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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 Park
Published 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.
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