Monomeric and Dimeric Lactoferricin B Derivatives as Potent Agents against Multidrug-Resistant Clinical Isolates of Staphylococcus aureus

Staphylococcus aureus is exhibiting an increase in antimicrobial resistance, which represents a global challenge to public health and requires the urgent development of new therapies, with synthetic peptides being a viable and novel alternative. In this investigation, high-purity monomeric and dimeric synthetic peptides derived from bovine lactoferricin were produced. These antimicrobial peptides did not affect human erythrocytes, nor did they have antagonistic effects with vancomycin and oxacillin. Bacteria treated with sublethal peptide concentrations for a long time did not develop tolerance to the evaluated peptides. The results demonstrated that dimeric peptides are more potent than their monomeric analogs, particularly peptide (RRWQWR-Nal-KKLG)2-K-Ahx, which stood out as the most promising candidate, displaying an MIC of 15 μM in both the reference strain and clinical isolates resistant to penicillin, erythromycin, tetracycline, and MRSA. SEM analysis indicated that the antibacterial activity of the peptide may cause disruption of the cell wall and/or cytoplasmic membrane and loss of intracellular contents. We concluded that the dimeric peptides evaluated showed potent and selective effects in Staphylococcus aureus strains, suggesting that these molecules could be considered as candidates for evaluation as possible therapeutic tools for combating infections caused by S. aureus.