TY - JOUR
T1 - Deducing Receptor Signaling Parameters from In Vivo Analysis
T2 - LuxN/AI-1 Quorum Sensing in Vibrio harveyi
AU - Swem, Lee R.
AU - Swem, Danielle L.
AU - Wingreen, Ned S.
AU - Bassler, Bonnie L.
N1 - Funding Information:
This work was supported by the Howard Hughes Medical Institute, National Institutes of Health (NIH) grant 5R01GM065859, NIH grant 5R01 AI 054442, National Science Foundation grant MCB-0343821 to B.L.B., and NIH postdoctoral fellowship GM787552 to L.R.S. The antagonist screen has been funded in whole or in part with Federal funds from the National Cancer Institute's Initiative for Chemical Genetics, NIH, under contract number N01-CO-12400 and has been performed with the assistance of the Chemical Biology Platform of the Broad Institute of Harvard and MIT. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Service, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
PY - 2008/8/8
Y1 - 2008/8/8
N2 - Quorum sensing, a process of bacterial cell-cell communication, relies on production, detection, and response to autoinducer signaling molecules. LuxN, a nine-transmembrane domain protein from Vibrio harveyi, is the founding example of membrane-bound receptors for acyl-homoserine lactone (AHL) autoinducers. We used mutagenesis and suppressor analyses to identify the AHL-binding domain of LuxN and discovered LuxN mutants that confer both decreased and increased AHL sensitivity. Our analysis of dose-response curves of multiple LuxN mutants pins these inverse phenotypes on quantifiable opposing shifts in the free-energy bias of LuxN for occupying its kinase and phosphatase states. To understand receptor activation and to characterize the pathway signaling parameters, we exploited a strong LuxN antagonist, one of fifteen small-molecule antagonists we identified. We find that quorum-sensing-mediated communication can be manipulated positively and negatively to control bacterial behavior and, more broadly, that signaling parameters can be deduced from in vivo data.
AB - Quorum sensing, a process of bacterial cell-cell communication, relies on production, detection, and response to autoinducer signaling molecules. LuxN, a nine-transmembrane domain protein from Vibrio harveyi, is the founding example of membrane-bound receptors for acyl-homoserine lactone (AHL) autoinducers. We used mutagenesis and suppressor analyses to identify the AHL-binding domain of LuxN and discovered LuxN mutants that confer both decreased and increased AHL sensitivity. Our analysis of dose-response curves of multiple LuxN mutants pins these inverse phenotypes on quantifiable opposing shifts in the free-energy bias of LuxN for occupying its kinase and phosphatase states. To understand receptor activation and to characterize the pathway signaling parameters, we exploited a strong LuxN antagonist, one of fifteen small-molecule antagonists we identified. We find that quorum-sensing-mediated communication can be manipulated positively and negatively to control bacterial behavior and, more broadly, that signaling parameters can be deduced from in vivo data.
KW - MICROBIO
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U2 - 10.1016/j.cell.2008.06.023
DO - 10.1016/j.cell.2008.06.023
M3 - Article
C2 - 18692469
AN - SCOPUS:48449103829
VL - 134
SP - 461
EP - 473
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -