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Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells

Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to pla...

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Autores principales: Goormaghtigh, Frédéric, Fraikin, Nathan, Putrinš, Marta, Hallaert, Thibaut, Hauryliuk, Vasili, Garcia-Pino, Abel, Sjödin, Andreas, Kasvandik, Sergo, Udekwu, Klas, Tenson, Tanel, Kaldalu, Niilo, Van Melderen, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016239/
https://www.ncbi.nlm.nih.gov/pubmed/29895634
http://dx.doi.org/10.1128/mBio.00640-18
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author Goormaghtigh, Frédéric
Fraikin, Nathan
Putrinš, Marta
Hallaert, Thibaut
Hauryliuk, Vasili
Garcia-Pino, Abel
Sjödin, Andreas
Kasvandik, Sergo
Udekwu, Klas
Tenson, Tanel
Kaldalu, Niilo
Van Melderen, Laurence
author_facet Goormaghtigh, Frédéric
Fraikin, Nathan
Putrinš, Marta
Hallaert, Thibaut
Hauryliuk, Vasili
Garcia-Pino, Abel
Sjödin, Andreas
Kasvandik, Sergo
Udekwu, Klas
Tenson, Tanel
Kaldalu, Niilo
Van Melderen, Laurence
author_sort Goormaghtigh, Frédéric
collection PubMed
description Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems. Cells in which TA systems are activated are thought to enter a dormancy state and therefore survive the antibiotic treatment. Using independently constructed strains and newly designed fluorescent reporters, we reassessed the roles of TA modules in persistence both at the population and single-cell levels. Our data confirm that the deletion of 10 TA systems does not affect persistence to ofloxacin or ampicillin. Moreover, microfluidic experiments performed with a strain reporting the induction of the yefM-yoeB TA system allowed the observation of a small number of type II persister cells that resume growth after removal of ampicillin. However, we were unable to establish a correlation between high fluorescence and persistence, since the fluorescence of persister cells was comparable to that of the bulk of the population and none of the cells showing high fluorescence were able to resume growth upon removal of the antibiotic. Altogether, these data show that there is no direct link between induction of TA systems and persistence to antibiotics.
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spelling pubmed-60162392018-06-26 Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells Goormaghtigh, Frédéric Fraikin, Nathan Putrinš, Marta Hallaert, Thibaut Hauryliuk, Vasili Garcia-Pino, Abel Sjödin, Andreas Kasvandik, Sergo Udekwu, Klas Tenson, Tanel Kaldalu, Niilo Van Melderen, Laurence mBio Research Article Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems. Cells in which TA systems are activated are thought to enter a dormancy state and therefore survive the antibiotic treatment. Using independently constructed strains and newly designed fluorescent reporters, we reassessed the roles of TA modules in persistence both at the population and single-cell levels. Our data confirm that the deletion of 10 TA systems does not affect persistence to ofloxacin or ampicillin. Moreover, microfluidic experiments performed with a strain reporting the induction of the yefM-yoeB TA system allowed the observation of a small number of type II persister cells that resume growth after removal of ampicillin. However, we were unable to establish a correlation between high fluorescence and persistence, since the fluorescence of persister cells was comparable to that of the bulk of the population and none of the cells showing high fluorescence were able to resume growth upon removal of the antibiotic. Altogether, these data show that there is no direct link between induction of TA systems and persistence to antibiotics. American Society for Microbiology 2018-06-12 /pmc/articles/PMC6016239/ /pubmed/29895634 http://dx.doi.org/10.1128/mBio.00640-18 Text en Copyright © 2018 Goormaghtigh et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Goormaghtigh, Frédéric
Fraikin, Nathan
Putrinš, Marta
Hallaert, Thibaut
Hauryliuk, Vasili
Garcia-Pino, Abel
Sjödin, Andreas
Kasvandik, Sergo
Udekwu, Klas
Tenson, Tanel
Kaldalu, Niilo
Van Melderen, Laurence
Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title_full Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title_fullStr Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title_full_unstemmed Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title_short Reassessing the Role of Type II Toxin-Antitoxin Systems in Formation of Escherichia coli Type II Persister Cells
title_sort reassessing the role of type ii toxin-antitoxin systems in formation of escherichia coli type ii persister cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016239/
https://www.ncbi.nlm.nih.gov/pubmed/29895634
http://dx.doi.org/10.1128/mBio.00640-18
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