Phenotypic Discovery of an Antivirulence Agent against Vibrio vulnificus via Modulation of Quorum-Sensing Regulator SmcR

  • ACS Infect Dis. 2020 Nov 13;6(11):3076-3082. doi: 10.1021/acsinfecdis.0c00587.
Seung Min Kim  1 ,  Jongmin Park  2 ,  Myun Soo Kim  3 ,  Heebum Song  2 ,  Ala Jo  2 ,  Hankum Park  2 ,  Tae Sung Kim  3 ,  Sang Ho Choi  1 ,  Seung Bum Park  2
Affiliations
  • 1. Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea.
  • 2. CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul 08826, Korea.
  • 3. Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
PMID: 33086782 DOI: 10.1021/acsinfecdis.0c00587
Abstract

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.

Keywords
SmcR; Vibrio vulnificus; antivirulence agent; quorum sensing; target identification.
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