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@ARTICLE{Klnemann:170558,
      author       = {M. Klünemann and S. Andrejev$^*$ and S. Blasche and A.
                      Mateus and P. Phapale and S. Devendran and J. Vappiani and
                      B. Simon and T. A. Scott and E. Kafkia and D. Konstantinidis
                      and K. Zirngibl and E. Mastrorilli and M. Banzhaf and M.-T.
                      Mackmull and F. Hövelmann and L. Nesme and A. R. Brochado
                      and L. Maier and T. Bock and V. Periwal and M. Kumar and Y.
                      Kim and M. Tramontano and C. Schultz and M. Beck and J.
                      Hennig and M. Zimmermann and D. C. Sévin and F. Cabreiro
                      and M. M. Savitski and P. Bork and A. Typas and K. R. Patil},
      title        = {{B}ioaccumulation of therapeutic drugs by human gut
                      bacteria.},
      journal      = {Nature},
      volume       = {597},
      number       = {7877},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2021-02009},
      pages        = {533-538},
      year         = {2021},
      note         = {#EA:B400# /2021 Sep;597(7877):533-538},
      abstract     = {Bacteria in the gut can modulate the availability and
                      efficacy of therapeutic drugs. However, the systematic
                      mapping of the interactions between drugs and bacteria has
                      only started recently1 and the main underlying mechanism
                      proposed is the chemical transformation of drugs by
                      microorganisms (biotransformation). Here we investigated the
                      depletion of 15 structurally diverse drugs by 25
                      representative strains of gut bacteria. This revealed 70
                      bacteria-drug interactions, 29 of which had not to our
                      knowledge been reported before. Over half of the new
                      interactions can be ascribed to bioaccumulation; that is,
                      bacteria storing the drug intracellularly without chemically
                      modifying it, and in most cases without the growth of the
                      bacteria being affected. As a case in point, we studied the
                      molecular basis of bioaccumulation of the widely used
                      antidepressant duloxetine by using click chemistry, thermal
                      proteome profiling and metabolomics. We find that duloxetine
                      binds to several metabolic enzymes and changes the
                      metabolite secretion of the respective bacteria. When tested
                      in a defined microbial community of accumulators and
                      non-accumulators, duloxetine markedly altered the
                      composition of the community through metabolic
                      cross-feeding. We further validated our findings in an
                      animal model, showing that bioaccumulating bacteria
                      attenuate the behavioural response of Caenorhabditis elegans
                      to duloxetine. Together, our results show that
                      bioaccumulation by gut bacteria may be a common mechanism
                      that alters drug availability and bacterial metabolism, with
                      implications for microbiota composition, pharmacokinetics,
                      side effects and drug responses, probably in an individual
                      manner.},
      cin          = {B400},
      ddc          = {500},
      cid          = {I:(DE-He78)B400-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34497420},
      doi          = {10.1038/s41586-021-03891-8},
      url          = {https://inrepo02.dkfz.de/record/170558},
}