Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates
| Autor: | Howard C. Hang, Jordan RoseFigura, Wing Lam, Jorge E. Galán, Lun K. Tsou, Zhenrun J. Zhang, Yen Chih Wang, Fulan Guan, Paul D. Dossa, Junya Kato, Maria Lara-Tejero, Matthew Lefebre, Yung-Chi Cheng, Jacob S. Yount |
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| Rok vydání: | 2016 |
| Předmět: |
Salmonella typhimurium
0301 basic medicine 030106 microbiology Flavonoid Virulence Microbial Sensitivity Tests Biochemistry Article Catalysis Substrate Specificity Type three secretion system Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Colloid and Surface Chemistry Type III Secretion Systems Secretion Flavonoids chemistry.chemical_classification Plants Medicinal Dose-Response Relationship Drug Molecular Structure biology Chemistry Effector food and beverages General Chemistry biology.organism_classification Anti-Bacterial Agents High-Throughput Screening Assays Baicalein 030104 developmental biology Salmonella enterica bacteria Scutellaria baicalensis Drugs Chinese Herbal |
| Zdroj: | Journal of the American Chemical Society. 138:2209-2218 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.5b11575 |
| Popis: | Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Amongst the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveals a previously unappreciated mechanism of action for anti-infective medicinal plants. |
| Databáze: | OpenAIRE |
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