---
res:
  bibo_abstract:
  - Combining drugs can improve the efficacy of treatments. However, predicting the
    effect of drug combinations is still challenging. The combined potency of drugs
    determines the drug interaction, which is classified as synergistic, additive,
    antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
    there is currently no biophysical model that can predict antibiotic interactions.
    Here, we present a physiologically relevant model of the combined action of antibiotics
    that inhibit protein synthesis by targeting the ribosome. This model captures
    the kinetics of antibiotic binding and transport, and uses bacterial growth laws
    to predict growth in the presence of antibiotic combinations. We find that this
    biophysical model can produce all drug interaction types except suppression. We
    show analytically that antibiotics which cannot bind to the ribosome simultaneously
    generally act as substitutes for one another, leading to additive drug interactions.
    Previously proposed null expectations for higher-order drug interactions follow
    as a limiting case of our model. We further extend the model to include the effects
    of direct physical or allosteric interactions between individual drugs on the
    ribosome. Notably, such direct interactions profoundly change the combined drug
    effect, depending on the kinetic parameters of the drugs used. The model makes
    additional predictions for the effects of resistance genes on drug interactions
    and for interactions between ribosome-targeting antibiotics and antibiotics with
    other targets. These findings enhance our understanding of the interplay between
    drug action and cell physiology and are a key step toward a general framework
    for predicting drug interactions.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Bor
      foaf_name: Kavcic, Bor
      foaf_surname: Kavcic
      foaf_workInfoHomepage: http://www.librecat.org/personId=350F91D2-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0001-6041-254X
  - foaf_Person:
      foaf_givenName: Gašper
      foaf_name: Tkačik, Gašper
      foaf_surname: Tkačik
      foaf_workInfoHomepage: http://www.librecat.org/personId=3D494DCA-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0002-6699-1455
  - foaf_Person:
      foaf_givenName: Tobias
      foaf_name: Bollenbach, Tobias
      foaf_surname: Bollenbach
      foaf_workInfoHomepage: http://www.librecat.org/personId=3E6DB97A-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0003-4398-476X
  bibo_doi: 10.1101/2020.04.18.047886
  dct_date: 2020^xs_gYear
  dct_language: eng
  dct_title: A minimal biophysical model of combined antibiotic action@
...