A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii

Area of Science:

• Microbiology
• Biochemistry
• Pharmacology

Background:

• Pseudomonas aeruginosa and Acinetobacter baumannii are WHO-priority pathogens.
• Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics.
• Developing novel AMPs is crucial for combating antibiotic resistance.

Purpose of the Study:

• To evaluate the antimicrobial activity and therapeutic potential of a novel α-helical antimicrobial peptide, S24.
• To investigate the mechanism of action of S24 against pathogenic bacteria.
• To assess the efficacy of S24 in a preclinical wound infection model.

Main Methods:

• Screening of α-helical AMPs using a novel multiple-descriptor strategy.
• Assessment of S24's antimicrobial activity against major pathogenic bacteria.
• Evaluation of S24's haemolytic activity, serum stability, and salt resistance.
• Investigation of S24's mechanism of action, including effects on outer membrane permeability and DNA binding.
• Testing S24's wound healing efficacy in a mouse model infected with P. aeruginosa and A. baumannii.

Main Results:

• S24 demonstrated potent antimicrobial activity against key pathogenic bacteria.
• S24 exhibited minimal haemolysis, good serum stability, and maintained salt resistance.
• The mechanism of action involves disruption of outer membrane permeability and inhibition of genomic DNA migration.
• S24 significantly promoted wound healing in a mouse model of P. aeruginosa and A. baumannii infection.

Conclusions:

• S24 displays excellent antimicrobial activity and stability under physiological conditions.
• S24's dual action on bacterial membranes and DNA contributes to its efficacy.
• S24 shows significant potential as a therapeutic agent for treating serious bacterial infections, including wound infections.