A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism

Publication type:
Journal article
Metadata:
Autoren
  • Georg Fritz
  • Sebastian Dintner
  • Nicole Simone Treichel
  • Jara Radeck
  • Ulrich Gerland
  • Thorsten Mascher
  • Susanne Gebhard
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000360839400033&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1128/mBio.00975-15
Externe Identifier
  • Clarivate Analytics Document Solution ID: CQ8EN
  • PubMed Identifier: 26199330
ISSN
2150-7511
Ausgabe der Veröffentlichung
4
Zeitschrift
MBIO
Artikelnummer
ARTN e00975-15
Datum der Veröffentlichung
2015
Status
Published
Titel
A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism
Sub types
  • Article
Ausgabe der Zeitschrift
6

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>ABSTRACT</jats:title> <jats:p> Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as “concentration sensors,” or by responding to downstream effects on bacterial physiology, such as structural damage to the cell. Here, we describe a novel, alternative signaling mechanism that effectively implements a “flux sensor” to regulate antibiotic resistance. It relies on a sensory complex consisting of a histidine kinase and an ABC transporter, in which the transporter fulfills the dual role of both the sensor of the antibiotic and the mediator of resistance against it. Combining systems biological modeling with <jats:italic>in vivo</jats:italic> experimentation, we show that these systems in fact respond to changes in activity of individual resistance transporters rather than to changes in the antibiotic concentration. Our model shows that the cell thereby adjusts the rate of <jats:italic>de novo</jats:italic> transporter synthesis to precisely the level needed for protection. Such a flux-sensing mechanism may serve as a cost-efficient produce-to-demand strategy, controlling a widely conserved class of antibiotic resistance systems. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> Bacteria have to be able to accurately perceive their environment to allow adaptation to changing conditions. This is usually accomplished by sensing the concentrations of beneficial or harmful substances or by measuring the effect of the prevailing conditions on the cell. Here we show the existence of a new way of sensing the environment, where the bacteria monitor the activity of an antibiotic resistance transporter. Such a “flux-sensing” mechanism allows the cell to detect its current capacity to deal with the antibiotic challenge and thus precisely respond to the need for more transporters. We propose that this is a cost-efficient way of regulating antibiotic resistance on demand. </jats:p>
Autoren
  • Georg Fritz
  • Sebastian Dintner
  • Nicole Simone Treichel
  • Jara Radeck
  • Ulrich Gerland
  • Thorsten Mascher
  • Susanne Gebhard
DOI
10.1128/mbio.00975-15
Editoren
  • George L Drusano
eISSN
2150-7511
ISSN
2161-2129
Ausgabe der Veröffentlichung
4
Zeitschrift
mBio
Sprache
en
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
American Society for Microbiology
Herausgeber URL
http://dx.doi.org/10.1128/mbio.00975-15
Datum der Datenerfassung
2022
Titel
A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism
Ausgabe der Zeitschrift
6

Data source: Crossref

Abstract
<h4>Unlabelled</h4>Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as "concentration sensors," or by responding to downstream effects on bacterial physiology, such as structural damage to the cell. Here, we describe a novel, alternative signaling mechanism that effectively implements a "flux sensor" to regulate antibiotic resistance. It relies on a sensory complex consisting of a histidine kinase and an ABC transporter, in which the transporter fulfills the dual role of both the sensor of the antibiotic and the mediator of resistance against it. Combining systems biological modeling with in vivo experimentation, we show that these systems in fact respond to changes in activity of individual resistance transporters rather than to changes in the antibiotic concentration. Our model shows that the cell thereby adjusts the rate of de novo transporter synthesis to precisely the level needed for protection. Such a flux-sensing mechanism may serve as a cost-efficient produce-to-demand strategy, controlling a widely conserved class of antibiotic resistance systems.<h4>Importance</h4>Bacteria have to be able to accurately perceive their environment to allow adaptation to changing conditions. This is usually accomplished by sensing the concentrations of beneficial or harmful substances or by measuring the effect of the prevailing conditions on the cell. Here we show the existence of a new way of sensing the environment, where the bacteria monitor the activity of an antibiotic resistance transporter. Such a "flux-sensing" mechanism allows the cell to detect its current capacity to deal with the antibiotic challenge and thus precisely respond to the need for more transporters. We propose that this is a cost-efficient way of regulating antibiotic resistance on demand.
Addresses
  • Department Biology I, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany Arnold Sommerfeld Center for Theoretical Physics, Ludwig-Maximilians-Universität München, Munich, Germany.
Autoren
  • Georg Fritz
  • Sebastian Dintner
  • Nicole Simone Treichel
  • Jara Radeck
  • Ulrich Gerland
  • Thorsten Mascher
  • Susanne Gebhard
DOI
10.1128/mbio.00975-15
eISSN
2150-7511
Externe Identifier
  • PubMed Identifier: 26199330
  • PubMed Central ID: PMC4513084
Open access
true
ISSN
2150-7511
Ausgabe der Veröffentlichung
4
Zeitschrift
mBio
Schlüsselwörter
  • Bacteria
  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Systems Biology
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial
  • Models, Biological
Sprache
eng
Medium
Electronic
Online publication date
2015
Open access status
Open Access
Paginierung
e00975
Datum der Veröffentlichung
2015
Status
Published
Publisher licence
CC BY-NC-SA
Datum der Datenerfassung
2015
Titel
A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
6

Files

https://mbio.asm.org/content/mbio/6/4/e00975-15.full.pdf https://europepmc.org/articles/PMC4513084?pdf=render

Data source: Europe PubMed Central

Abstract
UNLABELLED: Sensing of and responding to environmental changes are of vital importance for microbial cells. Consequently, bacteria have evolved a plethora of signaling systems that usually sense biochemical cues either via direct ligand binding, thereby acting as "concentration sensors," or by responding to downstream effects on bacterial physiology, such as structural damage to the cell. Here, we describe a novel, alternative signaling mechanism that effectively implements a "flux sensor" to regulate antibiotic resistance. It relies on a sensory complex consisting of a histidine kinase and an ABC transporter, in which the transporter fulfills the dual role of both the sensor of the antibiotic and the mediator of resistance against it. Combining systems biological modeling with in vivo experimentation, we show that these systems in fact respond to changes in activity of individual resistance transporters rather than to changes in the antibiotic concentration. Our model shows that the cell thereby adjusts the rate of de novo transporter synthesis to precisely the level needed for protection. Such a flux-sensing mechanism may serve as a cost-efficient produce-to-demand strategy, controlling a widely conserved class of antibiotic resistance systems. IMPORTANCE: Bacteria have to be able to accurately perceive their environment to allow adaptation to changing conditions. This is usually accomplished by sensing the concentrations of beneficial or harmful substances or by measuring the effect of the prevailing conditions on the cell. Here we show the existence of a new way of sensing the environment, where the bacteria monitor the activity of an antibiotic resistance transporter. Such a "flux-sensing" mechanism allows the cell to detect its current capacity to deal with the antibiotic challenge and thus precisely respond to the need for more transporters. We propose that this is a cost-efficient way of regulating antibiotic resistance on demand.
Autoren
  • Georg Fritz
  • Sebastian Dintner
  • Nicole Simone Treichel
  • Jara Radeck
  • Ulrich Gerland
  • Thorsten Mascher
  • Susanne Gebhard
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26199330
DOI
10.1128/mBio.00975-15
eISSN
2150-7511
Externe Identifier
  • PubMed Central ID: PMC4513084
Ausgabe der Veröffentlichung
4
Zeitschrift
mBio
Schlüsselwörter
  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Bacteria
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial
  • Models, Biological
  • Systems Biology
Sprache
eng
Country
United States
Paginierung
e00975
PII
mBio.00975-15
Datum der Veröffentlichung
2015
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2016
Titel
A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
6

Data source: PubMed

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