Quorum Sensing Modulators

Introduction

Quorum sensing is a chemical communication mechanism used by many common bacteria to initiate group behaviors. It plays an important role in the establishment of infection by pathogens and in mediating certain symbioses.1 As quorum sensing is dependent on small-molecule signals produced by the bacteria, there is significant interest in developing chemical strategies to interfere with these signals and attenuate quorum sensing-controlled behaviors. The Blackwell laboratory has developed several chemical tools that strongly modulate quorum sensing pathways in common Gram-negative bacteria by targeting LuxR-type receptors. A suite of the most versatile ligands (804223, 804231, 804258, 804339, 804347) are now available from Sigma-Aldrich for research purposes; their compound names from Blackwell group publications are provided next to the products below for reference.

Advantages

  • Amongst the most potent synthetic quorum sensing inhibitors and activators to be reported
  • Active in wild-type bacteria where many strongly modulate important quorum sensing phenotypes (motility, virulence factor production, etc.)
  • No effect on bacterial growth at standard concentrations
  • Bench stable; highly soluble in common biological media
  • 3-oxo-C12 aniline has enhanced hydrolytic stability relative to lactone tools

Representative Applications

Below is a depiction of quorum sensing where bacteria use receptors (green) to sense the signals (red) produced by nearby bacteria, allowing them to communicate the density of their population. As the concentration of signal increases with a growing population (quorum), bacteria adjust their behavior.1 Ligands from the Blackwell lab are valuable tools to modulate these receptors and thus quorum sensing-related processes. These compounds strongly inhibit or activate LasR, RhlR, and QscR from Pseudomonas aeruginosa,2–6 LuxR from Vibrio fischeri,7 TraR from Agrobacterium tumefaciens,2 the putative LuxR receptor (AbaR) from Acinetobacter baumannii,6 ExpR1/ExpR2 from Pectobacterium carotovora,9–10 and several other LuxR-type receptors from related species.12–13

Blackwell TS

Special thanks to Professor Helen Blackwell for contributing this technology spotlight.

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