Dokument: The anti-tubercular callyaerins target the Mycobacterium tuberculosis-specific non-essential membrane protein Rv2113
| Titel: | The anti-tubercular callyaerins target the Mycobacterium tuberculosis-specific non-essential membrane protein Rv2113 | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67649 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241122-104458-9 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Podlesainski, David [Autor] Adeniyi, Emmanuel T. [Autor] Gröner, Yvonne [Autor] Schulz, Florian [Autor] Krisilia, Violetta [Autor] Rehberg, Nidja [Autor] Richter, Tim [Autor] Sehr, Daria [Autor] Xie, Huzhuyue [Autor] Simons, Viktor E. [Autor] | |||||||
| Dateien: |
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| Stichwörter: | natural product, photoaffinity labeling, callyaerin, Mycobacterium tuberculosis, antibiotic action, anti-TB drug development, cyclopeptide | |||||||
| Beschreibung: | Spread of antimicrobial resistances urges a need for new drugs against Mycobacterium tuberculosis (Mtb) with mechanisms differing from current antibiotics. Previously, callyaerins were identified as promising anti-tubercular agents, representing a class of hydrophobic cyclopeptides with an unusual (Z)-2,3-di-aminoacrylamide unit. Here, we investigated the molecular mechanisms underlying their antimycobacterial properties. Structure-activity relationship studies enabled the identification of structural determinants relevant for antibacterial activity. Callyaerins are bacteriostatics selectively active against Mtb, including extensively drug-resistant strains, with minimal cytotoxicity against human cells and promising intracellular activity. By combining mutant screens and various chemical proteomics approaches, we showed that callyaerins target the non-essential, Mtb-specific membrane protein Rv2113, triggering a complex dysregulation of the proteome, characterized by global downregulation of lipid biosynthesis, cell division, DNA repair, and replication. Our study thus identifies Rv2113 as a previously undescribed Mtb-specific drug target and demonstrates that also non-essential proteins may represent efficacious targets for antimycobacterial drugs. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Podlesainski, D., Adeniyi, E. T., Gröner, Y., Schulz, F., Krisilia, V., Rehberg, N., Richter, T., Sehr, D., Xie, H., Simons, V. E., Kiffe-Delf, A.-L. I. R., Kaschani, F., Ioerger, T. R., Kaiser, M., & Kalscheuer, R. (2024). The anti-tubercular callyaerins target the Mycobacterium tuberculosis-specific non-essential membrane protein Rv2113. Cell Chemical Biology, 31(10), 1755-1771.e73. https://doi.org/10.1016/j.chembiol.2024.06.002 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 22.11.2024 | |||||||
| Dateien geändert am: | 22.11.2024 |
