Characteristics and Potential of KSL, KSL-W, and Dadapin-1 Antimicrobial Peptides for Preventing Infections of Orthopedic Prosthetic Devices: Identifying the Most Robust Candidate

Antimicrobial peptides (AMPs) are increasingly emerging as alternatives to conventional antibiotics. This study compared the antibacterial activity of two decapeptides, KSL and KSL-W, and a 23-residue peptide, Dadapin-1, against bacterial species that colonize orthopedic implants, with the aim of identifying the most effective peptide for future AMP-based anti-infective orthopedic biomaterials. <i>Staphylococcus aureus</i> ATCC 25923 was the reference strain. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm inhibitory concentration (MBIC) of the AMPs were determined in both undiluted and diluted Mueller-Hinton Broth II (MHB II) to gain a simplified perspective on the potential interference of bioenvironments. The MBICs of the AMPs were close to their MICs. In diluted broth, a concentration of 3.91 μg/mL of KSL or KSL-W was bactericidal against staphylococci and prevented biofilm formation. An eight-fold higher concentration of Dadapin-1 was required to achieve bactericidal activity. Undiluted MHB II significantly hindered the antibacterial activity of KSL and Dadapin-1, while KSL-W was notably less affected. The values of LoA, a newly developed indicator of loss of activity, confirmed these findings. Bacterial species and strain influenced LoA. Furthermore, KSL-W exhibited a protective effect on osteoblasts co-cultured with <i>S. aureus</i> ATCC 25923. Overall, KSL-W emerged as the most promising candidate for AMP-based anti-infective orthopedic biomaterials.