University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
Lisa Marx
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
Johannes Mandl
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
Ilse Letofsky-Papst
Institute of Electron Microscopy and Nanoanalysis and Center for Electron Microscopy, Graz University of Technology, NAWI Graz, Graz, Austria
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria; Institut Laue-Langevin, Grenoble, France
Haden L Scott
Center for Environmental Biotechnology, University of Tennessee, Knoxville, United States; Shull Wollan Center, Oak Ridge National Laboratory, Oak Ridge, United States
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
Karl Lohner
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
University of Graz, Institute of Molecular Biosciences, NAWI Graz, Graz, Austria; BioTechMed Graz, Graz, Austria; Field of Excellence BioHealth – University of Graz, Graz, Austria
We report the real-time response of Escherichia coli to lactoferricin-derived antimicrobial peptides (AMPs) on length scales bridging microscopic cell sizes to nanoscopic lipid packing using millisecond time-resolved synchrotron small-angle X-ray scattering. Coupling a multiscale scattering data analysis to biophysical assays for peptide partitioning revealed that the AMPs rapidly permeabilize the cytosolic membrane within less than 3 s—much faster than previously considered. Final intracellular AMP concentrations of ∼80–100 mM suggest an efficient obstruction of physiologically important processes as the primary cause of bacterial killing. On the other hand, damage of the cell envelope and leakage occurred also at sublethal peptide concentrations, thus emerging as a collateral effect of AMP activity that does not kill the bacteria. This implies that the impairment of the membrane barrier is a necessary but not sufficient condition for microbial killing by lactoferricins. The most efficient AMP studied exceeds others in both speed of permeabilizing membranes and lowest intracellular peptide concentration needed to inhibit bacterial growth.