Project Details
Projekt
Integration of multicellular defense strategies in the context of the bacterial immune system
Applicant
Professorin Dr. Julia Frunzke
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Microbial Ecology and Applied Microbiology
Microbial Ecology and Applied Microbiology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 464434020
The last few years provided unprecedented insights into the complexity of prokaryotic antiviral immune systems. This also extends to antiviral strategies acting at the multicellular level such as the secretion of antiphage molecules produced by bacteria, the release of membrane vesicles or the development of transient phage resistance. In the first funding period of SPP 2330, we could show that aminoglycoside antibiotics, produced by Streptomyces, inhibit infection by a broad range of phages by blocking an early stage in the viral life cycle. This effect was also shown using spent medium of the natural producer of the aminoglycoside apramycin (Streptoalloteichus tenebrarius) underscoring the physiological relevance of this phenomenon. Further, we could show that typical mechanisms conferring resistance to aminoglycoside antibiotics, such as drug or target site modifications, abolish the antibacterial properties of the compounds, but do not interfere with the antiviral properties. These findings strongly suggest that the targets for the antibacterial and antiphage function are distinct. Studying phage infection in Streptomyces, featuring a multicellular life style, we further observed that phage infection triggers the formation of transiently phage-resistant mycelium at the infection interface and could show that this cellular development is crucial for the containment of viral infections. In the proposed project, we will build on these previous findings by focusing on the identification of phage determinants conferring sensitivity to antiphage molecules and examining the impact of phage epigenomic modifications. We will address the impact of phage infection on cellular development and will investigate the potential role of amyloid surface proteins (rodlins and chaplins) in the emergence of transient resistance. Further, we will unravel the role of phage-encoded WhiB-like proteins, which belong to the most abundant regulators in phages infecting actinobacteria, in the modulation of host responses. Finally and importantly, we aim at an integration of multicellular defense strategies in the context of the bacterial immune system by unraveling potential synergistic interactions with other defense systems. Overall, we expect that the outcomes of this project will extend our comprehension of multicellular defense strategies, offering a more holistic perspective on prokaryotic antiviral immunity.
DFG Programme
Priority Programmes
