Bile salt receptor complex activates a pathogenic type III secretion system
Abstract
Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.
- Authors:
-
[3];
[5]
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
- Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
- Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1260282
- Alternate Identifier(s):
- OSTI ID: 1260283
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Published Article
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Name: eLife Journal Volume: 5; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Li, Peng, Rivera-Cancel, Giomar, Kinch, Lisa N., Salomon, Dor, Tomchick, Diana R., Grishin, Nick V., and Orth, Kim. Bile salt receptor complex activates a pathogenic type III secretion system. United States: N. p., 2016.
Web. doi:10.7554/eLife.15718.
Li, Peng, Rivera-Cancel, Giomar, Kinch, Lisa N., Salomon, Dor, Tomchick, Diana R., Grishin, Nick V., & Orth, Kim. Bile salt receptor complex activates a pathogenic type III secretion system. United States. https://doi.org/10.7554/eLife.15718
Li, Peng, Rivera-Cancel, Giomar, Kinch, Lisa N., Salomon, Dor, Tomchick, Diana R., Grishin, Nick V., and Orth, Kim. Tue .
"Bile salt receptor complex activates a pathogenic type III secretion system". United States. https://doi.org/10.7554/eLife.15718.
@article{osti_1260282,
title = {Bile salt receptor complex activates a pathogenic type III secretion system},
author = {Li, Peng and Rivera-Cancel, Giomar and Kinch, Lisa N. and Salomon, Dor and Tomchick, Diana R. and Grishin, Nick V. and Orth, Kim},
abstractNote = {Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.},
doi = {10.7554/eLife.15718},
journal = {eLife},
number = ,
volume = 5,
place = {United States},
year = {Tue Jul 05 00:00:00 EDT 2016},
month = {Tue Jul 05 00:00:00 EDT 2016}
}
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