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Anti-virulent Disruption of Pathogenic Biofilms using Engineered Quorum-quenching Lactonases

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Published on: January 1, 2016

On-Demand Activatable and Integrated Bioorthogonal Nanocatalyst against Biofilm-Associated Infections.

Yue Sun^1,2, Huisi Zhao^1,2, Fang Pu^1,2

¹State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

Advanced Healthcare Materials

|May 16, 2024

Summary

This study introduces an activatable bioorthogonal system for combating bacterial biofilms. The system uses a shielded catalyst activated by bacterial enzymes and pH to synthesize antibacterial agents in situ, promoting targeted infection treatment.

Keywords:

antibiofilm therapy bioorthogonal chemistry drug synthesis integrated nanocatalyst on‐demand activation

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Area of Science:

Bioorthogonal Chemistry
Antimicrobial Strategies
Catalysis

Background:

Bioorthogonal chemistry offers precise biological manipulation but faces challenges in spatial control and on-demand synthesis.
Current methods struggle with targeted delivery and activation within complex biological environments like biofilms.

Purpose of the Study:

To develop an activatable bioorthogonal system for combating biofilm-associated infections.
To enable on-demand catalytic synthesis of antibacterial molecules within bacterial biofilms.
To enhance the efficacy of antimicrobial strategies through localized drug synthesis and biofilm disruption.

Main Methods:

Constructed an integrated system with a shielded catalyst and prodrug molecules.
Engineered catalyst activation triggered by bacterial hyaluronidase (HAase) and acidic biofilm pH.
Incorporated reactive oxygen species (ROS) generation for biofilm dispersal.

Main Results:

Achieved in situ bioorthogonal catalytic synthesis of antibacterial molecules upon activation.
Demonstrated successful biofilm dispersal via ROS production.
Showcased enhanced penetration and elimination of bacteria within the biofilm.

Conclusions:

The developed system provides an efficient and safe approach for bioorthogonal catalyst design.
This work advances bioorthogonal chemistry-mediated strategies for treating biofilm infections.
Highlights the potential for localized drug synthesis in tackling challenging microbial communities.