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Activation of the glmS Ribozyme Confers Bacterial Growth Inhibition |
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| Authors: | Anna Schüller Daniel Matzner Dr. Christina E. Lünse Prof. Dr. Valentin Wittmann Dr. Catherine Schumacher Sandra Unsleber Prof. Dr. Heike Brötz‐Oesterhelt Prof. Dr. Christoph Mayer Prof. Dr. Gabriele Bierbaum Prof. Dr. Günter Mayer |
| Affiliation: | 1. University of Bonn, LIMES Institute, Bonn, Germany;2. University of Leipzig, Institute for Biochemistry, Leipzig, Germany;3. University of Konstanz, Chemistry Department, Konstanz, Germany;4. University of Düsseldorf, Institute for Pharmaceutical Biology, Düsseldorf, Germany;5. University of Tübingen, Interfaculty Institute for Microbiology and Infection Medicine, Department of Microbiology & Biotechnology, Auf der Morgenstelle 28, Tübingen, Germany;6. University of Tübingen, Interfaculty Institute for Microbiology and Infection Medicine, Department of Microbial Bioactive Compounds, Auf der Morgenstelle 28, Tübingen, Germany;7. University of Bonn, Institute of Medical Microbiology, Immunology and Parasitology, Bonn, Germany |
| Abstract: | The ever‐growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as‐yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba‐α‐d ‐glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN‐mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self‐cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism. |
| Keywords: | antibiotics hydrolysis ribozymes RNA |