A Type I Restriction-Modification System Associated with Enterococcus faecium Subspecies Separation

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Enterococcus faecium is a major cause of hospital-acquired infections.
• Multidrug-resistant (MDR) E. faecium poses significant treatment challenges.
• E. faecium exists in distinct clades (A and B), with MDR isolates in clade A.

Purpose of the Study:

• To investigate the role of endogenous barriers in E. faecium clade separation.
• To determine if restriction-modification (R-M) systems contribute to reduced gene exchange between clades.
• To characterize R-M systems in representative E. faecium strains from different clades.

Main Methods:

• Bioinformatics analysis of E. faecium genomes.
• Deep-sequencing (second and third generation) to characterize methylomes.
• Comparative analysis of R-M systems in clade A1 and clade B isolates.

Main Results:

• A type I R-M system was identified as specific to clade A1 E. faecium.
• This R-M system is active for DNA methylation.
• The R-M system significantly reduced the transformability (horizontal gene transfer) of clade A1 isolates.

Conclusions:

• R-M systems function as barriers to horizontal gene exchange in E. faecium.
• R-M systems contribute to the phylogenetic separation observed between E. faecium clades.
• This provides a mechanism for the distinct evolutionary trajectories of E. faecium clades, particularly the hospital-epidemic clade.