TY  - THES
AU  - Rackow, Bente
TI  - Elucidation of anti-viral strategies in Streptomyces
VL  - 298
PB  - Düsseldorf
VL  - Dissertation
CY  - Jülich
M1  - FZJ-2025-02793
T2  - Schriften des Forschungszentrums Jülich Reihe Schlüsseltechnologien / Key Technologies
SP  - xii, 148
PY  - 2025
N1  - Dissertation, Düsseldorf, 2025
AB  - 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.
LB  - PUB:(DE-HGF)3 ; PUB:(DE-HGF)11
DO  - DOI:10.34734/FZJ-2025-02793
UR  - https://juser.fz-juelich.de/record/1043185
ER  -