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Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
Biomedical Engineering, Department of Electrical Engineering, Ørsteds Plads 349, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark
Costerton Biofilm Center, Department of International Health, Immunology, and Microbiology, Panum Institute, University of Copenhagen, Blegdamsvej 3B, Copenhagen DK-2200, Denmark
Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore
Department of Biochemistry, University of Cambridge, Hopkins Building, Downing Site, Cambridge CB2 1QW, UK
Center for Biological Sequence Analysis, Department of Systems Biology, Building 301, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark
* Author to whom correspondence should be addressed.
Received: 3 June 2013; in revised form: 19 June 2013 / Accepted: 20 June 2013 / Published: 27 June 2013
Abstract: We propose a kinetic model for the activation of the las regulon in the opportunistic pathogen Pseudomonas aeruginosa. The model is based on in vitro data and accounts for the LasR dimerization and consecutive activation by binding of two OdDHL signal molecules. Experimentally, the production of the active LasR quorum-sensing regulator was studied in an Escherichia coli background as a function of signal molecule concentration. The functional activity of the regulator was monitored via a GFP reporter fusion to lasB expressed from the native lasB promoter. The new data shows that the active form of the LasR dimer binds two signal molecules cooperatively and that the timescale for reaching saturation is independent of the signal molecule concentration. This favors a picture where the dimerized regulator is protected against proteases and remains protected as it is activated through binding of two successive signal molecules. In absence of signal molecules, the dimerized regulator can dissociate and degrade through proteolytic turnover of the monomer. This resolves the apparent contradiction between our data and recent reports that the fully protected dimer is able to “degrade” when the induction of LasR ceases.
Keywords: quorum sensing; LasR; Pseudomonas aeruginosa; OdDHL; C12-HSL; signal molecule; ligand
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Claussen, A.; Jakobsen, T.H.; Bjarnsholt, T.; Givskov, M.; Welch, M.; Ferkinghoff-Borg, J.; Sams, T. Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR. Int. J. Mol. Sci. 2013, 14, 13360-13376.
Claussen A, Jakobsen TH, Bjarnsholt T, Givskov M, Welch M, Ferkinghoff-Borg J, Sams T. Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR. International Journal of Molecular Sciences. 2013; 14(7):13360-13376.
Claussen, Anetta; Jakobsen, Tim H.; Bjarnsholt, Thomas; Givskov, Michael; Welch, Martin; Ferkinghoff-Borg, Jesper; Sams, Thomas. 2013. "Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR." Int. J. Mol. Sci. 14, no. 7: 13360-13376.