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

Semeraro, Enrico F.; Marx, Lisa; Mandl, Johannes; Letofsky-Papst, Ilse; Mayrhofer, Claudia; Frewein, Moritz PK; Scott, Haden L.; Prévost, Sylvain; Bergler, Helmut; Lohner, Karl; Pabst, Georg

doi:10.7554/elife.72850

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

Journal Article · 07 June 2022 · eLife

DOI: https://doi.org/10.7554/elife.72850 · OSTI ID:2471386

^[1]; Marx, Lisa ^[1]; Mandl, Johannes ^[1]; Letofsky-Papst, Ilse ^[2]; Mayrhofer, Claudia ^[3];

^[4]; Scott, Haden L. ^[5];

^[6];

^[1]; Lohner, Karl ^[1];

^[1]

Univ. of Graz (Austria); BioTechMed Graz (Austria)
Graz University of Technology (Austria)
Center for Electron Microscopy, Graz (Austria)
Univ. of Graz (Austria); BioTechMed Graz (Austria); Inst. Laue-Langevin (ILL), Grenoble (France)
Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Inst. Laue-Langevin (ILL), Grenoble (France)

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.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; Austrian Science Fund (FWF)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2471386

Journal Information:: eLife, Journal Name: eLife Vol. 11; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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

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