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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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.674955/full |
| _version_ | 1818724575782895616 |
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| author | Yong Zhang Yong Zhang Yan Liu Jingjing Luo Jing Jie Xuming Deng Lei Song |
| author_facet | Yong Zhang Yong Zhang Yan Liu Jingjing Luo Jing Jie Xuming Deng Lei Song |
| author_sort | Yong Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T21:28:36Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T21:28:36Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-ae1538710fa443f98ef60b6f3fcb42c12022-12-21T21:31:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.674955674955The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease DegradationYong Zhang0Yong Zhang1Yan Liu2Jingjing Luo3Jing Jie4Xuming Deng5Lei Song6Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaMany 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.674955/fulltype III secretionSalmonellaanti-virulencenatural compoundsthymol |
| spellingShingle | Yong Zhang Yong Zhang Yan Liu Jingjing Luo Jing Jie Xuming Deng Lei Song The Herbal Compound Thymol Targets Multiple Salmonella Typhimurium Virulence Factors for Lon Protease Degradation Frontiers in Pharmacology type III secretion Salmonella anti-virulence natural compounds thymol |
| 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 | type III secretion Salmonella anti-virulence natural compounds thymol |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.674955/full |
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