Interaction of Halictine-Related Antimicrobial Peptides with Membrane Models

• Published in: International journal of molecular sciences Vol. 20; no. 3; p. 631
• Main Authors: Pazderková, Markéta, Maloň, Petr, Zíma, Vlastimil, Hofbauerová, Kateřina, Kopecký, Jr, Vladimír, Kočišová, Eva, Pazderka, Tomáš, Čeřovský, Václav, Bednárová, Lucie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2019; MDPI
• Subjects: Amino acid sequence; Amino acids; antibacterial peptides; Antibiotics; Antimicrobial agents; Antimicrobial peptides; Bacteria; Cardiolipin; Circular dichroism; Conformation; Cytoplasmic membranes; Dichroism; Drug resistance; fluorescence; Glycerol; Gram-negative bacteria; Gram-positive bacteria; halictine; infrared spectroscopy; Lipids; Lipopolysaccharides; Membranes; Mimicry; Peptides; Peptidoglycans; Phosphatidylethanolamine; Phosphatidylglycerol; Sodium dodecyl sulfate; Spectrum analysis; circular dichroism; fluorescence; antibacterial peptides; halictine; infrared spectroscopy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20030631

We have investigated structural changes of peptides related to antimicrobial peptide Halictine-1 (HAL-1) induced by interaction with various membrane-mimicking models with the aim to identify a mechanism of the peptide mode of action and to find a correlation between changes of primary/secondary structure and biological activity. Modifications in the HAL-1 amino acid sequence at particular positions, causing an increase of amphipathicity (Arg/Lys exchange), restricted mobility (insertion of Pro) and consequent changes in antimicrobial and hemolytic activity, led to different behavior towards model membranes. Secondary structure changes induced by peptide-membrane interaction were studied by circular dichroism, infrared spectroscopy, and fluorescence spectroscopy. The experimental results were complemented by molecular dynamics calculations. An α-helical structure has been found to be necessary but not completely sufficient for the HAL-1 peptides antimicrobial action. The role of alternative conformations (such as β-sheet, PPII or 3 -helix) also seems to be important. A mechanism of the peptide mode of action probably involves formation of peptide assemblies (possibly membrane pores), which disrupt bacterial membrane and, consequently, allow membrane penetration.