Bacteriophage-derived depolymerases as antimicrobial synergists: A strategy to overcome resistance
Shuhong Han1,2,3, David H Yang4, Jiayin Shen1,2,3
1National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
Bioscience Trends
|February 8, 2026
Summary
Bacterial polysaccharide barriers like CPS, EPS, and LPS fuel antimicrobial resistance. Depolymerases, evolved by bacteriophages, degrade these barriers, enhancing antibiotic and phage therapy efficacy.
Area of Science:
- Microbiology
- Biotechnology
- Drug Discovery
Background:
- Bacteria utilize polysaccharide layers (CPS, EPS, LPS) as protective barriers.
- These barriers impede antibiotic diffusion and host immune responses, contributing to antimicrobial resistance.
- Bacteriophages possess depolymerase enzymes that degrade bacterial polysaccharide structures.
Purpose of the Study:
- To review the therapeutic potential of depolymerases as adjuncts to existing antimicrobial strategies.
- To evaluate depolymerases' ability to enhance antibiotic efficacy and phage therapy.
- To explore evolutionary dynamics and clinical translation challenges of depolymerase-based treatments.
Main Methods:
- Systematic literature review of depolymerase functions and applications.
- Analysis of depolymerase mechanisms in degrading bacterial polysaccharides.
- Integration of evolutionary biology principles to predict resistance development.
Main Results:
- Depolymerases show significant promise in enhancing antibiotic penetration and effectiveness.
- Phage therapy efficacy can be improved by co-administering depolymerases.
- Understanding bacterial adaptive responses to depolymerases is crucial for sustained therapeutic success.
Conclusions:
- Depolymerases represent a valuable synergistic approach to combatting antimicrobial resistance.
- Further research into formulation and clinical application is needed for depolymerase translation.
- Depolymerase-based therapies offer a promising avenue to overcome bacterial defense mechanisms.
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