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Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability

Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, ra...

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Autores principales: Snoussi, Mehdi, Talledo, John Paul, Del Rosario, Nathan-Alexander, Mohammadi, Salimeh, Ha, Bae-Yeun, Košmrlj, Andrej, Taheri-Araghi, Sattar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298785/
https://www.ncbi.nlm.nih.gov/pubmed/30560784
http://dx.doi.org/10.7554/eLife.38174
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author Snoussi, Mehdi
Talledo, John Paul
Del Rosario, Nathan-Alexander
Mohammadi, Salimeh
Ha, Bae-Yeun
Košmrlj, Andrej
Taheri-Araghi, Sattar
author_facet Snoussi, Mehdi
Talledo, John Paul
Del Rosario, Nathan-Alexander
Mohammadi, Salimeh
Ha, Bae-Yeun
Košmrlj, Andrej
Taheri-Araghi, Sattar
author_sort Snoussi, Mehdi
collection PubMed
description Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, rapid absorption and retention of a large number of LL37 peptides by E. coli cells upon the inhibition of their growth, which increases population survivability. This transition occurs more likely in the late stage of cell division cycles. Cultures with high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising observations, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37 peptides.
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spelling pubmed-62987852018-12-25 Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability Snoussi, Mehdi Talledo, John Paul Del Rosario, Nathan-Alexander Mohammadi, Salimeh Ha, Bae-Yeun Košmrlj, Andrej Taheri-Araghi, Sattar eLife Computational and Systems Biology Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, rapid absorption and retention of a large number of LL37 peptides by E. coli cells upon the inhibition of their growth, which increases population survivability. This transition occurs more likely in the late stage of cell division cycles. Cultures with high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising observations, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37 peptides. eLife Sciences Publications, Ltd 2018-12-18 /pmc/articles/PMC6298785/ /pubmed/30560784 http://dx.doi.org/10.7554/eLife.38174 Text en © 2018, Snoussi et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Snoussi, Mehdi
Talledo, John Paul
Del Rosario, Nathan-Alexander
Mohammadi, Salimeh
Ha, Bae-Yeun
Košmrlj, Andrej
Taheri-Araghi, Sattar
Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title_full Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title_fullStr Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title_full_unstemmed Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title_short Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
title_sort heterogeneous absorption of antimicrobial peptide ll37 in escherichia coli cells enhances population survivability
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298785/
https://www.ncbi.nlm.nih.gov/pubmed/30560784
http://dx.doi.org/10.7554/eLife.38174
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