Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Enterococcus faecium is a common cause of hospital-acquired infections.
• Vancomycin resistance in enterococci is a significant clinical concern.
• Vancomycin-variable enterococci (VVE) represent a unique subset with potential for resistance.

Purpose of the Study:

• To investigate the occurrence and characteristics of vancomycin-variable enterococci (VVE) in a central Italian hospital.
• To understand the genetic mechanisms underlying the transition from vancomycin susceptibility to resistance in VVE.

Main Methods:

• Antibiotic susceptibility testing and molecular typing (PFGE, MLST) of VVE isolates.
• Whole Genome Sequencing (WGS) to analyze vanA gene clusters and associated genetic elements.
• Experimental assessment of resistance reversion upon vancomycin exposure and plasmid analysis using qPCR.

Main Results:

• Identified VVE-susceptible (VVE-S) isolates with two distinct vanA cluster configurations.
• Demonstrated that a subset of VVE-S strains could regain vancomycin resistance (VVE-R) via a 44-bp deletion in the vanH/vanA/vanX promoter region.
• Observed unstable resistance phenotype in revertants and increased plasmid copy number, suggesting a role in resistance expression.

Conclusions:

• VVE can transition to vancomycin-resistant enterococci (VRE) during therapy, posing a risk of treatment failure.
• Reported the first identification of VVE-S isolates with pstS-null mutation belonging to ST1478.
• Highlights the clinical importance of monitoring VVE during vancomycin treatment.