Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus

Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public health. Especially the emergence of methicillin-resistant Staphylococcus aureus (MRSA) increased the diff iculty of S. aureus treatment. Staphyloxanthin is a crucial virulence factor of S. aureus. Blocking staph...

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Main Authors: Jiang Chang, Bo Chen, Zeqian Du, Bowen Zhao, Jiahui Li, Ziyi Li, Kannappan Arunachalam, Ting Shi, Dongqing Wei, Chunlei Shi
Format: Article
Language:English
Published: Tsinghua University Press 2024-05-01
Series:Food Science and Human Wellness
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Online Access:https://www.sciopen.com/article/10.26599/FSHW.2022.9250115
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author Jiang Chang
Bo Chen
Zeqian Du
Bowen Zhao
Jiahui Li
Ziyi Li
Kannappan Arunachalam
Ting Shi
Dongqing Wei
Chunlei Shi
author_facet Jiang Chang
Bo Chen
Zeqian Du
Bowen Zhao
Jiahui Li
Ziyi Li
Kannappan Arunachalam
Ting Shi
Dongqing Wei
Chunlei Shi
author_sort Jiang Chang
collection DOAJ
description Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public health. Especially the emergence of methicillin-resistant Staphylococcus aureus (MRSA) increased the diff iculty of S. aureus treatment. Staphyloxanthin is a crucial virulence factor of S. aureus. Blocking staphyloxanthin production could help the host immune system counteract the invading S. aureus cells. In this study, we first screened for staphyloxanthin inhibitors using a virtual screening method. The outcome of the virtual screening method resulted in the identification of eugenol (300 μg/mL), which significantly inhibits the staphyloxanthin production in S. aureus ATCC 29213, S. aureus Newman, MRSA ATCC 43300 and MRSA ATCC BAA1717 by 84.2%, 63.5%, 68.1%, and 79.5%, respectively. The outcome of the growth curve assay, f ield-emission scanning electron, and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of S. aureus. Moreover, the survival rate of S. aureus ATCC 29213 and MRSA ATCC 43300 under H2O2 pressure decreased to 51.9% and 45.5% in the presence of eugenol, respectively. The quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM enzyme. Taken together, we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat S. aureus especially MRSA infections.
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spelling doaj-art-034aae2db03143d99c8a1c8be26e52792025-01-10T06:54:23ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-05-011331368137710.26599/FSHW.2022.9250115Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureusJiang Chang0Bo Chen1Zeqian Du2Bowen Zhao3Jiahui Li4Ziyi Li5Kannappan Arunachalam6Ting Shi7Dongqing Wei8Chunlei Shi9MOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaMOST-USDA Joint Research Center for Food Safety, School of Agriculture and Biology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, ChinaStaphylococcus aureus is a serious foodborne pathogen threatening food safety and public health. Especially the emergence of methicillin-resistant Staphylococcus aureus (MRSA) increased the diff iculty of S. aureus treatment. Staphyloxanthin is a crucial virulence factor of S. aureus. Blocking staphyloxanthin production could help the host immune system counteract the invading S. aureus cells. In this study, we first screened for staphyloxanthin inhibitors using a virtual screening method. The outcome of the virtual screening method resulted in the identification of eugenol (300 μg/mL), which significantly inhibits the staphyloxanthin production in S. aureus ATCC 29213, S. aureus Newman, MRSA ATCC 43300 and MRSA ATCC BAA1717 by 84.2%, 63.5%, 68.1%, and 79.5%, respectively. The outcome of the growth curve assay, f ield-emission scanning electron, and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of S. aureus. Moreover, the survival rate of S. aureus ATCC 29213 and MRSA ATCC 43300 under H2O2 pressure decreased to 51.9% and 45.5% in the presence of eugenol, respectively. The quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM enzyme. Taken together, we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat S. aureus especially MRSA infections.https://www.sciopen.com/article/10.26599/FSHW.2022.9250115staphylococcus aureusstaphyloxanthineugenolvirtual screening4,4’-diapophytoene synthase (crtm)
spellingShingle Jiang Chang
Bo Chen
Zeqian Du
Bowen Zhao
Jiahui Li
Ziyi Li
Kannappan Arunachalam
Ting Shi
Dongqing Wei
Chunlei Shi
Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
Food Science and Human Wellness
staphylococcus aureus
staphyloxanthin
eugenol
virtual screening
4,4’-diapophytoene synthase (crtm)
title Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
title_full Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
title_fullStr Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
title_full_unstemmed Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
title_short Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus
title_sort eugenol targeting crtm inhibits the biosynthesis of staphyloxanthin in staphylococcus aureus
topic staphylococcus aureus
staphyloxanthin
eugenol
virtual screening
4,4’-diapophytoene synthase (crtm)
url https://www.sciopen.com/article/10.26599/FSHW.2022.9250115
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