Enterococcus faecium clinical isolates.
- Long-read sequencing of 28 longitudinal stool samples from hematopoietic cell transplant patients.
- Genomic and transcriptomic analysis of ISL3 activity and its regulatory effects.
Main Results:
- High copy numbers of replicative ISL3 family found in E. faecium, Streptococcus pneumoniae, and Staphylococcus aureus.
- ISL3 proliferation has increased in E. faecium over the last 30 years.
- Extensive structural variation in E. faecium genomes mediated by active ISL3 elements.
- ISL3 replication and movement observed within clinical timescales in the gut microbiome.
- ISL3 insertion enhanced folT gene expression, improving folate scavenging in E. faecium.
Conclusions:
- ISL3 expansion is a dominant driver of rapid genomic evolution in healthcare-associated E. faecium.
- Active ISL3 replication contributes to E. faecium's metabolic fitness and adaptation in clinical environments.
- This genomic plasticity influences the evolutionary trajectory of E. faecium in healthcare settings.
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