Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci.

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of hospital-acquired infections.
• VREfm encounters chlorhexidine through bathing and central venous catheters.
• Understanding VREfm's response to chlorhexidine is crucial for infection control.

Purpose of the Study:

• To investigate the molecular response of VREfm to chlorhexidine gluconate exposure.
• To identify genes and pathways affected by chlorhexidine at various concentrations.
• To explore the implications of chlorhexidine exposure on VREfm's antibiotic susceptibility.

Main Methods:

• RNA sequencing to analyze gene expression changes in VREfm after chlorhexidine exposure.
• Reporter gene assays and deletion analysis to study gene regulation.
• Antimicrobial susceptibility testing to assess the impact of chlorhexidine on VREfm's response to other antibiotics.

Main Results:

• Chlorhexidine exposure significantly upregulated genes associated with vancomycin resistance (vanHAX) and reduced daptomycin susceptibility (liaXYZ).
• VanA-type vancomycin resistance gene induction was confirmed as VanR-dependent and not strain-specific.
• Unexpectedly, sub-inhibitory chlorhexidine exposure increased VREfm susceptibility to vancomycin, suggesting altered cell wall synthesis.

Conclusions:

• Chlorhexidine exposure induces the expression of VanA-type vancomycin resistance and daptomycin nonsusceptibility genes in VREfm.
• The VanR regulatory protein is critical for chlorhexidine-induced vanHAX gene expression.
• Sub-inhibitory chlorhexidine concentrations can alter VREfm's antibiotic susceptibility profile, warranting further investigation.