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The Pseudomonas aeruginosa LasR quorum-sensing receptor balances ligand selectivity and sensitivity

Amelia R. McCready, Jon E. Paczkowski, Brad R. Henke, Bonnie L. Bassler
doi: https://doi.org/10.1101/269001
Amelia R. McCready
1The Department of Molecular Biology, Princeton University, Princeton, NJ 08544
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Jon E. Paczkowski
1The Department of Molecular Biology, Princeton University, Princeton, NJ 08544
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Brad R. Henke
2Opti-Mol Consulting, LLC, Cary, NC 27513
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Bonnie L. Bassler
1The Department of Molecular Biology, Princeton University, Princeton, NJ 08544
3Howard Hughes Medical Institute, Chevy Chase, MD 20815
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  • For correspondence: bbassler@princeton.edu
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Abstract

Quorum sensing is a cell-cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by extracellular signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use the Pseudomonas aeruginosa LasR quorum-sensing receptor to explore receptor sensitivity and selectivity. Alteration of LasR amino acid S129 increases ligand selectivity and decreases ligand sensitivity. Conversely, the L130F mutation enhances LasR sensitivity while reducing selectivity. We solve crystal structures of LasR ligand binding domains complexed with non-cognate autoinducers. Comparison to existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop adjacent to the ligand binding site. We show that P. aeruginosa harboring LasR variants with modified selectivity or sensitivity exhibit altered quorum-sensing responses. We suggest that an evolutionary trade-off between ligand selectivity and sensitivity enables LasR to optimally regulate quorum-sensing traits.

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Posted March 18, 2018.
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The Pseudomonas aeruginosa LasR quorum-sensing receptor balances ligand selectivity and sensitivity
Amelia R. McCready, Jon E. Paczkowski, Brad R. Henke, Bonnie L. Bassler
bioRxiv 269001; doi: https://doi.org/10.1101/269001
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The Pseudomonas aeruginosa LasR quorum-sensing receptor balances ligand selectivity and sensitivity
Amelia R. McCready, Jon E. Paczkowski, Brad R. Henke, Bonnie L. Bassler
bioRxiv 269001; doi: https://doi.org/10.1101/269001

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