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.
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
UR - http://www.scopus.com/inward/record.url?scp=48449103829&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48449103829&partnerID=8YFLogxK
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 -