Antibacterial activity of peptide derivatives of dermaseptins against multidrug-resistant Klebsiella pneumoniae and Staphylococcus epidermis

Abstract

The emergence of infections caused by multi-drug resistant bacteria (MDR) to antibiotic treatments poses a significant challenge in the healthcare field. Indeed, the resistance of MDR such as: <i>Klebsiella pneumonia</i> and <i>Staphyloccus epidermidis</i> to antibiotics has become an increasingly concerning issue, especially in hospital settings, necessitating the development of new therapies and more potent antimicrobial agents. Although numerous conventional antibiotic agents have been developed in recent years, but many of them still present toxicity to eukaryotic cells, despite their significant efficacy against multi-resistant microorganisms. Therefore, antimicrobial peptides (AMPs), particularly, dermaseptins (DRSs), are considered promising candidates against MDR, mainly due to their low toxicity and their different mode of action compared to conventional antibiotics. Indeed, these peptides are generally less likely to lead to the resistance phenomena observed for traditional antibiotics. The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4 and B2, and to ascertain their antibacterial potency against <i>Staphylococcus epidermis</i> and <i>Klebsiella pneumoniae.</i> The dermaseptin peptide derivatives used in this study were K₄K₂₀S4, K₄S4(1-16), B2 and K₃K₄B2. In this research, we describe the synthesis and the bioactivity of DRSs and their derivatives against <i>Staphylococcus epidermis</i> and <i>Klebsiella pneumoniae</i>. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. The cytotoxicity of DRSs was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 6.25 to 25 μg/ml and Minimum Bactericidal Concentrations (MBCs) ranging from 12.5 to 50 μg/ml. In summary, these findings indicate that dermaseptins could serve as promising lead compounds for the development of potent antibacterial agents targeting infections caused by <i>Klebsiella pneumoniae</i> and <i>Staphylococcus epidermidis</i>.