Molecular mechanisms of virulence in Enterococcus faecium: integrating Esp, Acm, regulatory RNA networks in multidrug resistant nosocomial infections.

Enterococcus faecium represents a critical healthcare associated pathogen, having evolved from a commensal gut inhabitant into a leading cause of multidrug resistant nosocomial infections. Its transition to pathogenicity involves the coordinated acquisition of resistance determinants and virulence factors enabling adhesion, biofilm formation, and immune evasion. This review provides an integrated synthesis of classical virulence determinants Enterococcal surface protein (Esp) and collagen binding adhesin (Acm) with emerging molecular regulators such as small regulatory RNAs (sRNAs) and extracellular vehicles (EVs). We highlight how these RNA mediated and vesicle based systems interact with traditional surface factors to modulate virulence expression, antibiotic resistance, and hospital adaptation. By bridging these molecular networks, this review underscores a systems level understanding of E. faecium pathogenesis and explores how these mechanisms collectively drive persistence in clinical environments. Emerging therapeutic strategies targeting biofilm disruption, adhesin inhibition, phage therapy, and immunomodulation are discussed as potential interventions against this evolving pathogen.