Short Antimicrobial Peptides Based on Arginine and Tryptophan: Agents with Potential in Combating Resistant Pathogens

Area of Science:

• Biochemistry and Molecular Biology
• Microbiology and Infectious Diseases
• Drug Discovery and Development

Background:

• Rising antimicrobial resistance necessitates novel therapeutic strategies beyond conventional antibiotics.
• Antimicrobial peptides (AMPs) offer a promising alternative due to broad-spectrum activity and low resistance induction potential.

Purpose of the Study:

• To design, synthesize, and evaluate novel seven-residue Arg/Trp-based antimicrobial peptides.
• To assess the antimicrobial activity, mechanism of action, synergistic potential, and safety profile of these peptides.

Main Methods:

• Peptide synthesis and characterization.
• Antimicrobial activity testing against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria, including clinical isolates.
• Mechanism of action studies (SYTOX Green uptake, AFM, TEM) and synergistic/resensitization assays with existing antibiotics.
• Eukaryotic cell toxicity and C. elegans survival model studies.

Main Results:

• The peptide (WRW)2F demonstrated potent bactericidal activity against tested pathogens.
• Mechanism of action involves rapid membrane permeabilization and structural disruption, not efflux pump inhibition.
• Active peptides showed synergy with linezolid and resensitized methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin.
• Favorable safety profile observed in eukaryotic cells and C. elegans models.

Conclusions:

• Short Arg/Trp-rich peptides, particularly (WRW)2F, are effective against resistant bacterial pathogens.
• These peptides represent affordable, easily synthesized, and biocompatible candidates for enhancing antibiotic efficacy.
• Demonstrated potential for use in combination therapies to combat challenging infections.