Final Report Summary - RNANTIBIOTICS (RNA-mediated virulence gene regulation: Identification of novel antibacterial compounds)
This Project was based on two main parts, RNA-Biology and bacterial stress-regulation in the Gram-positive bacterial pathogen L. moncytogenes. For the RNA-biology part, we have focused on 4 sub-projects. 1. prfA-regulation. Expression of the virulence regulator PrfA is controlled by two RNA-mediated mechanisms: a thermosensor located in front of the structural mRNA and a trans-acting RNA element. In this Project, we also found that the 5-part of the structural mRNA is required to be maintained in a non-structural conformation to allow maximal virulence gene expression. 2. Rli38. Previously, we have identified a small regulatory RNA (Rli38) being massively induced during Listeria exposure to human blood and important for bacterial infection. We have now identified putative binding partners to Rli38 through 2D-gel/mass-spectrometry and transcriptome analysis. In Connection to this, we also examined and cerified the chicken embryo as a suitable model for studying Listeria infection. 3. Function of 5' UTRs. We have also in more detail examined the function of 5'-untranslated RNAs (UTRs) located in front of different mRNAs and been able to identify mechanisms by how these are controlled. In particular, we have identified an antisense RNA mechanism able to block expression of a regulator at specific metabolite conditions. 4. RNA-helicases. A large part of the ERC-Project has been devoted to identifying the function of RNA-helicases during bacterial physiology and virulence. We have identified particular functions of different RNA-helicases at certain conditions.
For the second part of the Project, bacterial stress-regulation, we unexpectedly identified cycles of light and dark to coordinate bacterial development through a blue-light receptor. We found that the sensing of light triggered a very complex response involving the stress-sigma factor, sigmaB and a protein complex known as the "stressosome".
For the second part of the Project, bacterial stress-regulation, we unexpectedly identified cycles of light and dark to coordinate bacterial development through a blue-light receptor. We found that the sensing of light triggered a very complex response involving the stress-sigma factor, sigmaB and a protein complex known as the "stressosome".