Re-Examining Interaction between Antimicrobial Peptide Aurein 1.2 and Model Cell Membranes via SFG

Aurein 1.2 (Aur), a highly efficient 13-residue antimicrobial peptide (AMP) with a broad-spectrum antibiotic activity originally derived from the Australian frog skin secretions, can nonspecifically disrupt bacterial membranes. To deeply understand the molecular-level detail of the antimicrobial mechanism, here, we artificially established comparative experimental models to investigate the interfacial interaction process between Aur and negatively charged model cell membranes via sum frequency generation vibrational spectroscopy. Sequencing the vibrational signals of phenyl, C-H, and amide groups from Aur has characteristically helped us differentiate between the initial adsorption and subsequent insertion steps upon mutual interaction between Aur and the charged lipids. The phenyl group at the terminal phenylalanine residue can act as an anchor in the adsorption process. The time-dependent signal intensity of alpha-helices showed a sharp rise once the Aur molecules came into contact with the negatively charged lipids, indicating that the adsorption process was ongoing. Insertion of Aur into the charged lipids then offered the detectable interfacial C-H signals from Aur. The achiral and chiral amide I signals suggest that Aur had formed beta-folding-like aggregates after interacting with the charged lipids, along with the subsequent descending alpha-helical amide I signals. The above mentioned experimental results provide the molecular-level detail on how the Aur molecules interact with the cell membranes, and such a mechanism study can offer the necessary support for the AMP design and later application.

Automated summary

A highly efficient antimicrobial peptide called Aur, derived from Australian frog skin secretions, can disrupt bacterial membranes and interact with negatively charged model cell membranes. This study provides molecular-level details on the interaction between Aur and cell membranes, offering support for the design and application of antimicrobial peptides.