Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi.

TitleDeducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi.
Publication TypeJournal Article
Year of Publication2008
AuthorsSwem, LR, Swem, DL, Wingreen, NS, Bassler, BL
JournalCell
Volume134
Issue3
Pagination461-73
Date Published2008 Aug 8
ISSN1097-4172
Keywords4-Butyrolactone, Acyl-Butyrolactones, Amino Acid Sequence, Bacterial Proteins, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Kinases, Protein Structure, Tertiary, Quorum Sensing, Transcription Factors, Vibrio
Abstract

<p>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.</p>

DOI10.1016/j.cell.2008.06.023
Alternate JournalCell
PubMed ID18692469
PubMed Central IDPMC2585989
Grant List5R01 AI 054442 / AI / NIAID NIH HHS / United States
5R01GM065859 / GM / NIGMS NIH HHS / United States
GM787552 / GM / NIGMS NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
R01 GM065859-05A1 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
/ / Howard Hughes Medical Institute / United States