Bacterial persistence is an active σS stress response to metabolic flux limitation

While persisters are a health threat due to their transient antibiotic tolerance, little is known about their phenotype and what actually causes persistence. Using a new method for persister generation and high‐throughput methods, we comprehensively mapped the molecular phenotype of Escherichia coli...

Full description

Bibliographic Details
Main Authors:	Radzikowski, Jakub Leszek, Vedelaar, Silke, Siegel, David, Ortega, Álvaro Dario, Schmidt, Alexander, Heinemann, Matthias
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043093/

id	pubmed-5043093
recordtype	oai_dc
spelling	pubmed-50430932016-10-18 Bacterial persistence is an active σS stress response to metabolic flux limitation Radzikowski, Jakub Leszek Vedelaar, Silke Siegel, David Ortega, Álvaro Dario Schmidt, Alexander Heinemann, Matthias Articles While persisters are a health threat due to their transient antibiotic tolerance, little is known about their phenotype and what actually causes persistence. Using a new method for persister generation and high‐throughput methods, we comprehensively mapped the molecular phenotype of Escherichia coli during the entry and in the state of persistence in nutrient‐rich conditions. The persister proteome is characterized by σS‐mediated stress response and a shift to catabolism, a proteome that starved cells tried to but could not reach due to absence of a carbon and energy source. Metabolism of persisters is geared toward energy production, with depleted metabolite pools. We developed and experimentally verified a model, in which persistence is established through a system‐level feedback: Strong perturbations of metabolic homeostasis cause metabolic fluxes to collapse, prohibiting adjustments toward restoring homeostasis. This vicious cycle is stabilized and modulated by high ppGpp levels, toxin/anti‐toxin systems, and the σS‐mediated stress response. Our system‐level model consistently integrates past findings with our new data, thereby providing an important basis for future research on persisters. John Wiley and Sons Inc. 2016-09-21 /pmc/articles/PMC5043093/ /pubmed/27655400 http://dx.doi.org/10.15252/msb.20166998 Text en © 2016 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Radzikowski, Jakub Leszek Vedelaar, Silke Siegel, David Ortega, Álvaro Dario Schmidt, Alexander Heinemann, Matthias
spellingShingle	Radzikowski, Jakub Leszek Vedelaar, Silke Siegel, David Ortega, Álvaro Dario Schmidt, Alexander Heinemann, Matthias Bacterial persistence is an active σS stress response to metabolic flux limitation
author_facet	Radzikowski, Jakub Leszek Vedelaar, Silke Siegel, David Ortega, Álvaro Dario Schmidt, Alexander Heinemann, Matthias
author_sort	Radzikowski, Jakub Leszek
title	Bacterial persistence is an active σS stress response to metabolic flux limitation
title_short	Bacterial persistence is an active σS stress response to metabolic flux limitation
title_full	Bacterial persistence is an active σS stress response to metabolic flux limitation
title_fullStr	Bacterial persistence is an active σS stress response to metabolic flux limitation
title_full_unstemmed	Bacterial persistence is an active σS stress response to metabolic flux limitation
title_sort	bacterial persistence is an active σs stress response to metabolic flux limitation
description	While persisters are a health threat due to their transient antibiotic tolerance, little is known about their phenotype and what actually causes persistence. Using a new method for persister generation and high‐throughput methods, we comprehensively mapped the molecular phenotype of Escherichia coli during the entry and in the state of persistence in nutrient‐rich conditions. The persister proteome is characterized by σS‐mediated stress response and a shift to catabolism, a proteome that starved cells tried to but could not reach due to absence of a carbon and energy source. Metabolism of persisters is geared toward energy production, with depleted metabolite pools. We developed and experimentally verified a model, in which persistence is established through a system‐level feedback: Strong perturbations of metabolic homeostasis cause metabolic fluxes to collapse, prohibiting adjustments toward restoring homeostasis. This vicious cycle is stabilized and modulated by high ppGpp levels, toxin/anti‐toxin systems, and the σS‐mediated stress response. Our system‐level model consistently integrates past findings with our new data, thereby providing an important basis for future research on persisters.
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043093/
_version_	1613666514294013952

Bacterial persistence is an active σS stress response to metabolic flux limitation

Similar Items