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Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with...

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Autores principales: Saebelfeld, Manja, Das, Suman G., Brink, Jorn, Hagenbeek, Arno, Krug, Joachim, de Visser, J. Arjan G. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417073/
https://www.ncbi.nlm.nih.gov/pubmed/34489889
http://dx.doi.org/10.3389/fmicb.2021.698970
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author Saebelfeld, Manja
Das, Suman G.
Brink, Jorn
Hagenbeek, Arno
Krug, Joachim
de Visser, J. Arjan G. M.
author_facet Saebelfeld, Manja
Das, Suman G.
Brink, Jorn
Hagenbeek, Arno
Krug, Joachim
de Visser, J. Arjan G. M.
author_sort Saebelfeld, Manja
collection PubMed
description For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e., the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a β-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment.
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spelling pubmed-84170732021-09-05 Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants Saebelfeld, Manja Das, Suman G. Brink, Jorn Hagenbeek, Arno Krug, Joachim de Visser, J. Arjan G. M. Front Microbiol Microbiology For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing β-lactamase activity (i.e., the capacity to hydrolyze β-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a β-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant β-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment. Frontiers Media S.A. 2021-08-19 /pmc/articles/PMC8417073/ /pubmed/34489889 http://dx.doi.org/10.3389/fmicb.2021.698970 Text en Copyright © 2021 Saebelfeld, Das, Brink, Hagenbeek, Krug and de Visser. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Saebelfeld, Manja
Das, Suman G.
Brink, Jorn
Hagenbeek, Arno
Krug, Joachim
de Visser, J. Arjan G. M.
Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title_full Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title_fullStr Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title_full_unstemmed Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title_short Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants
title_sort antibiotic breakdown by susceptible bacteria enhances the establishment of β-lactam resistant mutants
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417073/
https://www.ncbi.nlm.nih.gov/pubmed/34489889
http://dx.doi.org/10.3389/fmicb.2021.698970
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