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Resuscitation dynamics reveal persister partitioning after antibiotic treatment

Bacteria can survive antibiotics by forming dormant, drug‐tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single‐cell nature makes it difficult to investigate. We tracked the re...

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Autores principales: Fang, Xin, Allison, Kyle R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090945/
https://www.ncbi.nlm.nih.gov/pubmed/36866643
http://dx.doi.org/10.15252/msb.202211320
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author Fang, Xin
Allison, Kyle R
author_facet Fang, Xin
Allison, Kyle R
author_sort Fang, Xin
collection PubMed
description Bacteria can survive antibiotics by forming dormant, drug‐tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single‐cell nature makes it difficult to investigate. We tracked the resuscitation of individual persisters by microscopy after ampicillin treatment and, by characterizing their dynamics, discovered that Escherichia coli and Salmonella enterica persisters resuscitate exponentially rather than stochastically. We demonstrated that the key parameters controlling resuscitation map to the ampicillin concentration during treatment and efflux during resuscitation. Consistently, we observed many persister progeny have structural defects and transcriptional responses indicative of cellular damage, for both β‐lactam and quinolone antibiotics. During resuscitation, damaged persisters partition unevenly, generating both healthy daughter cells and defective ones. This persister partitioning phenomenon was observed in S. enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and an E. coli urinary tract infection (UTI) isolate. It was also observed in the standard persister assay and after in situ treatment of a clinical UTI sample. This study reveals novel properties of resuscitation and indicates that persister partitioning may be a survival strategy in bacteria that lack genetic resistance.
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spelling pubmed-100909452023-04-13 Resuscitation dynamics reveal persister partitioning after antibiotic treatment Fang, Xin Allison, Kyle R Mol Syst Biol Articles Bacteria can survive antibiotics by forming dormant, drug‐tolerant persisters. Persisters can resuscitate from dormancy after treatment and prolong infections. Resuscitation is thought to occur stochastically, but its transient, single‐cell nature makes it difficult to investigate. We tracked the resuscitation of individual persisters by microscopy after ampicillin treatment and, by characterizing their dynamics, discovered that Escherichia coli and Salmonella enterica persisters resuscitate exponentially rather than stochastically. We demonstrated that the key parameters controlling resuscitation map to the ampicillin concentration during treatment and efflux during resuscitation. Consistently, we observed many persister progeny have structural defects and transcriptional responses indicative of cellular damage, for both β‐lactam and quinolone antibiotics. During resuscitation, damaged persisters partition unevenly, generating both healthy daughter cells and defective ones. This persister partitioning phenomenon was observed in S. enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and an E. coli urinary tract infection (UTI) isolate. It was also observed in the standard persister assay and after in situ treatment of a clinical UTI sample. This study reveals novel properties of resuscitation and indicates that persister partitioning may be a survival strategy in bacteria that lack genetic resistance. John Wiley and Sons Inc. 2023-03-03 /pmc/articles/PMC10090945/ /pubmed/36866643 http://dx.doi.org/10.15252/msb.202211320 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Fang, Xin
Allison, Kyle R
Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title_full Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title_fullStr Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title_full_unstemmed Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title_short Resuscitation dynamics reveal persister partitioning after antibiotic treatment
title_sort resuscitation dynamics reveal persister partitioning after antibiotic treatment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090945/
https://www.ncbi.nlm.nih.gov/pubmed/36866643
http://dx.doi.org/10.15252/msb.202211320
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