| Título: | Regulation of Vibrio cholerae Quorum Sensing |
| Autores: | Wei, Yunzhou |
| Fecha: |
2012-08-01 2012-08-01 2012 |
| Publicador: | Princeton, NJ : Princeton University |
| Fuente: |
Ver documento |
| Tipo: | Academic dissertations (Ph.D.) |
| Tema: |
autoinducer CAI-1 CqsS histidine kinase quorum sensing virulence Molecular biology |
| Descripción: | Quorum sensing is a cell-cell communication process that bacteria use to assess their population densities and to regulate gene expression accordingly. Quorum sensing relies on the production, secretion, and detection of small signaling molecules called autoinducers. This process enables groups of bacteria to behave as collectives. Vibrio cholerae, a human pathogen that causes the disease cholera, uses quorum sensing to regulate virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system is the CqsA/CqsS system. CqsA is the autoinducer synthase which produces the autoinducer CAI-1, (S)-3-hydroxytridecan-4-one. CqsS, a membrane-bound histidine kinase, is the CAI-1 receptor. This thesis investigates the interactions between CAI-1 and CqsS. Using a chemical-genetics approach with CAI-1 and synthetic analogs compared with CqsS mutants, gate-keeper residues that dictate ligand specificities were identified. In addition, the biosynthetic route to CAI-1 was defined. CqsA ligates (S)-adenosylmethionine to decanoyl-coenzyme A while eliminating (S)-methyl-5'-thioadenosine and coenzyme A, resulting in the formation of 3-aminotridec-2-en-4-one (Ea-CAI-1). Ea-CAI-1 is converted to CAI-1 through two additional steps. The chemical structure of CAI-1 of Vibrio harveyi, a relative of V. cholerae, was identified. The V. harveyi CAI-1 is the immediate product of the V. harveyi CqsA catalyzed reaction, (Z)-3-aminoundec-2-en-4-one (Ea-C8-CAI-1). Ea-C8-CAI-1 is likely the signal that different vibrios use to communicate with each other. Lastly, the mechanism of CAI-1 regulation of CqsS was investigated in vitro using a reconstituted phosphorylation cascade. CAI-1 inhibits auto-phosphorylation of CqsS, but CAI-1 does not affect downstream phosphotransfer processes or CqsS phosphatase activity. CAI-1 binding causes a conformational change in CqsS that renders the histidine in the dimerization histidine phosphotransfer domain inaccessible to the catalytic ATP binding domain. |
| Idioma: | Inglés |
1 Engineering solutions for a carbon-constrained world por Celia, M. A.,Nordbotten, J. M. | 6 Impact of capillary forces on large-scale migration of CO2 por Nordbotten, Jan M.,Dahle, Helge K. |
2 Analysis of Plume Extent using Analytical Solutions for CO2 Storage por Nordbotten, Jan M.,Celia, Michael A. | 7 Impact of geological heterogeneity on early-stage CO2 plume migration por Ashraf, Meisam,Lie, Knut-Andreas,Nilsen, Halvor M.,Nordbotten, Jan M.,Skorstad, Arne |
3 A model-oriented benchmark problem for CO2 storage por Dahle, Helge K.,Eigestad, Geir T.,Nordbotten, Jan M.,Pruess, K. | 8 CO2 trapping in sloping aqiufers: High resolution numerical simulations por Elenius, Maria,Tchelepi, Hamdi,Johannsen, Klaus |
4 Report from CO2 storage workshop por Dahle, Helge K.,Lien, Martha,Nordbotten, Jan M.,Lie, Knut-Andreas,Braathen, Alvar,Helmig, Rainer,Class, Holger,Celia, Michael A. | 9 Streamline methods for parabolic differential equations por Hafver, Jørn |
5 Summary of Princeton Workshop on Geological Storage of CO2 por Celia, Michael A.,Nordbotten, Jan M.,Bachu, Stefan,Kavetski, Dmitri,Gasda, Sarah | 10 Vertically Averaged Models for CO2 Storage in Porous Media por Hammer, Andreas |