An Ocellatin 4-Derived Analog with Enhanced Antibacterial Activity against Multidrug-Resistant Bacteria Promotes Neutrophil Migration and Phagocytosis

The increasing prevalence of antibiotic resistance has intensified the search for new antibacterial agents. Amphibian-derived peptides are promising candidates because of their antimicrobial activity. This study evaluated the antibacterial activity, toxicity, and effects on neutrophil function of an Ocellatin 4-derived peptide and rationally designed analogs incorporating limited sequence modifications. One analog exhibited minimum inhibitory concentrations (MICs) of 2 µM against four multidrug-resistant bacterial strains, including Acinetobacter baumannii, KPC-producing Klebsiella pneumoniae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The parent peptide had MICs ≥64 µM against these strains. No toxicity toward the human erythrocytes tested was detected at 2 µM, and the analog had an IC₅₀ of 27 µM in HaCaT keratinocytes. In the fish embryo acute toxicity (FET) test, no toxic effects were observed at 2 µM, although toxicity occurred at higher concentrations. The analog also promoted neutrophil migration and enhanced phagocytosis, with no detectable reduction in neutrophil viability under the conditions tested. These findings identify an amphibian-derived peptide analog with improved antibacterial activity and effects on neutrophil functions that holds substantial promise as a novel antibacterial agent. Further studies are needed to elucidate its mechanism of action, characterize its toxicity profile, and evaluate its antibacterial efficacy in vivo.

CNPq, CAPES, FAPDF, FINEP and FUB-UnB