Exploration of the TPP riboswitch as a new target for antibiotics
Therapeutics
- Ruth Brenk, University of Bergen, Norway (Coordinator)
- Petr Bartunek, Institute of Molecular Genetics of the ASCR, Czech Republic (Partner)
- Matthias Mack, Mannheim University of Applied Sciences, Germany (Partner)
- Gints Smits, Latvian Institute of Organic Synthesis, Latvia (Partner)
- Daniel Lafontaine, Université de Sherbrooke, Canada (Observer)
The antibiotics we are currently using are losing effectiveness due to the emergence of resistant bacteria. Therefore, there is an urgent need to develop new antibiotics. In this project, we aim to develop ligands for an RNA element (a so-called riboswitch), that controls the expression of essential bacterial genes. These ligands can then serve as starting points for drug discovery for future antibiotics. To reach this goal, we have assembled a team of highly skilled researchers from Norway, the Czech Republic, Latvia, Germany, and Canada. Together, we are developing a test system so that we can screen thousands of molecules for binding to the target. Subsequently, the identified ligands will be optimized to increase their affinity. The advanced compounds will be evaluated for antibiotic activity against the key bacteria for which new antibiotics are urgently needed. We will also carry out mode-of-action-studies to ensure that the compounds act on target as intended. If investigated riboswitch holds up to its high promises, this project will pave the way for urgently needed new antibiotics.
