Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gubensäk, N; Sagmeister, T; Buhlheller, C; Geronimo, BD; Wagner, GE; Petrowitsch, L; Gräwert, MA; Rotzinger, M; Berger, TMI; Schäfer, J; Usón, I; Reidl, J; Sánchez-Murcia, PA; Zangger, K; Pavkov-Keller, T.
Vibrio cholerae's ToxRS bile sensing system.
Elife. 2023; 12:
Doi: 10.7554/eLife.88721
[OPEN ACCESS]
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Gubensäk Nina Kerstin
- Co-Autor*innen der Med Uni Graz
- Buhlheller Christoph
- Di Geronimo Quintero Bruno
- Sánchez Murcia Pedro Alejandro
- Wagner-Lichtenegger Gabriel
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- Abstract:
- The seventh pandemic of the diarrheal cholera disease, which began in 1960, is caused by the Gram-negative bacterium Vibrio cholerae. Its environmental persistence provoking recurring sudden outbreaks is enabled by V. cholerae's rapid adaption to changing environments involving sensory proteins like ToxR and ToxS. Located at the inner membrane, ToxR and ToxS react to environmental stimuli like bile acid, thereby inducing survival strategies for example bile resistance and virulence regulation. The presented crystal structure of the sensory domains of ToxR and ToxS in combination with multiple bile acid interaction studies, reveals that a bile binding pocket of ToxS is only properly folded upon binding to ToxR. Our data proposes an interdependent functionality between ToxR transcriptional activity and ToxS sensory function. These findings support the previously suggested link between ToxRS and VtrAC-like co-component systems. Besides VtrAC, ToxRS is now the only experimentally determined structure within this recently defined superfamily, further emphasizing its significance. In-depth analysis of the ToxRS complex reveals its remarkable conservation across various Vibrio species, underlining the significance of conserved residues in the ToxS barrel and the more diverse ToxR sensory domain. Unravelling the intricate mechanisms governing ToxRS's environmental sensing capabilities, provides a promising tool for disruption of this vital interaction, ultimately inhibiting Vibrio's survival and virulence. Our findings hold far-reaching implications for all Vibrio strains that rely on the ToxRS system as a shared sensory cornerstone for adapting to their surroundings.
- Find related publications in this database (using NLM MeSH Indexing)
- Transcription Factors - metabolism
- DNA-Binding Proteins - metabolism
- Bacterial Proteins - metabolism
- Bile - metabolism
- Vibrio - administration & dosage
- Vibrio cholerae - metabolism
- Bile Acids and Salts - metabolism
- Gene Expression Regulation, Bacterial - administration & dosage
- Find related publications in this database (Keywords)
- Vibrio cholerae
- protein interaction
- virulence regulation
- transcription factor
- sensory proteins
- ToxRS
- Other