Temporal order and precision of complex stress responses in individual bacteria

Abstract Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual pro...

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Main Authors: Karin Mitosch, Georg Rieckh, Tobias Bollenbach
Format: Article
Language:English
Published: Springer Nature 2019-02-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20188470
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author Karin Mitosch
Georg Rieckh
Tobias Bollenbach
author_facet Karin Mitosch
Georg Rieckh
Tobias Bollenbach
author_sort Karin Mitosch
collection DOAJ
description Abstract Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.
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spelling doaj-art-defd8ab26a4c4e198e0955c4ea5c4d392025-08-20T03:46:32ZengSpringer NatureMolecular Systems Biology1744-42922019-02-0115211510.15252/msb.20188470Temporal order and precision of complex stress responses in individual bacteriaKarin Mitosch0Georg Rieckh1Tobias Bollenbach2IST AustriaIST AustriaUniversity of CologneAbstract Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.https://doi.org/10.15252/msb.20188470antibioticsbacterial stress responsegene expression timingmicrofluidicssingle‐cell measurements
spellingShingle Karin Mitosch
Georg Rieckh
Tobias Bollenbach
Temporal order and precision of complex stress responses in individual bacteria
Molecular Systems Biology
antibiotics
bacterial stress response
gene expression timing
microfluidics
single‐cell measurements
title Temporal order and precision of complex stress responses in individual bacteria
title_full Temporal order and precision of complex stress responses in individual bacteria
title_fullStr Temporal order and precision of complex stress responses in individual bacteria
title_full_unstemmed Temporal order and precision of complex stress responses in individual bacteria
title_short Temporal order and precision of complex stress responses in individual bacteria
title_sort temporal order and precision of complex stress responses in individual bacteria
topic antibiotics
bacterial stress response
gene expression timing
microfluidics
single‐cell measurements
url https://doi.org/10.15252/msb.20188470
work_keys_str_mv AT karinmitosch temporalorderandprecisionofcomplexstressresponsesinindividualbacteria
AT georgrieckh temporalorderandprecisionofcomplexstressresponsesinindividualbacteria
AT tobiasbollenbach temporalorderandprecisionofcomplexstressresponsesinindividualbacteria