Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins
Abstract Salmonella Typhimurium (S. Typhimurium, ST) is a food-borne pathogen that can be transmitted from animals to humans and causes symptoms such as diarrhea, fever, and vomiting. While antibiotics are commonly used to treat clinical infections, the increase in drug resistance has limited their...
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Nature Portfolio
2025-02-01
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| author | Zhenxu Shi Zhimin Guo Siqi Li Chenxiao Jiang Jianfeng Wang Xuming Deng Hongtao Liu Jiazhang Qiu |
| author_facet | Zhenxu Shi Zhimin Guo Siqi Li Chenxiao Jiang Jianfeng Wang Xuming Deng Hongtao Liu Jiazhang Qiu |
| author_sort | Zhenxu Shi |
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| description | Abstract Salmonella Typhimurium (S. Typhimurium, ST) is a food-borne pathogen that can be transmitted from animals to humans and causes symptoms such as diarrhea, fever, and vomiting. While antibiotics are commonly used to treat clinical infections, the increase in drug resistance has limited their effectiveness. Antivirulence drugs offer a new approach to treating bacterial infections by targeting specific virulence factors without affecting bacterial growth, thus helping to combat infection without exerting selective pressure on bacteria or inducing resistance. Salmonella pathogenicity island 1 (SPI-1), encoding type three secretion system 1 (T3SS-1), serves as a crucial virulence factor for the invasion of ST into host cells, making it an ideal target for screening anti-Salmonella virulence drugs. This project involved screening of ST invasion inhibitors through a gentamicin protection assay and identified purpurin (PPR) as capable of inhibiting the ST invasion of HeLa cells. Subsequent studies revealed that PPR had no effect on the natural growth of bacteria and was not cytotoxic to host cells. A mechanistic study revealed that PPR effectively inhibits the secretion of T3SS-1 in ST. The results from animal experiments indicated that PPR exhibited significant efficacy in a mouse enteritis model caused by ST infection, increasing the survival rate of mice infected with a lethal dose by 50%, reducing spleen colonization in infected mice, and alleviating tissue damage resulting from ST infection. Therefore, PPR represents a promising antivirulence drug that targets the T3SS of ST and may serve as a hit compound for the development of novel antivirulence drugs for the treatment of ST. |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
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| spelling | doaj-art-d43d1b873e2d4adda7433f5a3c10d08d2025-02-09T12:37:36ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-86822-1Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteinsZhenxu Shi0Zhimin Guo1Siqi Li2Chenxiao Jiang3Jianfeng Wang4Xuming Deng5Hongtao Liu6Jiazhang Qiu7State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University; Department of Laboratory Medicine, Center for Infectious Diseases and Pathogen Biology, The First Hospital of Jilin UniversityAbstract Salmonella Typhimurium (S. Typhimurium, ST) is a food-borne pathogen that can be transmitted from animals to humans and causes symptoms such as diarrhea, fever, and vomiting. While antibiotics are commonly used to treat clinical infections, the increase in drug resistance has limited their effectiveness. Antivirulence drugs offer a new approach to treating bacterial infections by targeting specific virulence factors without affecting bacterial growth, thus helping to combat infection without exerting selective pressure on bacteria or inducing resistance. Salmonella pathogenicity island 1 (SPI-1), encoding type three secretion system 1 (T3SS-1), serves as a crucial virulence factor for the invasion of ST into host cells, making it an ideal target for screening anti-Salmonella virulence drugs. This project involved screening of ST invasion inhibitors through a gentamicin protection assay and identified purpurin (PPR) as capable of inhibiting the ST invasion of HeLa cells. Subsequent studies revealed that PPR had no effect on the natural growth of bacteria and was not cytotoxic to host cells. A mechanistic study revealed that PPR effectively inhibits the secretion of T3SS-1 in ST. The results from animal experiments indicated that PPR exhibited significant efficacy in a mouse enteritis model caused by ST infection, increasing the survival rate of mice infected with a lethal dose by 50%, reducing spleen colonization in infected mice, and alleviating tissue damage resulting from ST infection. Therefore, PPR represents a promising antivirulence drug that targets the T3SS of ST and may serve as a hit compound for the development of novel antivirulence drugs for the treatment of ST.https://doi.org/10.1038/s41598-025-86822-1SalmonellaAnti-virulenceT3SSPurpurin |
| spellingShingle | Zhenxu Shi Zhimin Guo Siqi Li Chenxiao Jiang Jianfeng Wang Xuming Deng Hongtao Liu Jiazhang Qiu Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins Scientific Reports Salmonella Anti-virulence T3SS Purpurin |
| title | Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins |
| title_full | Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins |
| title_fullStr | Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins |
| title_full_unstemmed | Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins |
| title_short | Purpurin suppresses Salmonella invasion of host cells by reducing the secretion of T3SS-1 effector proteins |
| title_sort | purpurin suppresses salmonella invasion of host cells by reducing the secretion of t3ss 1 effector proteins |
| topic | Salmonella Anti-virulence T3SS Purpurin |
| url | https://doi.org/10.1038/s41598-025-86822-1 |
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