Abstract
We have studied the antimicrobial and hemolytic activity of synthetic antimicrobial peptides (SAMPs), i.e., Arg9Phe2 (P1-Arg), Lys9Phe2 (P2-Lys), and His9Phe2 (P3-His), which have a “linear” type of amphipathicity and contain the cationic amino acid residues of arginine, lysine, or histidine. In this study, we have used various pathogenic microorganism strains of gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica), gram-positive bacteria (Staphylococcus aureus), and the conditionally pathogenic yeast fungus (Candida albicans). It has been shown that the replacement of the arginine residues by lysine or histidine residues in the tested SAMPs significantly degrades their antibacterial properties in the series: P1-Arg > P2-Lys $$ \gg $$P3-His. The cationic analog of SAMP, P1-Arg, has the highest antibacterial activity (MIC50 = 43–76 μM), while peptide P3-His does not exhibit this activity (MIC50 > 100 μM). The P1-Arg and P2-Lys peptides were 6–10 times more active against the opportunistic fungus C. albicans (MIC50 6.7 and 10.9 μM, respectively) and the P3-His peptide has 100-times increased antimycotic activity (MIC50 0.6 μM) compared with their effect on bacterial cells. All of the tested peptides with the linear type of amphipathicity and low hydrophobicity, i.e., P1-Arg, P2-Lys, and P3-His, that contain only two Phe residues regardless of the presence of cationic amino acids (Arg, Lys, or His) exhibit a relatively low hemolytic activity (not more than 4% hemolysis at 1000 μM peptide concentration). Thus, considering the same synthesis efficiency (56–63%) and approximately the same low toxicity of the tested SAMPs with a linear type of amphipathicity, it is recommended to use those that contain the cationic arginine or histidine residues to create antibacterial or antifungal peptide agents, respectively.
Interaction of synthetic antimicrobial peptides of the Hylin a1 family with models of eukaryotic structures: Zwitterionic membranes and DNA
