A Strategy for Antagonizing Quorum Sensing
Quorum-sensing bacteria communicate via small molecules called autoinducers to coordinate collective behaviors. Because quorum sensing controls virulence factor expression in many clinically relevant pathogens, membrane-permeable quorum sensing antagonists that prevent population-wide expression of virulence genes offer a potential route to novel antibacterial therapeutics. Here, we report a strategy for inhibiting quorum-sensing receptors of the widespread LuxR family. Structure-function studies with natural and synthetic ligands demonstrate that the dimeric LuxR-type transcription factor CviR from Chromobacterium violaceum is potently antagonized by molecules that bind in place of the native acylated homoserine lactone autoinducer, provided that they stabilize a closed conformation. In such conformations, each of the two DNA-binding domains interacts with the ligand-binding domain of the opposing monomer. Consequently, the DNA-binding helices are held apart by {approx}60 {angstrom}, twice the {approx}30 {angstrom} separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE SC OFFICE OF SCIENCE (SC)
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1042039
- Report Number(s):
- BNL-97717-2012-JA; TRN: US201212%%450
- Journal Information:
- Molecular Cell, Vol. 42, Issue 2; ISSN 1097-2765
- Country of Publication:
- United States
- Language:
- English
Similar Records
Switch of SpnR function from activating to inhibiting quorum sensing by its exogenous addition
Structural and Mechanistic Roles of Novel Chemical Ligands on the SdiA Quorum-Sensing Transcription Regulator