Antimicrobial Activity of Anuran Peptide Analogs

Amphibian venom and toxin samples are a rich source of bioactive peptides, many of which exhibit antibiotic activity. This is particularly relevant as bacterial resistance to traditional antibiotics continues to rise. In this study, we investigated the antibiotic potential of a selected amphibian-derived peptide and its analogs, modified with small alterations using rational design to enhance overall activity. One of the analogs demonstrated significant improvement, showing antibiotic activity against both Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis) at MIC values of 4 μM and 2 μM, respectively, and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) at 2 μM for all strains tested. MIC values for the original peptide varied: 32 μM (S. aureus), μM (S. epidermidis), 16 μM (E. coli), and 4 μM (K. pneumoniae). Further testing with multi-drug-resistant bacteria (Acinetobacter baumannii, Klebsiella pneumoniae carbapenemase, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus) revealed that the original peptide showed little to no activity (≥64 μM), while the analog exhibited potent activity at 2 μM for all four bacterial strains. Additionally, this analog demonstrated activity against B16F10 cancer cells and showed no toxicity to normal blood cells at the effective concentration. The peptides were also tested to evaluate their effect on neutrophil migration, and the previously mentioned peptide demonstrated the ability to induce this process. The results demonstrate that amphibian-derived peptides, particularly analogs with targeted modifications, have significant potential as antibiotic agents. Further studies are required to explore the full therapeutic potential and mechanism of action of these analogs.