---
res:
  bibo_abstract:
  - '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.@eng'
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Andreas
      foaf_name: Angermayr, Andreas
      foaf_surname: Angermayr
      foaf_workInfoHomepage: http://www.librecat.org/personId=4677C796-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0001-8619-2223
  - foaf_Person:
      foaf_givenName: Tin Yau
      foaf_name: Pang, Tin Yau
      foaf_surname: Pang
  - foaf_Person:
      foaf_givenName: Guillaume
      foaf_name: Chevereau, Guillaume
      foaf_surname: Chevereau
  - foaf_Person:
      foaf_givenName: Karin
      foaf_name: Mitosch, Karin
      foaf_surname: Mitosch
      foaf_workInfoHomepage: http://www.librecat.org/personId=39B66846-F248-11E8-B48F-1D18A9856A87
  - foaf_Person:
      foaf_givenName: Martin J
      foaf_name: Lercher, Martin J
      foaf_surname: Lercher
  - foaf_Person:
      foaf_givenName: Mark Tobias
      foaf_name: Bollenbach, Mark Tobias
      foaf_surname: Bollenbach
      foaf_workInfoHomepage: http://www.librecat.org/personId=3E6DB97A-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0003-4398-476X
  bibo_doi: 10.15252/msb.202110490
  bibo_issue: '9'
  bibo_volume: 18
  dct_date: 2022^xs_gYear
  dct_identifier:
  - UT:000856482800001
  dct_isPartOf:
  - http://id.crossref.org/issn/1744-4292
  dct_language: eng
  dct_publisher: Embo Press@
  dct_subject:
  - Applied Mathematics
  - Computational Theory and Mathematics
  - General Agricultural and Biological Sciences
  - General Immunology and Microbiology
  - General Biochemistry
  - Genetics and Molecular Biology
  - Information Systems
  dct_title: Growth‐mediated negative feedback shapes quantitative antibiotic response@
  fabio_hasPubmedId: '36124745'
...