Phenotypic Discovery of an Antivirulence Agent against Vibrio vulnificus via Modulation of Quorum-Sensing Regulator SmcR.
Seung Min KimJongmin ParkMyun Soo KimHeebum SongAla JoHankum ParkTae Sung KimSang Ho ChoiJong Beom ParkPublished in: ACS infectious diseases (2020)
An antivirulence agent against Vibrio vulnificus named quoromycin (QM) was discovered by a phenotype-based elastase inhibitor screening. Using the fluorescence difference in two-dimensional gel electrophoresis (FITGE) approach, SmcR, a quorum-sensing master regulator and homologue of LuxR, was identified as the target protein of QM. We confirmed that the direct binding of QM to SmcR inhibits the quorum-sensing signaling pathway by controlling the DNA-binding affinity of SmcR and thus effectively alleviates the virulence of V. vulnificus in vitro and in vivo. QM can be regarded as a novel antivirulence agent for the treatment of V. vulnificus infection.
Keyphrases
- dna binding
- transcription factor
- biofilm formation
- signaling pathway
- escherichia coli
- pseudomonas aeruginosa
- binding protein
- epithelial mesenchymal transition
- high throughput
- antimicrobial resistance
- single molecule
- mouse model
- protein protein
- candida albicans
- induced apoptosis
- hyaluronic acid
- wound healing
- quantum dots