Phenotypic Discovery of an Antivirulence Agent against Vibrio vulnificus 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

doi:10.1021/acsinfecdis.0c00587

Phenotypic Discovery of an Antivirulence Agent against Vibrio vulnificus 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

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Pages (from-to)	3076-3082
Number of pages	7
Journal	ACS Infectious Diseases
Volume	6
Issue number	11
DOIs	https://doi.org/10.1021/acsinfecdis.0c00587
State	Published - 13 Nov 2020

Bibliographical note

Publisher Copyright:
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Keywords

antivirulence agent
quorum sensing
SmcR
target identification
Vibrio vulnificus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsinfecdis.0c00587

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

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 = "antivirulence agent, quorum sensing, SmcR, target identification, Vibrio vulnificus",

author = "Kim, \{Seung Min\} and Jongmin Park and Kim, \{Myun Soo\} and Heebum Song and Ala Jo and Hankum Park and Kim, \{Tae Sung\} and Choi, \{Sang Ho\} and Park, \{Seung Bum\}",

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year = "2020",

month = nov,

day = "13",

doi = "10.1021/acsinfecdis.0c00587",

language = "English",

volume = "6",

pages = "3076--3082",

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T1 - Phenotypic Discovery of an Antivirulence Agent against Vibrio vulnificus via Modulation of Quorum-Sensing Regulator SmcR

AU - Kim, Seung Min

AU - Park, Jongmin

AU - Kim, Myun Soo

AU - Song, Heebum

AU - Jo, Ala

AU - Park, Hankum

AU - Kim, Tae Sung

AU - Choi, Sang Ho

AU - Park, Seung Bum

N1 - Publisher Copyright: ©

PY - 2020/11/13

Y1 - 2020/11/13

N2 - 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.

AB - 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.

KW - antivirulence agent

KW - quorum sensing

KW - SmcR

KW - target identification

KW - Vibrio vulnificus

UR - https://www.scopus.com/pages/publications/85096071550

U2 - 10.1021/acsinfecdis.0c00587

DO - 10.1021/acsinfecdis.0c00587

M3 - Article

C2 - 33086782

AN - SCOPUS:85096071550

SN - 2373-8227

VL - 6

SP - 3076

EP - 3082

JO - ACS Infectious Diseases

JF - ACS Infectious Diseases

IS - 11

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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