The quorum-sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2-thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure-activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3-phenyl-1-(thiophen-2-ylsulfonyl)-1H-pyrazole), inhibits quorum sensing in multiple strains of V. vulnificus, V. parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand-binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfon...Continue Reading
Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators
Characterization of hapR, a positive regulator of the Vibrio cholerae HA/protease gene hap, and its identification as a functional homologue of the Vibrio harveyi luxR gene
Regulation of metalloprotease gene expression in Vibrio vulnificus by a Vibrio harveyi LuxR homologue
A constitutively active variant of the quorum-sensing regulator LuxO affects protease production and biofilm formation in Vibrio cholerae.
SmcR and cyclic AMP receptor protein coactivate Vibrio vulnificus vvpE encoding elastase through the RpoS-dependent promoter in a synergistic manner.
Requirements for Vibrio cholerae HapR binding and transcriptional repression at the hapR promoter are distinct from those at the aphA promoter
The natural furanone (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone disrupts quorum sensing-regulated gene expression in Vibrio harveyi by decreasing the DNA-binding activity of the transcriptional regulator protein luxR
Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT.
A consensus sequence for binding of SmcR, a Vibrio vulnificus LuxR homologue, and genome-wide identification of the SmcR regulon.
Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR.
Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs.
Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription.
Structure-activity relationship of cinnamaldehyde analogs as inhibitors of AI-2 based quorum sensing and their effect on virulence of Vibrio spp.
Increasing rates of vibriosis in the United States, 1996-2010: review of surveillance data from 2 systems.
A quorum sensing-disrupting brominated thiophenone with a promising therapeutic potential to treat luminescent vibriosis.
Individual and combined roles of the master regulators AphA and LuxR in control of the Vibrio harveyi quorum-sensing regulon
LuxR homologue SmcR is essential for Vibrio vulnificus pathogenesis and biofilm detachment, and its expression is induced by host cells
A nitric oxide-responsive quorum sensing circuit in Vibrio harveyi regulates flagella production and biofilm formation
Identification of anti-virulence compounds that disrupt quorum-sensing regulated acute and persistent pathogenicity
Binding mode exploration of LuxR-thiazolidinedione analogues, e-pharmacophore-based virtual screening in the designing of LuxR inhibitors and its biological evaluation
Integration host factor and LuxR synergistically bind DNA to coactivate quorum-sensing genes in Vibrio harveyi
Climate influence on Vibrio and associated human diseases during the past half-century in the coastal North Atlantic
Discovery of potent inhibitors targeting Vibrio harveyi LuxR through shape and e-pharmacophore based virtual screening and its biological evaluation
Effect of Quorum Quenching Lactonase in Clinical Isolates of Pseudomonas aeruginosa and Comparison with Quorum Sensing Inhibitors
Promoter Boundaries for the luxCDABE and betIBA-proXWV Operons in Vibrio harveyi Defined by the Method Rapid Arbitrary PCR Insertion Libraries (RAIL)
The master quorum-sensing regulators LuxR/HapR directly interact with the alpha subunit of RNA polymerase to drive transcription activation in Vibrio harveyi and Vibrio cholerae
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