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Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli

BACKGROUND: Bacterial persistence describes a phenomenon wherein a small subpopulation of cells is able to survive a challenge with high doses of an antibiotic (or other stressor) better than the majority of the population. Previous work has shown that cells that are in a dormant or slow-growing sta...

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Autores principales: Hofsteenge, Niels, van Nimwegen, Erik, Silander, Olin K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682893/
https://www.ncbi.nlm.nih.gov/pubmed/23379956
http://dx.doi.org/10.1186/1471-2180-13-25
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author Hofsteenge, Niels
van Nimwegen, Erik
Silander, Olin K
author_facet Hofsteenge, Niels
van Nimwegen, Erik
Silander, Olin K
author_sort Hofsteenge, Niels
collection PubMed
description BACKGROUND: Bacterial persistence describes a phenomenon wherein a small subpopulation of cells is able to survive a challenge with high doses of an antibiotic (or other stressor) better than the majority of the population. Previous work has shown that cells that are in a dormant or slow-growing state are persistent to antibiotic treatment and that populations with higher fractions of dormant cells exhibit higher levels of persistence. These data suggest that a major determinant of the fraction of persisters within a population is the rate at which cells enter and exit from dormancy. However, it is not known whether there are physiological changes in addition to dormancy that influence persistence. Here, we use quantitative measurements of persister fractions in a set of environmental isolates of E. coli together with a mathematical model of persister formation to test whether a single general physiological change, such as cell dormancy, can explain the differences in persister phenotypes observed in different strains. RESULTS: If a single physiological change (e.g. cell dormancy) underlies most persister phenotypes, then strains should exhibit characteristic fractions of persister cells: some strains will consistently have high fractions of persisters (dormant cells), whereas others will have low fractions. Although we found substantial variation in the fraction of persisters between different environmental isolates of E. coli, these fractions were not correlated across antibiotics. Some strains exhibited high persister fractions in one antibiotic, but low persister fractions in a second antibiotic. Surprisingly, no correlation in persister fractions was observed between any two drugs, even for antibiotics with nearly identical modes of action (ciprofloxacin and nalidixic acid). CONCLUSIONS: These data support the hypothesis that there is no single physiological change that determines the persistence level in a population of cells. Instead, the fraction of cells that survive antibiotic treatment (persist) depends critically on the specific antibiotic that is used, suggesting that physiological changes in addition to dormancy can underlie persister phenotypes.
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spelling pubmed-36828932013-06-25 Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli Hofsteenge, Niels van Nimwegen, Erik Silander, Olin K BMC Microbiol Research Article BACKGROUND: Bacterial persistence describes a phenomenon wherein a small subpopulation of cells is able to survive a challenge with high doses of an antibiotic (or other stressor) better than the majority of the population. Previous work has shown that cells that are in a dormant or slow-growing state are persistent to antibiotic treatment and that populations with higher fractions of dormant cells exhibit higher levels of persistence. These data suggest that a major determinant of the fraction of persisters within a population is the rate at which cells enter and exit from dormancy. However, it is not known whether there are physiological changes in addition to dormancy that influence persistence. Here, we use quantitative measurements of persister fractions in a set of environmental isolates of E. coli together with a mathematical model of persister formation to test whether a single general physiological change, such as cell dormancy, can explain the differences in persister phenotypes observed in different strains. RESULTS: If a single physiological change (e.g. cell dormancy) underlies most persister phenotypes, then strains should exhibit characteristic fractions of persister cells: some strains will consistently have high fractions of persisters (dormant cells), whereas others will have low fractions. Although we found substantial variation in the fraction of persisters between different environmental isolates of E. coli, these fractions were not correlated across antibiotics. Some strains exhibited high persister fractions in one antibiotic, but low persister fractions in a second antibiotic. Surprisingly, no correlation in persister fractions was observed between any two drugs, even for antibiotics with nearly identical modes of action (ciprofloxacin and nalidixic acid). CONCLUSIONS: These data support the hypothesis that there is no single physiological change that determines the persistence level in a population of cells. Instead, the fraction of cells that survive antibiotic treatment (persist) depends critically on the specific antibiotic that is used, suggesting that physiological changes in addition to dormancy can underlie persister phenotypes. BioMed Central 2013-02-04 /pmc/articles/PMC3682893/ /pubmed/23379956 http://dx.doi.org/10.1186/1471-2180-13-25 Text en Copyright © 2013 Hofsteenge et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hofsteenge, Niels
van Nimwegen, Erik
Silander, Olin K
Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title_full Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title_fullStr Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title_full_unstemmed Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title_short Quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of E. coli
title_sort quantitative analysis of persister fractions suggests different mechanisms of formation among environmental isolates of e. coli
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682893/
https://www.ncbi.nlm.nih.gov/pubmed/23379956
http://dx.doi.org/10.1186/1471-2180-13-25
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