Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides

Area of Science:

• Biomaterials Science
• Antimicrobial Research
• Polymer Chemistry

Background:

• Antibiotic resistance is a growing global health threat, necessitating novel antibacterial agents.
• Antimicrobial peptides (AMPs) show promise but face challenges in development.
• Facially amphiphilic structures are key to AMP efficacy and resistance suppression.

Purpose of the Study:

• To create a novel antibacterial agent using bile acids (BAs) as building blocks.
• To mimic the facially amphiphilic structure of AMPs for enhanced antimicrobial activity.
• To develop a cost-effective and stable antibacterial polymer to combat resistant infections.

Main Methods:

• Utilized bile acid skeletons to synthesize a main-chain cationic bile acid polymer (MCBAP) via polycondensation and quaternization.
• Investigated MCBAP's activity against Gram-positive (MRSA) and Gram-negative (E. coli) bacteria.
• Evaluated MCBAP's in vitro bactericidal stability, in vivo anti-infectious performance, and resistance development potential.

Main Results:

• The optimal MCBAP demonstrated potent activity against MRSA and E. coli with rapid killing efficacy.
• MCBAP exhibited superior in vitro bactericidal stability and effective in vivo anti-infectious performance in a MRSA wound model.
• MCBAP showed a low potential for developing drug resistance after repeated exposure, attributed to its macromolecular facial amphiphilicity.

Conclusions:

• Bile acids are promising building blocks for creating facially amphiphilic polymers mimicking AMPs.
• MCBAP offers a cost-effective, easily synthesized alternative for treating MRSA infections.
• This approach holds therapeutic potential for combating antibiotic resistance and MRSA infections.