Relacin, a novel antibacterial agent targeting the Stringent Response.

Finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. We present a novel compound, Relacin, designed to inhibit (p)ppGpp production by the ubiquitous bacterial enzyme RelA that triggers the Stringent Response. Rela...

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Autores principales:	Ezequiel Wexselblatt, Yaara Oppenheimer-Shaanan, Ilana Kaspy, Nir London, Ora Schueler-Furman, Eylon Yavin, Gad Glaser, Joshua Katzhendler, Sigal Ben-Yehuda
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/d1f6e73e68eb43c99e4dd57e26c58e24
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spelling	oai:doaj.org-article:d1f6e73e68eb43c99e4dd57e26c58e242021-11-18T06:03:56ZRelacin, a novel antibacterial agent targeting the Stringent Response.1553-73661553-737410.1371/journal.ppat.1002925https://doaj.org/article/d1f6e73e68eb43c99e4dd57e26c58e242012-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028324/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. We present a novel compound, Relacin, designed to inhibit (p)ppGpp production by the ubiquitous bacterial enzyme RelA that triggers the Stringent Response. Relacin inhibits RelA in vitro and reduces (p)ppGpp production in vivo. Moreover, Relacin affects entry into stationary phase in Gram positive bacteria, leading to a dramatic reduction in cell viability. When Relacin is added to sporulating Bacillus subtilis cells, it strongly perturbs spore formation regardless of the time of addition. Spore formation is also impeded in the pathogenic bacterium Bacillus anthracis that causes the acute anthrax disease. Finally, the formation of multicellular biofilms is markedly disrupted by Relacin. Thus, we establish that Relacin, a novel ppGpp analogue, interferes with bacterial long term survival strategies, placing it as an attractive new antibacterial agent.Ezequiel WexselblattYaara Oppenheimer-ShaananIlana KaspyNir LondonOra Schueler-FurmanEylon YavinGad GlaserJoshua KatzhendlerSigal Ben-YehudaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 9, p e1002925 (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 Ezequiel Wexselblatt Yaara Oppenheimer-Shaanan Ilana Kaspy Nir London Ora Schueler-Furman Eylon Yavin Gad Glaser Joshua Katzhendler Sigal Ben-Yehuda Relacin, a novel antibacterial agent targeting the Stringent Response.
description	Finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. We present a novel compound, Relacin, designed to inhibit (p)ppGpp production by the ubiquitous bacterial enzyme RelA that triggers the Stringent Response. Relacin inhibits RelA in vitro and reduces (p)ppGpp production in vivo. Moreover, Relacin affects entry into stationary phase in Gram positive bacteria, leading to a dramatic reduction in cell viability. When Relacin is added to sporulating Bacillus subtilis cells, it strongly perturbs spore formation regardless of the time of addition. Spore formation is also impeded in the pathogenic bacterium Bacillus anthracis that causes the acute anthrax disease. Finally, the formation of multicellular biofilms is markedly disrupted by Relacin. Thus, we establish that Relacin, a novel ppGpp analogue, interferes with bacterial long term survival strategies, placing it as an attractive new antibacterial agent.
format	article
author	Ezequiel Wexselblatt Yaara Oppenheimer-Shaanan Ilana Kaspy Nir London Ora Schueler-Furman Eylon Yavin Gad Glaser Joshua Katzhendler Sigal Ben-Yehuda
author_facet	Ezequiel Wexselblatt Yaara Oppenheimer-Shaanan Ilana Kaspy Nir London Ora Schueler-Furman Eylon Yavin Gad Glaser Joshua Katzhendler Sigal Ben-Yehuda
author_sort	Ezequiel Wexselblatt
title	Relacin, a novel antibacterial agent targeting the Stringent Response.
title_short	Relacin, a novel antibacterial agent targeting the Stringent Response.
title_full	Relacin, a novel antibacterial agent targeting the Stringent Response.
title_fullStr	Relacin, a novel antibacterial agent targeting the Stringent Response.
title_full_unstemmed	Relacin, a novel antibacterial agent targeting the Stringent Response.
title_sort	relacin, a novel antibacterial agent targeting the stringent response.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d1f6e73e68eb43c99e4dd57e26c58e24
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Relacin, a novel antibacterial agent targeting the Stringent Response.

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