Vibrio cholerae’s ToxRS bile sensing system
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/88721 |
| _version_ | 1797638411512709120 |
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| author | Nina Gubensäk Theo Sagmeister Christoph Buhlheller Bruno Di Geronimo Gabriel E Wagner Lukas Petrowitsch Melissa A Gräwert Markus Rotzinger Tamara M Ismael Berger Jan Schäfer Isabel Usón Joachim Reidl Pedro A Sánchez-Murcia Klaus Zangger Tea Pavkov-Keller |
| author_facet | Nina Gubensäk Theo Sagmeister Christoph Buhlheller Bruno Di Geronimo Gabriel E Wagner Lukas Petrowitsch Melissa A Gräwert Markus Rotzinger Tamara M Ismael Berger Jan Schäfer Isabel Usón Joachim Reidl Pedro A Sánchez-Murcia Klaus Zangger Tea Pavkov-Keller |
| author_sort | Nina Gubensäk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T13:03:12Z |
| format | Article |
| id | doaj.art-14240b0ac4a54de397f1b6609f309fb1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T13:03:12Z |
| publishDate | 2023-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-14240b0ac4a54de397f1b6609f309fb12023-11-03T15:37:37ZengeLife Sciences Publications LtdeLife2050-084X2023-09-011210.7554/eLife.88721Vibrio cholerae’s ToxRS bile sensing systemNina Gubensäk0https://orcid.org/0000-0002-0415-4299Theo Sagmeister1Christoph Buhlheller2Bruno Di Geronimo3Gabriel E Wagner4https://orcid.org/0000-0002-5704-3955Lukas Petrowitsch5Melissa A Gräwert6Markus Rotzinger7https://orcid.org/0000-0002-0411-3403Tamara M Ismael Berger8Jan Schäfer9Isabel Usón10Joachim Reidl11Pedro A Sánchez-Murcia12Klaus Zangger13Tea Pavkov-Keller14https://orcid.org/0000-0001-7871-6680Institute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaLaboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Graz, AustriaInstitute 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, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaBiological Small Angle Scattering, EMBL Hamburg, Hamburg, GermanyInstitute of Chemistry / Organic and Bioorganic Chemistry, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaRedShiftBio, Boxborough, United StatesInstitute of Molecular Biology of Barcelona, Barcelona, Spain; ICREA, Institució Catalana de Recerca i Estudis Avançats, Barcelona, SpainInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioHealth Field of Excellence, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, AustriaLaboratory of Computer-Aided Molecular Design, Division of Medicinal Chemistry, Otto-Loewi Research Center, Medical University of Graz, Graz, AustriaInstitute of Chemistry / Organic and Bioorganic Chemistry, Medical University of Graz, Graz, Austria; BioHealth Field of Excellence, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioHealth Field of Excellence, University of Graz, Graz, Austria; BioTechMed-Graz, Graz, AustriaThe 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.https://elifesciences.org/articles/88721Vibrio choleraeprotein interactionvirulence regulationtranscription factorsensory proteinsToxRS |
| spellingShingle | Nina Gubensäk Theo Sagmeister Christoph Buhlheller Bruno Di Geronimo Gabriel E Wagner Lukas Petrowitsch Melissa A Gräwert Markus Rotzinger Tamara M Ismael Berger Jan Schäfer Isabel Usón Joachim Reidl Pedro A Sánchez-Murcia Klaus Zangger Tea Pavkov-Keller Vibrio cholerae’s ToxRS bile sensing system eLife Vibrio cholerae protein interaction virulence regulation transcription factor sensory proteins ToxRS |
| title | Vibrio cholerae’s ToxRS bile sensing system |
| title_full | Vibrio cholerae’s ToxRS bile sensing system |
| title_fullStr | Vibrio cholerae’s ToxRS bile sensing system |
| title_full_unstemmed | Vibrio cholerae’s ToxRS bile sensing system |
| title_short | Vibrio cholerae’s ToxRS bile sensing system |
| title_sort | vibrio cholerae s toxrs bile sensing system |
| topic | Vibrio cholerae protein interaction virulence regulation transcription factor sensory proteins ToxRS |
| url | https://elifesciences.org/articles/88721 |
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