Vibrio cholerae's ToxRS bile sensing system.

Autor:	Gubensäk N; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Sagmeister T; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Buhlheller C; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Geronimo BD; Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Graz, Austria., Wagner GE; Institute of Chemistry / Organic and Bioorganic Chemistry, Medical University of Graz, Graz, Austria.; Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria., Petrowitsch L; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Gräwert MA; Biological Small Angle Scattering, EMBL Hamburg, Hamburg, Germany., Rotzinger M; Institute of Chemistry / Organic and Bioorganic Chemistry, Medical University of Graz, Graz, Austria., Berger TMI; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Schäfer J; RedShiftBio, Boxborough, United States., Usón I; Institute of Molecular Biology of Barcelona, Barcelona, Spain.; ICREA, Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain., Reidl J; Institute of Molecular Biosciences, University of Graz, Graz, Austria.; BioHealth Field of Excellence, University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Sánchez-Murcia PA; Laboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Graz, Austria., Zangger K; Institute of Chemistry / Organic and Bioorganic Chemistry, Medical University of Graz, Graz, Austria.; BioHealth Field of Excellence, University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Pavkov-Keller T; Institute of Molecular Biosciences, University of Graz, Graz, Austria.; BioHealth Field of Excellence, University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Sep 28; Vol. 12. Date of Electronic Publication: 2023 Sep 28.
DOI:	10.7554/eLife.88721
Abstrakt:	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. Competing Interests: NG, TS, CB, BG, GW, LP, MG, MR, TB, IU, JR, PS, KZ, TP No competing interests declared, JS is affiliated with Redshift BioAnalytics, Inc which distributes the AQS3pro. Access to the AQS3pro instrument was provided to Nina Gubensäk as part of the RedShiftBio demo lab (© 2023, Gubensäk et al.)
Databáze:	MEDLINE
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