Lactoferricins impair the cytosolic membrane of Escherichia coli within a few seconds and accumulate inside the cell

Enrico Federico Semeraro*, Lisa Marx, Johannes Mandl, Ilse Letofsky-Papst, Claudia Mayrhofer, Moritz P.K. Frewein, Haden L. Scott, Sylvain Prevost, Helmut Bergler, Karl Lohner, Georg Pabst*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We report the real-time response of E. 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 multi-scale scattering data analysis to biophysical assays for peptide partitioning revealed that the AMPs rapidly permeabilize the cytosolic membrane within less than three seconds-much faster than previously considered. Final intracellular AMP concentrations of ~ 80 to 100 mM suggest an efficient obstruction of physiologically important processes as primary cause for 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.
Original languageEnglish
Article numbere72850
Number of pages28
Publication statusPublished - 2022

ASJC Scopus subject areas

  • General Materials Science

Fields of Expertise

  • Advanced Materials Science

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)


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