Transposable elements are driving rapid adaptation of Enterococcus faecium.

Area of Science:

• Microbiology
• Genomics
• Evolutionary Biology

Background:

• Bacterial pathogens rapidly adapt to selective pressures.
• Insertion sequences (IS) are transposable elements that can influence pathogen adaptation.
• The activity and impact of IS in current clinical bacterial populations are not fully understood.

Purpose of the Study:

• To investigate the dynamics and consequences of IS activity in bacterial pathogens, particularly Enterococcus faecium.
• To quantify IS dynamics from global genomic patterns to within-host evolution.
• To understand the role of IS in the adaptation and clinical success of E. faecium.

Main Methods:

• Large-scale genomic surveys of publicly available pathogen genomes.
• Long-read sequencing of clinical isolates and longitudinal gut metagenomes.
• Analysis of IS density, structural variation, and regulatory impacts in E. faecium.

Main Results:

• Enterococcus faecium genomes exhibit the highest IS density, dominated by ISL3 elements, which have increased in clinical lineages over 30 years.
• Extensive chromosomal structural variation, linked to ISL3, was observed in bloodstream isolates.
• Within-host IS dynamics in haematopoietic cell transplantation (HCT) recipients showed ISL3 insertions creating strong promoters, enhancing fitness under folate limitation.

Conclusions:

• A recent expansion of ISL3 elements is driving rapid evolution in healthcare-associated E. faecium.
• IS-mediated changes in metabolic fitness, such as enhanced folate scavenging, contribute to E. faecium's success in critically ill patients.
• IS expansion may be a broadly relevant mechanism for pathogen evolution and adaptation in clinical settings.