Abstract
The transcription factor QscR is a regulator of quorum sensing in Pseudomonas aeruginosa and plays a role in controlling virulence in this prevalent opportunistic pathogen. This study outlines the discovery of a set of synthetic N-acylated homoserine lactones that are capable of either activating or strongly inhibiting QscR in a cell-based reporter gene assay. We demonstrate that the synthetic antagonists inhibit ligand-dependent QscR binding to DNA. Several of these ligands can selectively modulate QscR instead of LasR, or modulate the activity of both receptors, and represent new chemical tools to study the hierarchy of quorum-sensing signaling in P. aeruginosa.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acyl-Butyrolactones / chemical synthesis*
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Acyl-Butyrolactones / chemistry
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Acyl-Butyrolactones / pharmacology*
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / agonists*
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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DNA, Bacterial / metabolism
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Dose-Response Relationship, Drug
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Drug Design*
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Ligands
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Pseudomonas aeruginosa / drug effects*
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Pseudomonas aeruginosa / metabolism
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Repressor Proteins / agonists*
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Repressor Proteins / antagonists & inhibitors*
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Repressor Proteins / metabolism
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Signal Transduction / drug effects
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Virulence Factors / agonists
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Virulence Factors / antagonists & inhibitors
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Virulence Factors / metabolism
Substances
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Acyl-Butyrolactones
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Anti-Bacterial Agents
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Bacterial Proteins
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DNA, Bacterial
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Ligands
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QscR protein, Pseudomonas aeruginosa
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Repressor Proteins
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Virulence Factors