A new way of sensing: need-based activation of antibiotic resistance by a flux-sensing mechanism

Georg Fritz, Sebastian Dintner, Nicole Treichel, Jara Radeck, Ulrich Gerland, Thorsten Mascher, Susanne Gebhard

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27 Citations (Scopus)
31 Downloads (Pure)

Abstract

Sensing of and responding to environmental changes is 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 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 between 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.
Original languageEnglish
Article numbere00975-15
Pages (from-to)1-9
Number of pages9
JournalmBio
Volume6
Issue number4
Early online date21 Jul 2015
DOIs
Publication statusPublished - 31 Aug 2015

Keywords

  • Stimulus Perception
  • Two-Component System
  • ABC Transporter
  • Quantitative Modeling
  • Regulation Strategy

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    Fritz, G., Dintner, S., Treichel, N., Radeck, J., Gerland, U., Mascher, T., & Gebhard, S. (2015). A new way of sensing: need-based activation of antibiotic resistance by a flux-sensing mechanism. mBio, 6(4), 1-9. [e00975-15]. https://doi.org/10.1128/mBio.00975-15