Combined action of two synthetic ultrashort antimicrobial peptides exhibiting synergistic effects against clinically significant resistant bacteria.

Abstract

Background and aim: The emergence and proliferation of multidrug-resistant bacteria pose a global health crisis. This issue arises from the overuse and misuse of antibiotics, coupled with the pharmaceutical industry's limited development of new drugs, which is constrained by financial disincentives and regulatory hurdles. This study aimed to investigate the combined antibacterial efficacy and safety profile of the combined ultrashort antimicrobial peptides (AMPs) WW-185 and WOW against antibiotic-resistant bacterial strains.

Materials and methods: The WW-185 and WOW peptides were synthesized through solid-phase methods and purified using reverse-phase high-performance liquid chromatography, and their purity was confirmed by mass spectrometry. Antibacterial activity was evaluated using broth dilution and checkerboard assays to assess both individual and combined effects of the peptides against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus [MRSA]) and Escherichia coli (including extended-spectrum beta-lactamases [ESBL]-producing strains). The synergy between the peptides was quantified using fractional inhibitory concentration indices. Hemolytic activity was also assessed to determine cytotoxicity toward red blood cells.

Results: The combination of WW-185 and WOW exerted synergistic effects against both MRSA and ESBL-producing E. coli, with reduced minimal inhibitory concentrations compared with the individual treatments. The peptides exhibited minimal hemolytic activity, indicating low toxicity.

Conclusion: The combination of the ultrashort AMPs WW-185 and WOW shows promising synergistic antibacterial effects against resistant bacteria, with potential for further therapeutic development due to their enhanced efficacy and low toxicity.