Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance....

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Autores principales:	Valeria Iobbi, Paola Brun, Giulia Bernabé, Roméo Arago Dougué Kentsop, Giuliana Donadio, Barbara Ruffoni, Paola Fossa, Angela Bisio, Nunziatina De Tommasi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	quorum sensing inhibitors sclareol manool <i>Salvia tingitana</i> molecular docking callus Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/9a27fe9ae5644f3a8fce8919ad19f9d9
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spelling	oai:doaj.org-article:9a27fe9ae5644f3a8fce8919ad19f9d92021-11-11T18:38:17ZLabdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>10.3390/molecules262166811420-3049https://doaj.org/article/9a27fe9ae5644f3a8fce8919ad19f9d92021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6681https://doaj.org/toc/1420-3049Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (<b>1</b>) and manool (<b>2</b>) extracted from <i>Salvia tingitana</i> were considered as potential QSI against methicillin-resistant <i>Staphylococcus aureus</i>. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of <i>S. tingitana</i> showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in <i>Salvia</i> species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in <i>Salvia</i>. Docking simulations suggested that <b>1</b> and <b>2</b> bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.Valeria IobbiPaola BrunGiulia BernabéRoméo Arago Dougué KentsopGiuliana DonadioBarbara RuffoniPaola FossaAngela BisioNunziatina De TommasiMDPI AGarticlequorum sensing inhibitorssclareolmanool<i>Salvia tingitana</i>molecular dockingcallusOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6681, p 6681 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	quorum sensing inhibitors sclareol manool <i>Salvia tingitana</i> molecular docking callus Organic chemistry QD241-441
spellingShingle	quorum sensing inhibitors sclareol manool <i>Salvia tingitana</i> molecular docking callus Organic chemistry QD241-441 Valeria Iobbi Paola Brun Giulia Bernabé Roméo Arago Dougué Kentsop Giuliana Donadio Barbara Ruffoni Paola Fossa Angela Bisio Nunziatina De Tommasi Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
description	Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (<b>1</b>) and manool (<b>2</b>) extracted from <i>Salvia tingitana</i> were considered as potential QSI against methicillin-resistant <i>Staphylococcus aureus</i>. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of <i>S. tingitana</i> showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in <i>Salvia</i> species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in <i>Salvia</i>. Docking simulations suggested that <b>1</b> and <b>2</b> bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes.
format	article
author	Valeria Iobbi Paola Brun Giulia Bernabé Roméo Arago Dougué Kentsop Giuliana Donadio Barbara Ruffoni Paola Fossa Angela Bisio Nunziatina De Tommasi
author_facet	Valeria Iobbi Paola Brun Giulia Bernabé Roméo Arago Dougué Kentsop Giuliana Donadio Barbara Ruffoni Paola Fossa Angela Bisio Nunziatina De Tommasi
author_sort	Valeria Iobbi
title	Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
title_short	Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
title_full	Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
title_fullStr	Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
title_full_unstemmed	Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>
title_sort	labdane diterpenoids from <i>salvia tingitana</i> etl. synergize with clindamycin against methicillin-resistant <i>staphylococcus aureus</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9a27fe9ae5644f3a8fce8919ad19f9d9
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Labdane Diterpenoids from <i>Salvia tingitana</i> Etl. Synergize with Clindamycin against Methicillin-Resistant <i>Staphylococcus aureus</i>

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