Dokument: The role of cellular development in multicellular antiphage defense of Streptomyces
| Titel: | The role of cellular development in multicellular antiphage defense of Streptomyces | |||||||
| Weiterer Titel: | Die Rolle der zellulären Entwicklung bei der multizellulären Phagenabwehr von Streptomyces | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=66209 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20240715-145126-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Luthe, Tom [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Frunzke, Julia [Gutachter] Prof. Dr. Wierckx, Nick [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Bacteriophages, the viruses of bacteria, are ubiquitously found and represent the most abundant biological entities on the planet. Phage predation poses a constant threat to bacterial communities and results in an ongoing arms race characterized by continuous adaptation and counter-adaptation. In order to promote their survival and distribution, soil bacteria like Streptomyces developed diverse strategies including key features of filamentous, multicellular growth and a multifaceted secondary metabolite production.
This doctoral thesis focused on the impact of cellular development on phage infection during the multicellular life cycle of Streptomyces. We observed enhanced differentiation of interface mycelium directly surrounding the lysis zones of diverse phage-host pairs. Interestingly, this differentiation was accompanied by development-dependent growing and shrinking dynamics, which revealed the emergence of transiently resistant mycelial structures crucial for the containment of viral infections. This transient resistance is provided by the developmental cell surface changes that render the cells less susceptible to phage infection and enable regrowth into the lysis zone. This was additionally shown by a reduced adsorption of phage particles to older mycelium and non-growing spores. Transcriptome analysis revealed that phage infection triggers an upregulation of chloramphenicol biosynthesis genes, which could have a role in communicating ongoing infection to neighboring cells. Direct antiphage effects were not observed for the phages tested in this study. Moreover, during early infection, these data showed downregulation of chaplin and rodlin genes as well as almost all whi genes involved in sporulation. This could facilitate phage propagation and may be actively induced by the phage. Bioinformatic analysis of phage genomes revealed the Actinobacteria-specific family of WhiB-like proteins as most abundant transcriptional regulators in actinobacteriophages. In the Streptomyces host, WhiB-like proteins are involved in differentiation, sporulation and antibiotic resistance. While we found WhiB-like regulators to be encoded by 32% of all analyzed Streptomyces phages, almost 90% of these phages were categorized as virulent. In addition to WhiB, especially FtsK and ParB-like proteins relevant to sporulation processes are encoded by smaller subsets of bacteriophages infecting Streptomyces. The diverse WhiB-like regulators encoded by Streptomyces phages both share conserved features of their host counterparts and have modified domains, which potentially mediate distinct functionalities. To further elucidate the role of these regulators, we used complementation and overexpression assays with a set of diverse phage-encoded WhiB-like proteins in S. venezuelae. Intriguingly, none of the phage genes restored the sporulation phenotype in a host whiB deletion strain. However, constitutive expression of phage whiB genes in the wild-type strain revealed multiple changes in cellular development. Chymera-encoded WhiB resulted in accelerated sporulation, whereas unbranched hyphal elongation and a delay of differentiation was caused by expression of whiB originating from Alderaan and Coruscant. These changes also influence efficacy of phage propagation. Taken together, the results of this thesis emphasize multicellular development as a key feature in phage-host interactions in Streptomyces. The work presented highlights the importance of transient phage resistance as an essential layer of Streptomyces antiviral immunity. It further implies the potential engagement of phage proteins in interfering with the regulatory network governing cellular development, thereby improving phage propagation. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Sonstige Einrichtungen/Externe » Institute in Zusammenarbeit mit der Heinrich-Heine-Universität Düsseldorf » Institut für Biotechnologie, Forschungszentrum Jülich GmbH | |||||||
| Dokument erstellt am: | 15.07.2024 | |||||||
| Dateien geändert am: | 15.07.2024 | |||||||
| Promotionsantrag am: | 19.12.2023 | |||||||
| Datum der Promotion: | 22.04.2024 |
