Antibiotics | Marine Antimicrobial Peptides: New Hope in Combating Drug-Resistant Bacteria and Biofilm Infections

This article systematically reviews research advances in marine-derived antimicrobial peptides (AMPs) for combating multidrug-resistant bacteria and biofilm-forming pathogens. It details structural characteristics, mechanisms of action, and their potential in targeting drug-resistant bacteria, inhibiting biofilm formation, and modulating bacterial quorum-sensing systems, offering fresh perspectives on addressing the antimicrobial resistance crisis.

 

Literature Overview
This review article, 'Marine Antimicrobial Peptides: Emerging Strategies Against Multidrug-Resistant and Biofilm-Forming Bacteria', published in the journal Antibiotics, summarizes the roles of marine-derived AMPs in combating multidrug-resistant and biofilm-associated bacterial infections. It highlights how marine AMPs, with their structural diversity, broad-spectrum antimicrobial activity, and low resistance-induction risk, have emerged as promising next-generation anti-infective candidates amid stalled traditional antibiotic development and surging drug-resistant infections.

Background Knowledge
Antimicrobial resistance (AMR) has become a critical global public health threat, projected to surpass cancer-related mortality by 2050. Conventional antibiotics primarily target bacterial cell wall synthesis or protein synthesis, mechanisms easily neutralized by resistance systems. In contrast, AMPs offer multi-target antimicrobial actions through membrane disruption, biofilm interference, and QS modulation, which bacteria struggle to adapt to. The marine ecosystem, characterized by extreme environments and high biodiversity, serves as an ideal source for AMP screening, with peptides like pleurocidin, clavanins, and epinecidin-1 already demonstrating potent activity against MRSA, VRE, and biofilm-associated pathogens. Despite extensive in vitro evidence, clinical translation of marine AMPs faces challenges in stability, bioavailability, and scalable production, making structural optimization and pharmacokinetic enhancement central research priorities.

 

 

Research Methods and Experiments
This study systematically analyzed the antimicrobial activity, biofilm inhibition capacity, and effects on persister cells of marine AMPs. By integrating literature data and database statistics (e.g., APD3), it evaluated minimum inhibitory concentrations (MICs), minimum biofilm inhibitory concentrations (MBICs), and minimum bactericidal concentrations (MBCs) across various pathogens. The authors also summarized structural diversity, synthesis mechanisms, and environmental tolerance advantages of marine AMPs.

Key Conclusions and Perspectives

• Marine AMPs employ multiple mechanisms—including membrane disruption, biofilm inhibition, QS interference, and immune modulation—to effectively combat drug resistance and chronic infections.
• Several AMPs (e.g., pleurocidin, clavanin, epinecidin-1, gaduscidin-1) have demonstrated potent antimicrobial activity in vitro and animal models, particularly against MRSA, VRE, P. aeruginosa, and biofilm-associated strains.
• AMPs' resistance-induction risk is minimal due to their membrane-targeting mechanisms, requiring extensive structural mutations for bacterial adaptation—a rare event.
• Marine AMPs maintain activity under extreme conditions (high salinity, pressure, pH fluctuations), enhancing their in vivo stability.
• Despite robust preclinical evidence, no marine AMPs have reached clinical approval yet, primarily limited by low bioavailability, high production costs, and poor in vivo stability.
• Emerging technologies like nanodelivery systems, AMP-antibiotic conjugates, and structural modifications (e.g., cyclization, amidation) can enhance pharmacokinetic profiles and accelerate clinical translation.
• Future research should prioritize immunomodulatory functions, biofilm mechanism elucidation, and peptide engineering to improve therapeutic indices and safety profiles.

Research Significance and Prospects
This systematic review highlights marine AMPs' unique advantages in combating drug-resistant and biofilm-associated infections. By integrating omics technologies, bioinformatics, and machine learning, the study proposes pathways to expedite AMP discovery and structural optimization, paving the way for next-generation antimicrobial therapies.

 

 

Conclusion
As natural immune effectors, marine antimicrobial peptides demonstrate multidimensional potential against drug-resistant bacteria and biofilm infections. Their diverse mechanisms, low resistance risk, and environmental adaptability position them as strong antibiotic alternatives. While clinical translation remains challenging, innovations in delivery systems, structural modifications, and synthetic biology offer solutions to overcome these limitations. Future efforts should focus on in vivo stability, safety evaluation, and peptide engineering to realize effective antimicrobial therapies.

 

Rita Magalhães, Dalila Mil-Homens, Sónia Cruz, and Manuela Oliveira. Marine Antimicrobial Peptides: Emerging Strategies Against Multidrug-Resistant and Biofilm-Forming Bacteria. Antibiotics.