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The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation

Many important bacterial pathogens are using the type III secretion system to deliver effectors into host cells. Salmonella Typhimurium (S. Typhimurium) is a pathogenic Gram-negative bacterium with the type III secretion system as its major virulence factor. Our previous studies demonstrated that th...

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Autores principales: Zhang, Yong, Liu, Yan, Luo, Jingjing, Jie, Jing, Deng, Xuming, Song, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427694/
https://www.ncbi.nlm.nih.gov/pubmed/34512322
http://dx.doi.org/10.3389/fphar.2021.674955
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author Zhang, Yong
Liu, Yan
Luo, Jingjing
Jie, Jing
Deng, Xuming
Song, Lei
author_facet Zhang, Yong
Liu, Yan
Luo, Jingjing
Jie, Jing
Deng, Xuming
Song, Lei
author_sort Zhang, Yong
collection PubMed
description Many important bacterial pathogens are using the type III secretion system to deliver effectors into host cells. Salmonella Typhimurium (S. Typhimurium) is a pathogenic Gram-negative bacterium with the type III secretion system as its major virulence factor. Our previous studies demonstrated that thymol, a monoterpene phenol derivative of cymene, inhibited S. Typhimurium invasion into mammalian cells and protected mice from infection. However, the antibacterial mechanism of thymol is not clear. In this study, we revealed that thymol interferes with the abundance of about 100 bacterial proteins through proteomic analysis. Among the 42 proteins whose abundance was reduced, 11 were important virulence factors associated with T3SS-1. Further analyses with SipA revealed that thymol directly interacts with this protein to induce conformational changes, which makes it susceptible to the Lon protease. In agreement with this observation, thymol effectively blocks cell invasion by S. Typhimurium. Thus, thymol represents a class of anti-virulence compounds that function by targeting pathogenic factors for degradation.
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spelling pubmed-84276942021-09-10 The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation Zhang, Yong Liu, Yan Luo, Jingjing Jie, Jing Deng, Xuming Song, Lei Front Pharmacol Pharmacology Many important bacterial pathogens are using the type III secretion system to deliver effectors into host cells. Salmonella Typhimurium (S. Typhimurium) is a pathogenic Gram-negative bacterium with the type III secretion system as its major virulence factor. Our previous studies demonstrated that thymol, a monoterpene phenol derivative of cymene, inhibited S. Typhimurium invasion into mammalian cells and protected mice from infection. However, the antibacterial mechanism of thymol is not clear. In this study, we revealed that thymol interferes with the abundance of about 100 bacterial proteins through proteomic analysis. Among the 42 proteins whose abundance was reduced, 11 were important virulence factors associated with T3SS-1. Further analyses with SipA revealed that thymol directly interacts with this protein to induce conformational changes, which makes it susceptible to the Lon protease. In agreement with this observation, thymol effectively blocks cell invasion by S. Typhimurium. Thus, thymol represents a class of anti-virulence compounds that function by targeting pathogenic factors for degradation. Frontiers Media S.A. 2021-08-26 /pmc/articles/PMC8427694/ /pubmed/34512322 http://dx.doi.org/10.3389/fphar.2021.674955 Text en Copyright © 2021 Zhang, Liu, Luo, Jie, Deng and Song. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Yong
Liu, Yan
Luo, Jingjing
Jie, Jing
Deng, Xuming
Song, Lei
The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title_full The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title_fullStr The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title_full_unstemmed The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title_short The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation
title_sort herbal compound thymol targets multiple salmonella typhimurium virulence factors for lon protease degradation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427694/
https://www.ncbi.nlm.nih.gov/pubmed/34512322
http://dx.doi.org/10.3389/fphar.2021.674955
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