Programmable Peptide Nanofibers Enable Effective MRSA Biofilm Eradication and Infection Control

Area of Science:

• Biochemistry
• Microbiology
• Materials Science

Background:

• Rising antibiotic resistance necessitates novel therapeutic strategies.
• Antimicrobial peptides (AMPs) offer broad-spectrum activity against pathogens.
• Methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging due to biofilm formation.

Purpose of the Study:

• To engineer tryptophan-arginine-rich antimicrobial peptides targeting S. aureus.
• To investigate the self-assembly and antibacterial properties of designed peptides.
• To evaluate peptide efficacy against planktonic and biofilm MRSA.

Main Methods:

• Peptide engineering and synthesis (D6W, D6W1R, D6W2R).
• Structural analysis (conformations, self-assembly into nanofibers).
• Antibacterial assays against planktonic and biofilm MRSA.
• Molecular dynamics simulations.
• Ex vivo and in vivo efficacy studies.
• Mammalian cell toxicity assessments.

Main Results:

• Engineered peptides self-assemble into fibrillar or oligomeric structures.
• D6W2R demonstrated the highest antibacterial activity against S. aureus.
• Peptide nanofibers effectively inhibited and disrupted MRSA biofilms.
• Antibacterial efficacy was maintained in ex vivo and in vivo models.
• Minimal toxicity was observed in mammalian cells.

Conclusions:

• Self-assembled antimicrobial peptides exhibit potent and selective activity against MRSA.
• These peptides are effective against both planktonic bacteria and challenging biofilms.
• The engineered peptides represent a promising therapeutic approach for MRSA infections.