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

TL;DR

This study explores the antibacterial potential of dermaseptin peptide derivatives against drug-resistant bacteria, showing they are effective and less toxic than traditional antibiotics.

Contribution

The study introduces modified dermaseptin peptides with improved antibacterial activity and reduced cytotoxicity against MDR bacteria.

Findings

Dermaseptin S4 derivatives showed higher antibacterial activity than B2 derivatives against both bacteria strains.

All tested analogs had MICs between 6.25 to 25 μg/mL and MBCs between 12.5 to 50 μg/mL.

Modifying peptides with additional positive charges enhanced their activity and reduced toxicity.

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: Klebsiella pneumonia and Staphyloccus epidermidis 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 Staphylococcus epidermis and Klebsiella pneumoniae. 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 Staphylococcus epidermis and Klebsiella pneumoniae. 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 Klebsiella pneumoniae and Staphylococcus epidermidis.

•S4 are more active than B2: at low doses in μg/ml against both bacteria strains.•All analogs antibacterial activity with (MICs 6.25 to 25 μg/mL ; MBCs 12.5 to 50 μg/mL).•The cytotoxicity of DRSs was concentration-dependent at microgram concentrations.•Increasing positive charges via mono- or bi-substitution improves biological activity and reduces cytotoxicity.

S4 are more active than B2: at low doses in μg/ml against both bacteria strains.

All analogs antibacterial activity with (MICs 6.25 to 25 μg/mL ; MBCs 12.5 to 50 μg/mL).

The cytotoxicity of DRSs was concentration-dependent at microgram concentrations.

Increasing positive charges via mono- or bi-substitution improves biological activity and reduces cytotoxicity.

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