Molecular mechanisms of a bacterial dynamin-like protein in phage defense

• Applicant: Professor Dr. Marc Bramkamp
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Biochemistry ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539937824

Bacteria are exposed to a myriad of different environmental stresses, with phage predation playing a dominant role. Consequently, they have evolved mechanisms to counteract these stresses and ensure survival. We have recently identified a bacterial dynamin-like protein, DynA from Bacillus subtilis that is involved in phage resistance. Strains lacking dynA are highly sensitive to phage infection. In vitro analysis using sophisticated lipid-mixing and content-mixing assays we show that DynA is able to tether and fuse membranes in trans. High resolution imaging shows that DynA is highly dynamic on the membrane, but forms stable protein cluster during stress, likely at the sites of membrane lesions. Phage infection assays reveal that DynA likely does not interfere with phage replication, but may prevent efficient release of phage progeny. This slows down the spreading of the infection in bacterial communities. Bacterial dynamins thus part of the bacterial immune system. We now aim at the understanding of how DynA works at the membrane during phage mediated cell lysis. Specifically, we will use superresolution microscopy and structural analysis to unravel the mechanims by which DynA delays host cell lysis. Nucleotide hydrolysis and membrane binding of DynA are required for the anti-phage effect, suggesting that a power-stroke mechanism might fuse membrane pores.

• DFG Programme: Research Grants