001043185 001__ 1043185
001043185 005__ 20250818202300.0
001043185 0247_ $$2datacite_doi$$a10.34734/FZJ-2025-02793
001043185 0247_ $$2URN$$aurn:nbn:de:0001-2508181047006.380374208525
001043185 037__ $$aFZJ-2025-02793
001043185 1001_ $$0P:(DE-Juel1)190617$$aRackow, Bente$$b0$$ufzj
001043185 245__ $$aElucidation of anti-viral strategies in Streptomyces$$f- 2025-06-12
001043185 260__ $$aJülich$$bForschungszentrum Jülich GmbH Zentralbibliothek, Verlag$$c2025
001043185 300__ $$axii, 148
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001043185 3367_ $$2DRIVER$$adoctoralThesis
001043185 4900_ $$aSchriften des Forschungszentrums Jülich Reihe Schlüsseltechnologien / Key Technologies$$v298
001043185 502__ $$aDissertation, Düsseldorf, 2025$$bDissertation$$cDüsseldorf$$d2025
001043185 520__ $$aStreptomyces 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.
001043185 536__ $$0G:(DE-HGF)POF4-2171$$a2171 - Biological and environmental resources for sustainable use (POF4-217)$$cPOF4-217$$fPOF IV$$x0
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001043185 9141_ $$y2025
001043185 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)190617$$aForschungszentrum Jülich$$b0$$kFZJ
001043185 9131_ $$0G:(DE-HGF)POF4-217$$1G:(DE-HGF)POF4-210$$2G:(DE-HGF)POF4-200$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-2171$$aDE-HGF$$bForschungsbereich Erde und Umwelt$$lErde im Wandel – Unsere Zukunft nachhaltig gestalten$$vFür eine nachhaltige Bio-Ökonomie – von Ressourcen zu Produkten$$x0
001043185 920__ $$lyes
001043185 9201_ $$0I:(DE-Juel1)IBG-1-20101118$$kIBG-1$$lBiotechnologie$$x0
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