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Published on: December 14, 2020
Combating Pseudomonas aeruginosa Biofilms by a Chitosan-PEG-Peptide Conjugate via Changes in Assembled Structure
Xiaoyan Ju1,2, Jun Chen3, Mengxue Zhou3
1Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) biofilms are associated with a wide range of infections, from chronic tissue diseases to implanted medical devices. In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100-1000 times tolerance of the bacteria. In view of the water-filled channels in biofilms and the highly negative charge of EPS, we design a chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) in this study. The CS-PEG-LK13 prefers a neutrally charged assembly at a size of ∼100 nm in aqueous environment, while undergoes disassembly to expose the α-helical peptide at the bacterial cell membrane. This behavior provides CS-PEG-LK13 superiorities in both penetrating the biofilms and inactivating the bacteria. At a concentration of 8 times the minimum inhibitory concentration, CS-PEG-LK13 has a much higher antibacterial efficiency (72.70%) than LK13 peptide (15.24%) and tobramycin (33.57%) in an in vitro P. aeruginosa biofilm. Moreover, CS-PEG-LK13 behaves comparable capability of combating an implanted P. aeruginosa biofilm to highly excess tobramycin. This work has implications for the design of new antibacterial agents in biofilm combating.
Insights
A novel chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) effectively penetrates Pseudomonas aeruginosa biofilms and inactivates bacteria. This new agent shows superior efficacy compared to existing treatments for biofilm infections.
Area of Science:
- Biomaterials Science
- Microbiology
- Drug Delivery
Background:
- Pseudomonas aeruginosa biofilms are linked to persistent infections and medical device failures.
- The extracellular polymeric substance (EPS) in biofilms hinders antibiotic penetration, causing significant bacterial tolerance.
- Biofilm structure presents challenges for conventional antibacterial agents.
Purpose of the Study:
- To design and evaluate a novel chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) for combating Pseudomonas aeruginosa biofilms.
- To investigate the self-assembly and disassembly properties of CS-PEG-LK13 in aqueous environments and at bacterial cell membranes.
- To assess the antibacterial efficacy of CS-PEG-LK13 against in vitro and implanted Pseudomonas aeruginosa biofilms.
Main Methods:
- Synthesis and characterization of the chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13).
- Evaluation of CS-PEG-LK13's self-assembly and disassembly behavior in response to environmental cues.
- In vitro testing of CS-PEG-LK13's efficacy against Pseudomonas aeruginosa biofilms, comparing it with LK13 peptide and tobramycin.
- In vivo assessment of CS-PEG-LK13's performance in combating implanted Pseudomonas aeruginosa biofilms.
Main Results:
- CS-PEG-LK13 forms stable ∼100 nm assemblies in aqueous solution and disassembles to expose its active peptide at bacterial membranes.
- At 8x MIC, CS-PEG-LK13 achieved 72.70% biofilm inhibition, significantly outperforming LK13 peptide (15.24%) and tobramycin (33.57%).
- CS-PEG-LK13 demonstrated comparable efficacy to high concentrations of tobramycin against implanted Pseudomonas aeruginosa biofilms.
Conclusions:
- CS-PEG-LK13 exhibits unique properties enabling effective biofilm penetration and bacterial inactivation.
- The designed conjugate offers a promising strategy for developing advanced antibacterial agents against challenging biofilm infections.
- This study provides a foundation for novel therapeutic designs targeting biofilm-associated diseases.
