Star-shaped polypeptides exhibit potent antibacterial activities.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Antimicrobial Research

Background:

• Peptide-based biomaterials offer a novel antimicrobial strategy by targeting bacterial cell membranes.
• This mechanism reduces the likelihood of developing drug resistance compared to intracellular targets.
• Developing effective and selective antimicrobial agents remains a critical challenge.

Purpose of the Study:

• To synthesize and evaluate cationic, star-shaped polypeptides as antimicrobial agents.
• To investigate the impact of arm number and side chain modification on antimicrobial activity.
• To assess the efficacy and safety of lead candidates in vitro and in vivo.

Main Methods:

• Synthesis of star-shaped polypeptides with varying arm numbers (3-8 arms).
• Modification of poly(l-lysine) with indole groups (PLL-g-indo).
• Antimicrobial activity testing against diverse bacterial strains.
• Cytotoxicity and hemolytic activity assays.
• In vivo efficacy studies using a mouse model of Enterohaemorrhagic E. coli (EHEC) infection.

Main Results:

• Star-shaped polypeptides exhibited enhanced antimicrobial activity compared to linear counterparts.
• Antimicrobial efficacy increased with arm number up to 8 arms.
• PLL-g-indo displayed the most potent activity and improved selectivity against pathogens over mammalian cells.
• Star-shaped PLL-g-indo effectively suppressed EHEC infection and reduced clinical symptoms in mice.

Conclusions:

• Cationic, star-shaped polypeptides are effective antimicrobial agents with reduced susceptibility to resistance.
• Indole modification and increased arm number enhance antimicrobial potency and selectivity.
• Star-shaped PLL-g-indo represents a promising candidate for treating bacterial infections, including EHEC.