Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress viru...

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Autores principales:	Wai-Leung Ng, Lark Perez, Jianping Cong, Martin F Semmelhack, Bonnie L Bassler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/121e3c97499a4a24a44d02e64c0df70b
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spelling	oai:doaj.org-article:121e3c97499a4a24a44d02e64c0df70b2021-11-18T06:04:16ZBroad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.1553-73661553-737410.1371/journal.ppat.1002767https://doaj.org/article/121e3c97499a4a24a44d02e64c0df70b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761573/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.Wai-Leung NgLark PerezJianping CongMartin F SemmelhackBonnie L BasslerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002767 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
description	Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.
format	article
author	Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler
author_facet	Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler
author_sort	Wai-Leung Ng
title	Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
title_short	Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
title_full	Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
title_fullStr	Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
title_full_unstemmed	Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
title_sort	broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/121e3c97499a4a24a44d02e64c0df70b
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Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.

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