posted on 2022-12-28, 14:04authored byChu Wang, Yong-Hao Ma, Xiaofeng Han, Xiaolin Lu
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 α-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 β-folding-like aggregates
after interacting with the charged lipids, along with the subsequent
descending α-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.