Graduate Students Mini Symposium VII - 2026

13:15 h Sara Jakob - AG Thanbichler
The virulence regulator VirB from Shigella flexneri uses a CTP-dependent switch mechanism to activate gene expression

The second leading cause of diarrheal mortality is bacterial dysentery caused by Shigella spp. Shigella invades the epithelial lining of the intestinal tract and causes watery diarrhea. The temperature upshift to human body temperature leads to a regulatory cascade that induces a number of genes on a large 220 kb virulence plasmid. Previous studies of S. flexneri have shown that an unconventional transcription regulator, VirB, is required for pathogenesis. Its production depends on temperature induced synthesis of the master regulator VirF, which in turn activates the expression of virB. In a host-free environment, the nucleoid-associated protein H-NS silences genes involved in virulence to ensure strict control and precise timing of the invasion. VirB acts as a transcriptional anti-silencer and activates virulence gene expression by counteracting H-NS in a virS-DNA dependent manner. In contrast to conventional transcriptional activators, VirB does not interact directly with the RNA polymerase, but interacts with (virS) sites far upstream of the target promoters. Notably, VirB belongs to the ParB family of proteins, which are known to form partition complexes to distribute the chromosomal DNA or low-copy plasmids between the two daughter cells. The newly discovered CTPase activity of ParB that allows its binding and sliding along the DNA raised the question of whether VirB uses a similar mode of action. Our recent data revealed that VirB indeed acts as a CTP-dependent molecular switch to activate gene expression of its target promoters. VirB loading and spreading on the virS site has been proposed to lead to a local decrease in negative supercoiling, thereby destabilizing H-NS to activate gene expression. To clarify the mechanism underlying this molecular anti-silencing, we further focused on how VirB and H-NS affect DNA topology and promoter accessibility. Moreover, advanced microscopy techniques provide new insights into the mechanistic principles of transcriptional anti-silencing of VirB and H-NS.

13:45 h Max Kilian - AG Bischofs-Pfeifer
Developmental regulation of forespore positioning in sporulating Bacillus subtilis cells