Restoring vancomycin activity against resistant Enterococcus faecalis using a transcription factor decoy as a vanA operon-inhibitor.

This article focuses on the development and evaluation of a transcription factor decoy (TFD) system targeting the vanA operon to inhibit vancomycin resistance in Enterococcus faecalis. The vanA operon encodes proteins responsible for acquired vancomycin resistance by altering cell wall precursors, reducing vancomycin binding. The study synthesized a TFD mimicking the VanR transcription factor binding site, loaded it onto cationic liposomes (TFD-lipoplexes), and demonstrated that these complexes significantly reduced vanA gene expression and lowered vancomycin minimum inhibitory concentrations (MIC) in resistant strains without affecting bacterial growth or causing cytotoxicity or hemolysis. In a systemic mouse infection model, co-administration of TFD-lipoplexes with vancomycin effectively eradicated vancomycin-resistant E. faecalis infection, restoring antibiotic efficacy in vivo. This approach offers a novel, gene-targeted therapeutic strategy against vancomycin-resistant enterococci and may be applicable to other resistance genes.