la9b03752_si_001.pdf (1.3 MB)
Lasalocid Acid Antibiotic at a Membrane Surface Probed by Sum Frequency Generation Spectroscopy
journal contribution
posted on 2020-03-20, 12:37 authored by Thaddeus
W. Golbek, Lars Schmüser, Mette H. Rasmussen, Thomas B. Poulsen, Tobias WeidnerCarboxyl
polyether ionophores (CPIs) are widely used as veterinary
antibiotics and to increase food utilization in ruminating animals.
Furthermore, CPIs can target drug-resistant bacteria, but detailed
knowledge about their mode-of-action is needed to develop agents with
a reasonable therapeutic index. It has been suggested that ionophores
bind to membranes and incur large structural changes to shield a bound
ion from the hydrophobic environment of the lipid bilayer for transport.
One crucial piece of information is missing, however: Is it necessary
for the free ionophore to adsorb on the membrane surface before interacting
with a cation to facilitate cross-membrane ion transport? To answer
this question, we applied sum-frequency generation (SFG) vibrational
spectroscopy and surface tensiometry to identify the interaction between
the prototypical CPI lasalocid acid (LA) and a model membrane. Observed
changes in the surface pressure demonstrate that the free LA undergoes
a self-assembly process with the lipid monolayer. Spectra taken from
the lipid monolayer show that the free acid inserts partially into
the lipid monolayer and then after complexation with sodium chloride
disrupts the lipid monolayer. Overall, this study strongly suggests
that this must be the crucial step of LA and metal ion complexation
that allows the ionophore to traverse a lipid membrane.