Bacterial persistence is an active sigma(S) stress response to metabolic flux limitation
File(s)
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2016-09-01
Date Acceptance
2016-08-23
Citation
Molecular Systems Biology, 2016, 12 (9), pp.1-18
ISSN
1744-4292
Publisher
European Molecular Biology Organization
Start Page
1
End Page
18
Journal / Book Title
Molecular Systems Biology
Volume
12
Issue
9
Copyright Statement
© 2016 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under theterms of the Creative Commons Attribution 4.0License, which permits use, distribution and reproduc-tion in any medium, provided the original work isproperly cited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000385410200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Escherichia coli
metabolism
persistence
proteomics
stress response
MEDIATE ANTIBIOTIC TOLERANCE
ESCHERICHIA-COLI
GENE-EXPRESSION
RIBONUCLEIC-ACID
MESSENGER-RNA
STARVATION
CELLS
GROWTH
PROTEIN
PPGPP
Publication Status
Published
Article Number
ARTN 882
Date Publish Online
2016-09-21