Vibrio cholerae's ToxRS bile sensing system
- University of Graz, Austria
- Medical University of Graz, Austria
- EMBL Hamburg, Germany
- RedShiftBio, United States
- Institute of Molecular Biology, Spain
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 e.g. 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.
Data availability
- Diffraction data have been deposited in PDB under the accession code 8ALO-SAXS data have been deposited:ToxR - SASDR25https://www.sasbdb.org/data/SASDR25/x14svn58xr/ToxS - SASDR35https://www.sasbdb.org/data/SASDR35/ti6yxfu94f/ToxR:ToxS -SASDR45https://www.sasbdb.org/data/SASDR45/8t9oq6fvvj/ToxR:ToxS:bile - SASDR55https://www.sasbdb.org/data/SASDR55/1f1om17ki6/- All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
Author details
Funding
Austrian Science Fund (FWF T-1239)
- Nina Gubensäk
Austrian Science Fund (FWF DK W09)
- Klaus Zangger
Austrian Science Fund (FWF P 29405)
- Joachim Reidl
Land Steiermark (1109)
- Klaus Zangger
Spanish MICINN/AEI/FEDER/UE (PID2021-128751NB-I00)
- Isabel Usón
Austrian Science Fund (Biomolecular Structures and Interactions DOC 130)
- Tea Pavkov-Keller
Austrian Science Fund (Molecular Metabolism DOC 50)
- Theo Sagmeister
Fundación Martínez Escudero
- Bruno Di Geronimo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Gubensäk et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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