Efficacy of antimicrobial peptide combinations against antibiotic-resistant bacteria

BACKGROUND: Antimicrobial peptides are considered a promising strategy for the development of combinations effective against antibiotic-resistant bacteria. AIM: This work aimed to investigate the potential for enhancing the antibacterial activity of synthetic analogs of natural peptides and expanding their spectrum when used in combination with conventional antibiotics, antiseptics, and silver nanoparticles. METHODS: Antimicrobial activity was determined using the serial dilution in a liquid nutrient medium containing microorganisms, whereas the nature of combined action was assessed using serial dilutions by the checkerboard method. A hemolysis assay was used to evaluate the toxicity of the tested substances. RESULTS: The most frequent synergistic effects were identified for combinations of peptides PG-1, ChBac3.4, and PR-39 with AgNP-A1, AgNP-A2, and poviargol; RC, MC, and RFR ChBac3.4-1-NH2 with the antibiotics amikacin, gentamicin, and erythromycin; and PG-1, ChBac3.4, and RFR ChBac3.4(1–14) with the antiseptics amidopropyl betaine and chlorhexidine against antibiotic-resistant bacteria. The hemolysis assay demonstrated the safety of the tested combinations at concentrations substantially exceeding antimicrobial levels. CONCLUSION: The data confirm the high potential of the combined use of antimicrobial peptides, antibiotics, silver nanoparticles, and antiseptics to enhance antibacterial activity, supporting further development and clinical implementation of preparations based on PG-1 and PR-39, MC and PR-39, and RFR Bac3.4(1–14) and Bac5(20–43) for the treatment of wound infections.