Lactoferricins impair the cytosolic membrane of Escherichia coli within a few seconds and accumulate inside the cell
- University of Graz, Austria
- Graz University of Technology, Austria
- Institut Laue-Langevin, France
- University of Tennessee at Knoxville, United States
Abstract
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.
Data availability
The current manuscript is a biophysical study, reporting data analysis of scattering data and peptide partitioning assays in vitro. All relevant data are included and plotted in the manuscript.In addition SANS raw data are accessible (DOI in Methods and Materials section).The modelling code for data analysis consists of a standard chi-squared minimization algorithm. The implemented analytical functions are described in the Methods and Materials section of the manuscript.
Article and author information
Author details
Enrico Federico Semeraro
Funding
Austrian Science Fund (P 30921)
- Karl Lohner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Patricia Bassereau, Institut Curie, France
Version history
- Received: August 6, 2021
- Preprint posted: September 26, 2021 (view preprint)
- Accepted: June 6, 2022
- Accepted Manuscript published: June 7, 2022 (version 1)
- Version of Record published: August 4, 2022 (version 2)
Copyright
© 2022, Semeraro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Lactoferricins impair the cytosolic membrane of Escherichia coli within a few seconds and accumulate inside the cell
eLife 11:e72850.
https://doi.org/10.7554/eLife.72850
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