Phenotypic Discovery of an Antivirulence Agent against <i>Vibrio vulnificus</i> via Modulation of Quorum-Sensing Regulator SmcR
Seung Min Kim, Jongmin Park, Myun Soo Kim, Heebum Song, Ala Jo, Hankum Park, Tae Sung Kim, Sang Ho Choi, Seung Bum Park
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.