---
_id: '12261'
abstract:
- lang: eng
  text: 'Dose–response relationships are a general concept for quantitatively describing
    biological systems across multiple scales, from the molecular to the whole-cell
    level. A clinically relevant example is the bacterial growth response to antibiotics,
    which is routinely characterized by dose–response curves. The shape of the dose–response
    curve varies drastically between antibiotics and plays a key role in treatment,
    drug interactions, and resistance evolution. However, the mechanisms shaping the
    dose–response curve remain largely unclear. Here, we show in Escherichia coli
    that the distinctively shallow dose–response curve of the antibiotic trimethoprim
    is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth,
    which in turn weakens the effect of this antibiotic. At the molecular level, this
    feedback is caused by the upregulation of the drug target dihydrofolate reductase
    (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim
    but follows a universal trend line that depends primarily on the growth rate,
    irrespective of its cause. Rewiring the feedback loop alters the dose–response
    curve in a predictable manner, which we corroborate using a mathematical model
    of cellular resource allocation and growth. Our results indicate that growth-mediated
    feedback loops may shape drug responses more generally and could be exploited
    to design evolutionary traps that enable selection against drug resistance.'
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This work was in part supported by Human Frontier Science Program
  GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund
  (FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research
  Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research
  and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352.
  We wouldlike to thank the Bollenbach group for regular fruitful discussions. We
  areparticularly thankful for the technical assistance of Booshini Fernando andfor
  discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor
  Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth
  monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba
  Machine Shop for their support inbuilding a housing for the stacker of the plate
  reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful
  to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open
  Accessfunding enabled and organized by Projekt DEAL.
article_number: e10490
article_processing_charge: No
article_type: original
author:
- first_name: Andreas
  full_name: Angermayr, Andreas
  id: 4677C796-F248-11E8-B48F-1D18A9856A87
  last_name: Angermayr
  orcid: 0000-0001-8619-2223
- first_name: Tin Yau
  full_name: Pang, Tin Yau
  last_name: Pang
- first_name: Guillaume
  full_name: Chevereau, Guillaume
  last_name: Chevereau
- first_name: Karin
  full_name: Mitosch, Karin
  id: 39B66846-F248-11E8-B48F-1D18A9856A87
  last_name: Mitosch
- first_name: Martin J
  full_name: Lercher, Martin J
  last_name: Lercher
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated
    negative feedback shapes quantitative antibiotic response. <i>Molecular Systems
    Biology</i>. 2022;18(9). doi:<a href="https://doi.org/10.15252/msb.202110490">10.15252/msb.202110490</a>
  apa: Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., &#38;
    Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative
    antibiotic response. <i>Molecular Systems Biology</i>. Embo Press. <a href="https://doi.org/10.15252/msb.202110490">https://doi.org/10.15252/msb.202110490</a>
  chicago: Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin
    J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes
    Quantitative Antibiotic Response.” <i>Molecular Systems Biology</i>. Embo Press,
    2022. <a href="https://doi.org/10.15252/msb.202110490">https://doi.org/10.15252/msb.202110490</a>.
  ieee: A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M.
    T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic
    response,” <i>Molecular Systems Biology</i>, vol. 18, no. 9. Embo Press, 2022.
  ista: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022.
    Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular
    Systems Biology. 18(9), e10490.
  mla: Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative
    Antibiotic Response.” <i>Molecular Systems Biology</i>, vol. 18, no. 9, e10490,
    Embo Press, 2022, doi:<a href="https://doi.org/10.15252/msb.202110490">10.15252/msb.202110490</a>.
  short: A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach,
    Molecular Systems Biology 18 (2022).
date_created: 2023-01-16T09:58:34Z
date_published: 2022-09-01T00:00:00Z
date_updated: 2023-08-04T09:51:49Z
day: '01'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.15252/msb.202110490
external_id:
  isi:
  - '000856482800001'
file:
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  checksum: 8b1d8f5ea20c8408acf466435fb6ae01
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  creator: dernst
  date_created: 2023-01-30T09:49:55Z
  date_updated: 2023-01-30T09:49:55Z
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file_date_updated: 2023-01-30T09:49:55Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '9'
keyword:
- Applied Mathematics
- Computational Theory and Mathematics
- General Agricultural and Biological Sciences
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- Information Systems
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Molecular Systems Biology
publication_identifier:
  eissn:
  - 1744-4292
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Growth‐mediated negative feedback shapes quantitative antibiotic response
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2022'
...
---
_id: '6046'
abstract:
- lang: eng
  text: 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.
acknowledged_ssus:
- _id: Bio
article_number: e8470
article_processing_charge: No
author:
- first_name: Karin
  full_name: Mitosch, Karin
  id: 39B66846-F248-11E8-B48F-1D18A9856A87
  last_name: Mitosch
- first_name: Georg
  full_name: Rieckh, Georg
  id: 34DA8BD6-F248-11E8-B48F-1D18A9856A87
  last_name: Rieckh
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex
    stress responses in individual bacteria. <i>Molecular systems biology</i>. 2019;15(2).
    doi:<a href="https://doi.org/10.15252/msb.20188470">10.15252/msb.20188470</a>
  apa: Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2019). Temporal order and
    precision of complex stress responses in individual bacteria. <i>Molecular Systems
    Biology</i>. Embo Press. <a href="https://doi.org/10.15252/msb.20188470">https://doi.org/10.15252/msb.20188470</a>
  chicago: Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order
    and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular
    Systems Biology</i>. Embo Press, 2019. <a href="https://doi.org/10.15252/msb.20188470">https://doi.org/10.15252/msb.20188470</a>.
  ieee: K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision
    of complex stress responses in individual bacteria,” <i>Molecular systems biology</i>,
    vol. 15, no. 2. Embo Press, 2019.
  ista: Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of
    complex stress responses in individual bacteria. Molecular systems biology. 15(2),
    e8470.
  mla: Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses
    in Individual Bacteria.” <i>Molecular Systems Biology</i>, vol. 15, no. 2, e8470,
    Embo Press, 2019, doi:<a href="https://doi.org/10.15252/msb.20188470">10.15252/msb.20188470</a>.
  short: K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).
date_created: 2019-02-24T22:59:18Z
date_published: 2019-02-14T00:00:00Z
date_updated: 2023-08-24T14:49:53Z
day: '14'
department:
- _id: GaTk
doi: 10.15252/msb.20188470
external_id:
  isi:
  - '000459628300003'
  pmid:
  - '30765425'
intvolume: '        15'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pubmed/30765425
month: '02'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
  grant_number: RGP0042/2013
  name: Revealing the fundamental limits of cell growth
publication: Molecular systems biology
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Temporal order and precision of complex stress responses in individual bacteria
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...
---
_id: '818'
abstract:
- lang: eng
  text: 'Antibiotics have diverse effects on bacteria, including massive changes in
    bacterial gene expression. Whereas the gene expression changes under many antibiotics
    have been measured, the temporal organization of these responses and their dependence
    on the bacterial growth rate are unclear. As described in Chapter 1, we quantified
    the temporal gene expression changes in the bacterium Escherichia coli in response
    to the sudden exposure to antibiotics using a fluorescent reporter library and
    a robotic system. Our data show temporally structured gene expression responses,
    with response times for individual genes ranging from tens of minutes to several
    hours. We observed that many stress response genes were activated in response
    to antibiotics. As certain stress responses cross-protect bacteria from other
    stressors, we then asked whether cellular responses to antibiotics have a similar
    protective role in Chapter 2. Indeed, we found that the trimethoprim-induced acid
    stress response protects bacteria from subsequent acid stress. We combined microfluidics
    with time-lapse imaging to monitor survival, intracellular pH, and acid stress
    response in single cells. This approach revealed that the variable expression
    of the acid resistance operon gadBC strongly correlates with single-cell survival
    time. Cells with higher gadBC expression following trimethoprim maintain higher
    intracellular pH and survive the acid stress longer. Overall, we provide a way
    to identify single-cell cross-protection between antibiotics and environmental
    stressors from temporal gene expression data, and show how antibiotics can increase
    bacterial fitness in changing environments. While gene expression changes to antibiotics
    show a clear temporal structure at the population-level, it is unclear whether
    this clear temporal order is followed by every single cell. Using dual-reporter
    strains described in Chapter 3, we measured gene expression dynamics of promoter
    pairs in the same cells using microfluidics and microscopy. Chapter 4 shows that
    the oxidative stress response and the DNA stress response showed little timing
    variability and a clear temporal order under the antibiotic nitrofurantoin. In
    contrast, the acid stress response under trimethoprim ran independently from all
    other activated response programs including the DNA stress response, which showed
    particularly high timing variability in this stress condition. In summary, this
    approach provides insight into the temporal organization of gene expression programs
    at the single-cell level and suggests dependencies between response programs and
    the underlying variability-introducing mechanisms. Altogether, this work advances
    our understanding of the diverse effects that antibiotics have on bacteria. These
    results were obtained by taking into account gene expression dynamics, which allowed
    us to identify general principles, molecular mechanisms, and dependencies between
    genes. Our findings may have implications for infectious disease treatments, and
    microbial communities in the human body and in nature. '
acknowledgement: 'First of all, I would like to express great gratitude to my PhD
  supervisor Tobias Bollenbach. Through his open and trusting attitude I had the freedom
  to explore different scientific directions during this project, and follow the research
  lines of my interest. I am thankful for constructive and often extensive discussions
  and his support and commitment during the different stages of my PhD. I want to
  thank my committee members, Călin Guet, Terry Hwa and Nassos Typas for their interest
  and their valuable input to this project. Special thanks to Nassos for career guidance,
  and for accepting me in his lab. A big thank you goes to the past, present and affiliated
  members of the Bollenbach group: Guillaume Chevereau, Marjon de Vos, Marta Lukačišinová,
  Veronika Bierbaum, Qi Qin, Marcin Zagórski, Martin Lukačišin, Andreas Angermayr,
  Bor Kavčič, Julia Tischler, Dilay Ayhan, Jaroslav Ferenc, and Georg Rieckh. I enjoyed
  working and discussing with you very much and I will miss our lengthy group meetings,
  our inspiring journal clubs, and our common lunches. Special thanks to Bor for great
  mental and professional support during the hard months of thesis writing, and to
  Marta for very creative times during the beginning of our PhDs. May the ‘Bacterial
  Survival Guide’ decorate the walls of IST forever! A great thanks to my friend and
  collaborator Georg Rieckh for his enthusiasm and for getting so involved in these
  projects, for his endurance and for his company throughout the years. Thanks to
  the FriSBi crowd at IST Austria for interesting meetings and discussions. In particular
  I want to thank Magdalena Steinrück, and Anna Andersson for inspiring exchange,
  and enjoyable time together. Thanks to everybody who contributed to the cover for
  Cell Systems: The constructive input from Tobias Bollenbach, Bor Kavčič, Georg Rieckh,
  Marta Lukačišinová, and Sebastian Nozzi, and the professional implementation by
  the graphic designer Martina Markus from the University of Cologne. Thanks to all
  my office mates in the first floor Bertalanffy building throughout the years: for
  ensuring a pleasant working atmosphere, and for your company! In general, I want
  to thank all the people that make IST such a great environment, with the many possibilities
  to shape our own social and research environment. I want to thank my family for
  all kind of practical support during the years, and my second family in Argentina
  for their enthusiasm. Thanks to my brother Bernhard and my sister Martina for being
  great siblings, and to Helena and Valentin for the joy you brought to my life. My
  deep gratitude goes to Sebastian Nozzi, for constant support, patience, love and
  for believing in me. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Karin
  full_name: Mitosch, Karin
  id: 39B66846-F248-11E8-B48F-1D18A9856A87
  last_name: Mitosch
citation:
  ama: Mitosch K. Timing, variability and cross-protection in bacteria – insights
    from dynamic gene expression responses to antibiotics. 2017. doi:<a href="https://doi.org/10.15479/AT:ISTA:th_862">10.15479/AT:ISTA:th_862</a>
  apa: Mitosch, K. (2017). <i>Timing, variability and cross-protection in bacteria
    – insights from dynamic gene expression responses to antibiotics</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:th_862">https://doi.org/10.15479/AT:ISTA:th_862</a>
  chicago: Mitosch, Karin. “Timing, Variability and Cross-Protection in Bacteria –
    Insights from Dynamic Gene Expression Responses to Antibiotics.” Institute of
    Science and Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:th_862">https://doi.org/10.15479/AT:ISTA:th_862</a>.
  ieee: K. Mitosch, “Timing, variability and cross-protection in bacteria – insights
    from dynamic gene expression responses to antibiotics,” Institute of Science and
    Technology Austria, 2017.
  ista: Mitosch K. 2017. Timing, variability and cross-protection in bacteria – insights
    from dynamic gene expression responses to antibiotics. Institute of Science and
    Technology Austria.
  mla: Mitosch, Karin. <i>Timing, Variability and Cross-Protection in Bacteria – Insights
    from Dynamic Gene Expression Responses to Antibiotics</i>. Institute of Science
    and Technology Austria, 2017, doi:<a href="https://doi.org/10.15479/AT:ISTA:th_862">10.15479/AT:ISTA:th_862</a>.
  short: K. Mitosch, Timing, Variability and Cross-Protection in Bacteria – Insights
    from Dynamic Gene Expression Responses to Antibiotics, Institute of Science and
    Technology Austria, 2017.
date_created: 2018-12-11T11:48:40Z
date_published: 2017-09-27T00:00:00Z
date_updated: 2023-09-07T12:00:26Z
day: '27'
ddc:
- '571'
- '579'
degree_awarded: PhD
department:
- _id: ToBo
doi: 10.15479/AT:ISTA:th_862
file:
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  creator: dernst
  date_created: 2019-04-05T08:48:51Z
  date_updated: 2020-07-14T12:48:09Z
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month: '09'
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page: '113'
publication_identifier:
  issn:
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publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6831'
pubrep_id: '862'
related_material:
  record:
  - id: '2001'
    relation: part_of_dissertation
    status: public
  - id: '666'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
title: Timing, variability and cross-protection in bacteria – insights from dynamic
  gene expression responses to antibiotics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2017'
...
---
_id: '666'
abstract:
- lang: eng
  text: Antibiotics elicit drastic changes in microbial gene expression, including
    the induction of stress response genes. While certain stress responses are known
    to “cross-protect” bacteria from other stressors, it is unclear whether cellular
    responses to antibiotics have a similar protective role. By measuring the genome-wide
    transcriptional response dynamics of Escherichia coli to four antibiotics, we
    found that trimethoprim induces a rapid acid stress response that protects bacteria
    from subsequent exposure to acid. Combining microfluidics with time-lapse imaging
    to monitor survival and acid stress response in single cells revealed that the
    noisy expression of the acid resistance operon gadBC correlates with single-cell
    survival. Cells with higher gadBC expression following trimethoprim maintain higher
    intracellular pH and survive the acid stress longer. The seemingly random single-cell
    survival under acid stress can therefore be predicted from gadBC expression and
    rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap
    for identifying the molecular mechanisms of single-cell cross-protection between
    antibiotics and other stressors.
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Karin
  full_name: Mitosch, Karin
  id: 39B66846-F248-11E8-B48F-1D18A9856A87
  last_name: Mitosch
- first_name: Georg
  full_name: Rieckh, Georg
  id: 34DA8BD6-F248-11E8-B48F-1D18A9856A87
  last_name: Rieckh
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Mitosch K, Rieckh G, Bollenbach MT. Noisy response to antibiotic stress predicts
    subsequent single cell survival in an acidic environment. <i>Cell Systems</i>.
    2017;4(4):393-403. doi:<a href="https://doi.org/10.1016/j.cels.2017.03.001">10.1016/j.cels.2017.03.001</a>
  apa: Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2017). Noisy response to
    antibiotic stress predicts subsequent single cell survival in an acidic environment.
    <i>Cell Systems</i>. Cell Press. <a href="https://doi.org/10.1016/j.cels.2017.03.001">https://doi.org/10.1016/j.cels.2017.03.001</a>
  chicago: Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Noisy Response
    to Antibiotic Stress Predicts Subsequent Single Cell Survival in an Acidic Environment.”
    <i>Cell Systems</i>. Cell Press, 2017. <a href="https://doi.org/10.1016/j.cels.2017.03.001">https://doi.org/10.1016/j.cels.2017.03.001</a>.
  ieee: K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Noisy response to antibiotic
    stress predicts subsequent single cell survival in an acidic environment,” <i>Cell
    Systems</i>, vol. 4, no. 4. Cell Press, pp. 393–403, 2017.
  ista: Mitosch K, Rieckh G, Bollenbach MT. 2017. Noisy response to antibiotic stress
    predicts subsequent single cell survival in an acidic environment. Cell Systems.
    4(4), 393–403.
  mla: Mitosch, Karin, et al. “Noisy Response to Antibiotic Stress Predicts Subsequent
    Single Cell Survival in an Acidic Environment.” <i>Cell Systems</i>, vol. 4, no.
    4, Cell Press, 2017, pp. 393–403, doi:<a href="https://doi.org/10.1016/j.cels.2017.03.001">10.1016/j.cels.2017.03.001</a>.
  short: K. Mitosch, G. Rieckh, M.T. Bollenbach, Cell Systems 4 (2017) 393–403.
date_created: 2018-12-11T11:47:48Z
date_published: 2017-04-26T00:00:00Z
date_updated: 2023-09-07T12:00:25Z
day: '26'
ddc:
- '576'
- '610'
department:
- _id: ToBo
- _id: GaTk
doi: 10.1016/j.cels.2017.03.001
ec_funded: 1
file:
- access_level: open_access
  checksum: 04ff20011c3d9a601c514aa999a5fe1a
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:13:54Z
  date_updated: 2020-07-14T12:47:35Z
  file_id: '5041'
  file_name: IST-2017-901-v1+1_1-s2.0-S2405471217300868-main.pdf
  file_size: 2438660
  relation: main_file
file_date_updated: 2020-07-14T12:47:35Z
has_accepted_license: '1'
intvolume: '         4'
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 393 - 403
project:
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '303507'
  name: Optimality principles in responses to antibiotics
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
  grant_number: RGP0042/2013
  name: Revealing the fundamental limits of cell growth
publication: Cell Systems
publication_identifier:
  issn:
  - '24054712'
publication_status: published
publisher: Cell Press
publist_id: '7061'
pubrep_id: '901'
quality_controlled: '1'
related_material:
  record:
  - id: '818'
    relation: dissertation_contains
    status: public
scopus_import: 1
status: public
title: Noisy response to antibiotic stress predicts subsequent single cell survival
  in an acidic environment
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 4
year: '2017'
...
---
_id: '2001'
abstract:
- lang: eng
  text: Antibiotics affect bacterial cell physiology at many levels. Rather than just
    compensating for the direct cellular defects caused by the drug, bacteria respond
    to antibiotics by changing their morphology, macromolecular composition, metabolism,
    gene expression and possibly even their mutation rate. Inevitably, these processes
    affect each other, resulting in a complex response with changes in the expression
    of numerous genes. Genome‐wide approaches can thus help in gaining a comprehensive
    understanding of bacterial responses to antibiotics. In addition, a combination
    of experimental and theoretical approaches is needed for identifying general principles
    that underlie these responses. Here, we review recent progress in our understanding
    of bacterial responses to antibiotics and their combinations, focusing on effects
    at the levels of growth rate and gene expression. We concentrate on studies performed
    in controlled laboratory conditions, which combine promising experimental techniques
    with quantitative data analysis and mathematical modeling. While these basic research
    approaches are not immediately applicable in the clinic, uncovering the principles
    and mechanisms underlying bacterial responses to antibiotics may, in the long
    term, contribute to the development of new treatment strategies to cope with and
    prevent the rise of resistant pathogenic bacteria.
author:
- first_name: Karin
  full_name: Mitosch, Karin
  id: 39B66846-F248-11E8-B48F-1D18A9856A87
  last_name: Mitosch
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Mitosch K, Bollenbach MT. Bacterial responses to antibiotics and their combinations.
    <i>Environmental Microbiology Reports</i>. 2014;6(6):545-557. doi:<a href="https://doi.org/10.1111/1758-2229.12190">10.1111/1758-2229.12190</a>
  apa: Mitosch, K., &#38; Bollenbach, M. T. (2014). Bacterial responses to antibiotics
    and their combinations. <i>Environmental Microbiology Reports</i>. Wiley. <a href="https://doi.org/10.1111/1758-2229.12190">https://doi.org/10.1111/1758-2229.12190</a>
  chicago: Mitosch, Karin, and Mark Tobias Bollenbach. “Bacterial Responses to Antibiotics
    and Their Combinations.” <i>Environmental Microbiology Reports</i>. Wiley, 2014.
    <a href="https://doi.org/10.1111/1758-2229.12190">https://doi.org/10.1111/1758-2229.12190</a>.
  ieee: K. Mitosch and M. T. Bollenbach, “Bacterial responses to antibiotics and their
    combinations,” <i>Environmental Microbiology Reports</i>, vol. 6, no. 6. Wiley,
    pp. 545–557, 2014.
  ista: Mitosch K, Bollenbach MT. 2014. Bacterial responses to antibiotics and their
    combinations. Environmental Microbiology Reports. 6(6), 545–557.
  mla: Mitosch, Karin, and Mark Tobias Bollenbach. “Bacterial Responses to Antibiotics
    and Their Combinations.” <i>Environmental Microbiology Reports</i>, vol. 6, no.
    6, Wiley, 2014, pp. 545–57, doi:<a href="https://doi.org/10.1111/1758-2229.12190">10.1111/1758-2229.12190</a>.
  short: K. Mitosch, M.T. Bollenbach, Environmental Microbiology Reports 6 (2014)
    545–557.
date_created: 2018-12-11T11:55:08Z
date_published: 2014-06-22T00:00:00Z
date_updated: 2023-09-07T12:00:25Z
day: '22'
department:
- _id: ToBo
doi: 10.1111/1758-2229.12190
ec_funded: 1
intvolume: '         6'
issue: '6'
language:
- iso: eng
month: '06'
oa_version: None
page: 545 - 557
project:
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
  grant_number: RGP0042/2013
  name: Revealing the fundamental limits of cell growth
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '303507'
  name: Optimality principles in responses to antibiotics
publication: Environmental Microbiology Reports
publication_status: published
publisher: Wiley
publist_id: '5076'
quality_controlled: '1'
related_material:
  record:
  - id: '818'
    relation: dissertation_contains
    status: public
scopus_import: 1
status: public
title: Bacterial responses to antibiotics and their combinations
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2014'
...
