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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02262-17 |
| _version_ | 1831632174310227968 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T05:13:17Z |
| format | Article |
| id | doaj.art-577231cced5d4551b4b97f5b9821e22a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T05:13:17Z |
| publishDate | 2018-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-577231cced5d4551b4b97f5b9821e22a2022-12-21T20:34:44ZengAmerican Society for MicrobiologymBio2150-75112018-03-019110.1128/mBio.02262-17QStatin, a Selective Inhibitor of Quorum Sensing in <italic toggle="yes">Vibrio</italic> SpeciesByoung Sik Kim0Song Yee Jang1Ye-ji Bang2Jungwon Hwang3Youngwon Koo4Kyung Ku Jang5Dongyeol Lim6Myung Hee Kim7Sang Ho Choi8National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University, Seoul, South KoreaInfection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaNational Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University, Seoul, South KoreaInfection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaDepartment of Chemistry, Sejong University, Seoul, South KoreaNational Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University, Seoul, South KoreaDepartment of Chemistry, Sejong University, Seoul, South KoreaInfection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaNational Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University, Seoul, South KoreaABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02262-17LuxRVibrioquorum sensingquorum-sensing inhibitor |
| spellingShingle | 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 mBio LuxR Vibrio quorum sensing quorum-sensing inhibitor |
| title | 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_short | 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 |
| topic | LuxR Vibrio quorum sensing quorum-sensing inhibitor |
| url | https://journals.asm.org/doi/10.1128/mBio.02262-17 |
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