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Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

作者 Tsou, Lun K.; Lara-Tejero, Maria; RoseFigura, Jordan; Zhang, Zhenrun J.; Wang, Yen-Chih; Yount, Jacob S.; Lefebre, Matthew; Dossa, Paul D.; Kato, Junya; Guan, Fulan; Lam, Wing; Cheng, Yung-Chi; Galan, Jorge E.; Hang, Howard C.

期刊 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , FEB 24 2016,7:138

DOI 10.1021/jacs.5b11575 PubMed 26847396

摘要 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. Among 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 reveal a previously unappreciated mechanism of action for anti-infective medicinal plants.

涉及物种 黄芩 Scutellaria baicalensis