DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ

Suppression of the stringent response is a promising strategy for the treatment of persistent bacterial infections. A novel class of compounds having a mechanism of action based on alarmone synthetase inhibition and suppressing the synthesis of (p)ppGpp alarmones in bacteria may provide a more effec...

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Main Authors: Sidorov Roman Yu., Tkachenko Alexander G.
Format: Article
Language:English
Published: EDP Sciences 2023-01-01
Series:BIO Web of Conferences
Online Access:https://www.bio-conferences.org/articles/bioconf/pdf/2023/02/bioconf_itsm2023_08002.pdf
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author Sidorov Roman Yu.
Tkachenko Alexander G.
author_facet Sidorov Roman Yu.
Tkachenko Alexander G.
author_sort Sidorov Roman Yu.
collection DOAJ
description Suppression of the stringent response is a promising strategy for the treatment of persistent bacterial infections. A novel class of compounds having a mechanism of action based on alarmone synthetase inhibition and suppressing the synthesis of (p)ppGpp alarmones in bacteria may provide a more effective treatment for latent infections and resolve problems associated with bacterial persistence. Conventional antibiotics primarily act on actively growing bacteria, but they are inactive against persister cells with a slowed metabolism. Alarmone synthetase inhibitors have antipersister properties that may enhance conventional antibiotics’ antibacterial action. Two groups of RSH proteins are responsible for the synthesis of alarmones: long RelA/SpoT homologs and small alarmone synthetases. Many species of bacteria possess both types of enzymes. Despite the fact that a number of inhibitors of bifunctional long synthetases/hydrolases have been described to date, their properties with respect to monofunctional small alarmone synthetases have been studied poorly. This study investigated the effect of the alarmone synthetase inhibitor DMNP on the purified RelZ small alarmone synthetase protein from Mycolicibacterium smegmatis.
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spelling doaj.art-d1a9dc67236a4f6ab11eec2c318848aa2023-01-17T09:11:28ZengEDP SciencesBIO Web of Conferences2117-44582023-01-01570800210.1051/bioconf/20235708002bioconf_itsm2023_08002DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZSidorov Roman Yu.0Tkachenko Alexander G.1Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, the Ural Branch of Russian Academy of SciencesInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, the Ural Branch of Russian Academy of SciencesSuppression of the stringent response is a promising strategy for the treatment of persistent bacterial infections. A novel class of compounds having a mechanism of action based on alarmone synthetase inhibition and suppressing the synthesis of (p)ppGpp alarmones in bacteria may provide a more effective treatment for latent infections and resolve problems associated with bacterial persistence. Conventional antibiotics primarily act on actively growing bacteria, but they are inactive against persister cells with a slowed metabolism. Alarmone synthetase inhibitors have antipersister properties that may enhance conventional antibiotics’ antibacterial action. Two groups of RSH proteins are responsible for the synthesis of alarmones: long RelA/SpoT homologs and small alarmone synthetases. Many species of bacteria possess both types of enzymes. Despite the fact that a number of inhibitors of bifunctional long synthetases/hydrolases have been described to date, their properties with respect to monofunctional small alarmone synthetases have been studied poorly. This study investigated the effect of the alarmone synthetase inhibitor DMNP on the purified RelZ small alarmone synthetase protein from Mycolicibacterium smegmatis.https://www.bio-conferences.org/articles/bioconf/pdf/2023/02/bioconf_itsm2023_08002.pdf
spellingShingle Sidorov Roman Yu.
Tkachenko Alexander G.
DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
BIO Web of Conferences
title DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
title_full DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
title_fullStr DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
title_full_unstemmed DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
title_short DMNP, a Synthetic Analog of Erogorgiaene, Inhibits the ppGpp Synthetase Activity of the Small Alarmone Synthetase RelZ
title_sort dmnp a synthetic analog of erogorgiaene inhibits the ppgpp synthetase activity of the small alarmone synthetase relz
url https://www.bio-conferences.org/articles/bioconf/pdf/2023/02/bioconf_itsm2023_08002.pdf
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