Antimicrobial peptides against enterococcus spp. biofilms: a systematic review

Abstract

Introduction: Infections caused by Enterococcus spp. remain a clinical challenge due to intrinsic antimicrobial resistance and strong biofilm-forming capacity. The increasing prevalence of vancomycin-resistant enterococci further restricts therapeutic options, reinforcing the need for alternative strategies such as antimicrobial peptides. Methods: This systematic review followed PRISMA guidelines, with its protocol registered on the OSF platform, and included studies published between 2015 and 2025 in PubMed, Web of Science, and the Virtual Health Library. Eligible studies evaluated antimicrobial peptides activity against Enterococcus biofilms through inhibition, eradication, or mechanistic analyses. Data were extracted on peptide characteristics, cytotoxicity, mechanisms of action, and therapeutic applications, and risk of bias was assessed using a ten-item checklist for in vitro studies. Results: Most studies focused on E. faecalis using in vitro models. Antimicrobial peptides demonstrated consistent ability to inhibit biofilm formation and reduce biomass of mature structures. Reported mechanisms included membrane permeabilization, extracellular matrix disruption, interference with adhesion pathways, and modulation of metabolic and intracellular processes. Cationic amphipathic peptides showed the strongest preventive effects, while engineered analogs, lipopeptides, and enzyme-linked peptides enhanced antibiofilm potency. Synergy with antibiotics or adjunctive therapies was frequently observed. However, methodological variability and limited physiologically relevant models restrict translational potential. Conclusion: Overall, antimicrobial peptides represent a promising therapeutic platform, but standardized methodologies and robust in vivo studies are essential for clinical application.