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| Home > Publications database > Regulatory interactions between $\textit{Corynebacterium glutamicum}$ and its prophages |
| Home > Publications database > Regulatory interactions between $\textit{Corynebacterium glutamicum}$ and its prophages |
| Book/Dissertation / PhD Thesis | FZJ-2020-00297 |
2019
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
ISBN: 978-3-95806-445-4
Please use a persistent id in citations: http://hdl.handle.net/2128/24069 urn:nbn:de:0001-2020012905
Abstract: Viruses preying on bacteria, so‐called bacteriophages, are significantly involved in shaping the evolution of microorganisms. More than 1031 phage virions are involved in the transduction of an estimated number of 1025 ‐ 1028 base pairs of DNA, already in the marine environment. Consequently, it is not surprising that viral DNA represents a major cause for strain‐specific differences within bacterial species. In around 46 % of genomes of all completely sequenced bacteria, at least one active prophage elementcould be identified, whereas the number of cryptic prophage elements is expected to be even higher. The integration of virus‐derived DNA material (e.g. in the form of prophages) into the host genome involves the risk of toxic gene products and thus requires stringent regulation. However, the presence of these prophages not only bears risks for the host cell but also may encode potential beneficial traits for the recipient cell. To gain an adaptive advantage from newly acquired DNA, successful integrationinto host regulatory circuits is mandatory.
Viruses preying on bacteria, so‐called bacteriophages, are significantly involved in shaping the evolution of microorganisms. More than 10$^{31}$ phage virions are involved in the transduction of an estimated number of 10$^{25}$ ‐ 10$^{28}$ base pairs of DNA, already in the marine environment. Consequently, it is not surprising that viral DNA represents a major cause for strain‐specific differences within bacterial species. In around 46 % of genomes of all completely sequenced bacteria, at least one active prophage element could be identified, whereas the number of cryptic prophage elements is expected to be even higher. The integration of virus‐derived DNA material (e.g. in the form of prophages) into the host genome involves the risk of toxic gene products and thus requires stringent regulation. However, the presence of these prophages not only bears risks for the host cell but also may encode potential beneficial traits for the recipient cell. To gain an adaptive advantage from newly acquired DNA, successful integration into host regulatory circuits is mandatory. The actinobacterial strain $\textit{C. glutamicum}$ ATCC 13032 contains a total of four prophage elements (CGP1‐ 4). The inducible CGP3 prophage covers nearly 7 % (~219 kbp) of the entire $\textit{C. glutamicum}$ genome and contains the prophage element CGP4. Previous studies revealed that CGP3 is spontaneously induced in a small fraction of cells and can be triggered in an SOS‐dependent manner. Recently, we identified the Lsr2‐like protein CgpS as an essential xenogeneic silencer of the cryptic prophages in $\textit{C. glutamicum}$. This thesis aimed at shedding light on how CgpS is governing the lysogenic state of CGP3 and studying the regulatory interaction between the host and the prophage. Chromatin affinity purification and sequencing (ChAP‐Seq) revealed a redistribution of CgpS under prophage‐inducing conditions towards different targets in the host genome coinciding with a lower coverage at the prophage region. Under prophage‐inducing conditions, CgpS binds to multiple host targets, comprising genes with important functions in DNA replication and repair mechanisms, cell envelope biosynthesis and global transcriptional regulators. While previous approaches relied on a snapshot view of XS binding, these data present the first time‐resolved analysis of XS protein binding behavior under prophage‐inducing conditions. Furthermore, the regulatory interactions between host‐encoded regulators and the CGP3 prophage were studied. DNA affinity chromatographies with different CGP3 promoters as well as global binding profile analyses of different $\textit{C. glutamicum}$ regulators revealed that several host regulators bind inside of the CGP3 region. One of these regulators, the MarR‐type regulator MalR, was a subject of further studies. Regulators of the MarR‐type family have been shown to be involved in environmental stress responses, regulation of virulence genes, and degradation of aromatic compounds. Furthermore, different studies showed that MarR‐type regulators are involved in the counter‐silencing of H‐NS silenced horizontally acquired genes in $\textit{Escherichia coli}$ and $\textit{Salmonella enterica}$. A combination of ChAPseq based binding profiling and transcriptome analysis using DNA microarrays revealed the function of MalR as a regulator involved in the stress‐responsive remodeling of the cell envelope of $\textit{C. glutamicum}$ with several binding sites inside of CGP3. A malR deletion strain showed higher sensitivity towards different $\beta$‐lactam antibiotics, and overexpression of $\textit{malR}$ led to a significantly altered cell envelope. Increased levels of MalR impaired inducibility of the CGP3 prophage, indicating a link between the regulation of cell envelope composition and prophage induction. Overall, this thesis provides valuable insights into the dynamic binding behavior of the XS protein CgpS under prophage‐inducing conditions and reveals a high degree of regulatory interaction between host regulators and the CGP3 prophage in $\textit{C. glutamicum}$.
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