Marine-derived Peptides As Anti-biofilm and Anti-virulence Agents: Mechanistic Insights and Applications Against Microbial Pathogens.

The global surge in antibiotic resistance and chronic biofilm-related infections has heightened interest in natural peptides. Marine ecosystems harbor a wide array of biologically and structurally diverse peptides with antibiofilm and antivirulence potential. These marine-derived antimicrobial peptides (AMPs) possess unique physicochemical properties—amphipathicity, cationic charge, and conformational flexibility—that interact with the membranes and signaling systems of microorganisms. Mechanistically, these peptides interfere with quorum-sensing pathways, suppress exopolysaccharide synthesis, and downregulate genes responsible for adhesion, motility, and toxin production. Some peptides also degrade pre-formed biofilms by degrading the extracellular matrix with enzymes or by impairing cell-to-cell communication. Other peptides show immunomodulatory effects, strengthening the host’s defenses and reducing inflammation induced by infections. Recent omics-based and computational methodologies have enhanced the understanding of peptide–target interactions, enabling the rational design and optimization of peptide analogs with improved stability and selectivity. Despite challenges such as proteolytic instability, cytotoxicity, and large-scale synthesis, these biomolecules have therapeutic potential across biomedical, food, and environmental contexts. In general, understanding how marine-derived AMPs work at the molecular and mechanistic levels is a good starting point for developing effective anti-biofilm and antivirulence drugs to combat emerging microbial threats. In this review, we synthesized recent advancements in anti-virulence strategies of marine-derived AMPs. Furthermore, we conducted molecular docking against quorum-sensing regulators to identify and prioritize peptides with potential as quorum-sensing inhibitors, thereby providing mechanistic insights into their distinct anti-virulence properties. Similar content being viewed by others Data Availability No datasets were generated or analysed during the current study. Abbreviations - 5-CC: - 5-kDa Peptide Fraction from Coelomocytes - AHLs: - Acyl-Homoserine Lactones - AI-2: - Autoinducer-2 - AIPs: - Autoinducing Peptides - AMPs: - Antimicrobial Peptides - CFU: - Colony-Forming Unit - CI: - Confidence Interval - eDNA: - Extracellular DNA - EPS: - Extracellular Polymeric Substance - GAFF: - Generalized Amber Force Field - HPLC: - High-Performance Liquid Chromatography - IL: - Interleukin - LBP: - Lipopolysaccharide-Binding Protein - LC-MS: - Liquid Chromatography–Mass Spectrometry - LPS: - Lipopolysaccharides - MBC: - Minimal Bactericidal Concentration - MDR: - Multidrug-Resistant - MIC: - Minimum Inhibitory Concentration - MRSA: - Methicillin-Resistant Staphylococcus aureus - NSC: - N-Succinyl Chitosan - PSMs: - Phenol-Soluble Modulins - QS: - Quorum-Sensing - QSIs: - Quorum-Sensing Inhibitors - RiPPs: - Ribosomally Synthesized and Post-Translationally Modified Peptides - ROS: - Reactive Oxygen Species - SAR: - Structure–Activity Relationship - SEM: - Scanning Electron Microscopy - SPDBV: - Swiss-PDB Viewer - TNF-α: - Tumor Necrosis Factor-Alpha - ε-PL: - ε-Polylysine

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Colloids Surf B 169:72–81. https://doi.org/10.1016/j.colsurfb.2018.04.055 Funding This work was supported by the 2025 Global Joint Research Program funded by the Pukyong National University (202506400001), Republic of Korea. Author information Authors and Affiliations Contributions TK: Literature Search, Writing–review and editing; N.T.: Literature Search, Writing–review and editing; A.J.: Literature Search, Writing–review and editing; MIK: Writing–review & editing, Supervision, Resources; F.K.: Conceptualization, Supervising, Funding, Literature Search, Writing-review & Editing. Corresponding author Ethics declarations Ethics Approval and Consent to Participate This research paper does not contain any studies with human participants or animals. Consent for Publication Not applicable. Generative AI in scientific writing No AI technologies were utilized to write this manuscript. However, the author used the QUILBOT tool (https://quillbot.com/paraphrasing-tool) to improve the language clarity and readability. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Kim, T., Tabassum, N., Javaid, A. et al. Marine-derived Peptides As Anti-biofilm and Anti-virulence Agents: Mechanistic Insights and Applications Against Microbial Pathogens. Probiotics & Antimicro. Prot. (2026). https://doi.org/10.1007/s12602-026-10962-7 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s12602-026-10962-7