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@PHDTHESIS{Rackow:1043185,
      author       = {Rackow, Bente},
      title        = {{E}lucidation of anti-viral strategies in {S}treptomyces},
      volume       = {298},
      school       = {Düsseldorf},
      type         = {Dissertation},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {FZJ-2025-02793},
      series       = {Schriften des Forschungszentrums Jülich Reihe
                      Schlüsseltechnologien / Key Technologies},
      pages        = {xii, 148},
      year         = {2025},
      note         = {Dissertation, Düsseldorf, 2025},
      abstract     = {Streptomyces species have been highly studied for decades
                      for their multicellular development and their distinguished
                      ability to produce a myriad of different bioactive small
                      molecules. In recent years the interaction between these
                      multicellular bacteria and their predatory viruses, the
                      bacteriophages (or phages for short) came into the focus of
                      research. It was recently discovered that specialized
                      metabolites produced by Streptomyces not only protect from
                      competing bacteria but also from phage infections. Both
                      aminoglycosides and anthracyclines, small molecules produced
                      by Streptomyces have been shown to efficiently inhibit phage
                      infection, but the exact mechanism of action remained
                      elusive. This multi functionality of small molecules piqued
                      the interest. This work sets out to elucidate suchanti-viral
                      strategies of Streptomyces and to integrate the chemical
                      defense mediated by small molecules into the context of the
                      bacterial immune system. Initially, spent medium of natural
                      aminoglycoside producing Streptomyces spp. was tested for
                      its antiphagepotential, showing different degrees of defense
                      potential, specific to the molecule produced as well as the
                      phage tested. Extracellular effects of spent medium could
                      only be determined for phages infecting less related
                      species, such as Corynebacterium glutamicum. Furthermore,
                      isolation and characterization of novel Streptomyces phages
                      broadened the repertoire of phages that can be used to
                      understand the interaction between host and phage and how
                      chemical defense affects this interaction. Three of the four
                      newly isolated phages infect several different species.
                      These broad host range phages pose to be good tools to
                      understand also the influence of the host background on the
                      efficiency of chemical defense. Large screenings of small
                      molecules mediating chemical defense with two different
                      collections of phages revealed several sensitivity
                      determinants of phages to chemical defense and showed that
                      the efficiency of chemical defense is a delicate process
                      influenced by a manifold of factors. Streptomyces phages
                      showed sensitivity towards most of the compounds tested,
                      whereas coliphages only showed sensitivity towards DNA
                      intercalating molecules. Redirecting the focus of this work
                      towards the mechanism of action of the anthracycline
                      daunorubicin, many insights in the inhibitory effect of this
                      small molecule were obtained. Daunorubicin acts
                      intracellularly, after the genome injection of phages but
                      before DNA replication. The host background influences the
                      potency of daunorubicin-mediated defense and synergy between
                      chemical defense and intracellular defense systems could
                      bedetermined. Even though the direct mechanism of action of
                      chemical defense remains yet elusive, several important
                      insights were gained and provide basis for further research
                      in this area of anti-phage defense.},
      cin          = {IBG-1},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2171 - Biological and environmental resources for
                      sustainable use (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2171},
      typ          = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:0001-2508181047006.380374208525},
      doi          = {10.34734/FZJ-2025-02793},
      url          = {https://juser.fz-juelich.de/record/1043185},
}