---
res:
  bibo_abstract:
  - Abstract Drug combinations are increasingly important in disease treatments, for
    combating drug resistance, and for elucidating fundamental relationships in cell
    physiology. When drugs are combined, their individual effects on cells may be
    amplified or weakened. Such drug interactions are crucial for treatment efficacy,
    but their underlying mechanisms remain largely unknown. To uncover the causes
    of drug interactions, we developed a systematic approach based on precise quantification
    of the individual and joint effects of antibiotics on growth of genome-wide Escherichia
    coli gene deletion strains. We found that drug interactions between antibiotics
    representing the main modes of action are highly robust to genetic perturbation.
    This robustness is encapsulated in a general principle of bacterial growth, which
    enables the quantitative prediction of mutant growth rates under drug combinations.
    Rare violations of this principle exposed recurring cellular functions controlling
    drug interactions. In particular, we found that polysaccharide and ATP synthesis
    control multiple drug interactions with previously unexplained mechanisms, and
    small molecule adjuvants targeting these functions synthetically reshape drug
    interactions in predictable ways. These results provide a new conceptual framework
    for the design of multidrug combinations and suggest that there are universal
    mechanisms at the heart of most drug interactions. Synopsis A general principle
    of bacterial growth enables the prediction of mutant growth rates under drug combinations.
    Rare violations of this principle expose cellular functions that control drug
    interactions and can be targeted by small molecules to alter drug interactions
    in predictable ways. Drug interactions between antibiotics are highly robust to
    genetic perturbations. A general principle of bacterial growth enables the prediction
    of mutant growth rates under drug combinations. Rare violations of this principle
    expose cellular functions that control drug interactions. Diverse drug interactions
    are controlled by recurring cellular functions, including LPS synthesis and ATP
    synthesis. A general principle of bacterial growth enables the prediction of mutant
    growth rates under drug combinations. Rare violations of this principle expose
    cellular functions that control drug interactions and can be targeted by small
    molecules to alter drug interactions in predictable ways.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Guillaume
      foaf_name: Chevereau, Guillaume
      foaf_surname: Chevereau
      foaf_workInfoHomepage: http://www.librecat.org/personId=424D78A0-F248-11E8-B48F-1D18A9856A87
  - 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.20156098
  bibo_issue: '4'
  bibo_volume: 11
  dct_date: 2015^xs_gYear
  dct_identifier:
  - UT:000354022300005
  dct_language: eng
  dct_publisher: Nature Publishing Group@
  dct_title: Systematic discovery of drug interaction mechanisms@
...