QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species

ABSTRACT Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic...

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Autores principales:	Byoung Sik Kim, Song Yee Jang, Ye-ji Bang, Jungwon Hwang, Youngwon Koo, Kyung Ku Jang, Dongyeol Lim, Myung Hee Kim, Sang Ho Choi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	LuxR Vibrio quorum sensing quorum-sensing inhibitor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/577231cced5d4551b4b97f5b9821e22a
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spelling	oai:doaj.org-article:577231cced5d4551b4b97f5b9821e22a2021-11-15T15:53:26ZQStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species10.1128/mBio.02262-172150-7511https://doaj.org/article/577231cced5d4551b4b97f5b9821e22a2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02262-17https://doaj.org/toc/2150-7511ABSTRACT Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of Vibrio species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective Vibrio QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affects Vibrio harveyi LuxR homologues, the well-conserved master transcriptional regulators for QS in Vibrio species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in V. vulnificus, and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various Vibrio species, including virulence against the brine shrimp (Artemia franciscana). Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of Vibrio species in aquacultures. IMPORTANCE Yields of aquaculture, such as penaeid shrimp hatcheries, are greatly affected by vibriosis, a disease caused by pathogenic Vibrio infections. Since bacterial cell-to-cell communication, known as quorum sensing (QS), regulates pathogenesis of Vibrio species in marine environments, QS inhibitors have attracted attention as alternatives to conventional antibiotics in aquatic settings. Here, we used target-based high-throughput screening to identify QStatin, a potent and selective inhibitor of V. harveyi LuxR homologues, which are well-conserved master QS regulators in Vibrio species. Structural and biochemical analyses revealed that QStatin binds tightly to a putative ligand-binding pocket on SmcR, the LuxR homologue in V. vulnificus, and affects expression of QS-regulated genes. Remarkably, QStatin attenuated diverse QS-regulated phenotypes in various Vibrio species, including pathogenesis against brine shrimp, with no impact on bacterial viability. Taken together, the results suggest that QStatin may be a sustainable antivibriosis agent useful in aquacultures.Byoung Sik KimSong Yee JangYe-ji BangJungwon HwangYoungwon KooKyung Ku JangDongyeol LimMyung Hee KimSang Ho ChoiAmerican Society for MicrobiologyarticleLuxRVibrioquorum sensingquorum-sensing inhibitorMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	LuxR Vibrio quorum sensing quorum-sensing inhibitor Microbiology QR1-502
spellingShingle	LuxR Vibrio quorum sensing quorum-sensing inhibitor Microbiology QR1-502 Byoung Sik Kim Song Yee Jang Ye-ji Bang Jungwon Hwang Youngwon Koo Kyung Ku Jang Dongyeol Lim Myung Hee Kim Sang Ho Choi QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
description	ABSTRACT Pathogenic Vibrio species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of Vibrio species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective Vibrio QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affects Vibrio harveyi LuxR homologues, the well-conserved master transcriptional regulators for QS in Vibrio species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in V. vulnificus, and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various Vibrio species, including virulence against the brine shrimp (Artemia franciscana). Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of Vibrio species in aquacultures. IMPORTANCE Yields of aquaculture, such as penaeid shrimp hatcheries, are greatly affected by vibriosis, a disease caused by pathogenic Vibrio infections. Since bacterial cell-to-cell communication, known as quorum sensing (QS), regulates pathogenesis of Vibrio species in marine environments, QS inhibitors have attracted attention as alternatives to conventional antibiotics in aquatic settings. Here, we used target-based high-throughput screening to identify QStatin, a potent and selective inhibitor of V. harveyi LuxR homologues, which are well-conserved master QS regulators in Vibrio species. Structural and biochemical analyses revealed that QStatin binds tightly to a putative ligand-binding pocket on SmcR, the LuxR homologue in V. vulnificus, and affects expression of QS-regulated genes. Remarkably, QStatin attenuated diverse QS-regulated phenotypes in various Vibrio species, including pathogenesis against brine shrimp, with no impact on bacterial viability. Taken together, the results suggest that QStatin may be a sustainable antivibriosis agent useful in aquacultures.
format	article
author	Byoung Sik Kim Song Yee Jang Ye-ji Bang Jungwon Hwang Youngwon Koo Kyung Ku Jang Dongyeol Lim Myung Hee Kim Sang Ho Choi
author_facet	Byoung Sik Kim Song Yee Jang Ye-ji Bang Jungwon Hwang Youngwon Koo Kyung Ku Jang Dongyeol Lim Myung Hee Kim Sang Ho Choi
author_sort	Byoung Sik Kim
title	QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
title_short	QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
title_full	QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
title_fullStr	QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
title_full_unstemmed	QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species
title_sort	qstatin, a selective inhibitor of quorum sensing in <italic toggle="yes">vibrio</italic> species
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/577231cced5d4551b4b97f5b9821e22a
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QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> Species

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