LAUSR

BACKGROUND Antibiotic-resistant is considered one of the critical health challenges in the management of infectious diseases. Resistant bacterial strains to the different types of antibacterial agents have been spread worldwide. Anti-microbial peptides (AMPs), also called host defense peptides, have a broad spectrum of activity and targeting even to multi-drug resistant (MDR) bacteria, therefore, extensively studied, and developed as novel therapeutic antibacterial agents. OBJECTIVES To design a novel SK4 hybrid peptide with improved characteristics compared with the BMAP-27 and Cecropin-A natural parents' peptides. METHODS The bioinformatic analysis of the SK4 peptide in comparison with the parents BMAP-27 and Cecropin-A peptides was conducted and it was fully characterized using specialized software. The antimicrobial and the antibiofilm activity of SK4 was tested, followed by a synergistic study with five conventional antibiotics (Levofloxacin, Rifampicin, Chloramphenicol, Doxycycline, and Ampicillin). Finally, the cytotoxicity against horse erythrocytes and mammalian cells was assessed. RESULTS The SK4 peptide demonstrated broad-spectrum antimicrobial activity against both gram-positive and gram-negative bacteria. The peptide also did not show any hemolytic activity even when used at concentrations ten folds higher than its MICs value. The SK4 peptide also showed a synergistic mode of action when combined with antibiotics that resulted in a significant decrease in MIC values for both the peptide and the antibiotics. CONCLUSIONS The SK4 peptide showed better activity, selectivity, and safety profile than the parent peptides, making it a novel potential treatment for MDR bacterial infections.