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

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• 作者：Lun K. Tsou ; María Lara-Tejero ; Jordan RoseFigura ; Zhenrun J. Zhang ; Yen-Chih Wang ; Jacob S. Yount ; Matthew Lefebre ; Paul D. Dossa ; Junya Kato ; Fulan Guan ; Wing Lam ; Yung-Chi Cheng ; Jorge E. Galán ; Howard C. Hang
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：February 24, 2016
• 年：2016
• 卷：138
• 期：7
• 页码：2209-2218
• 全文大小：606K
• ISSN：1520-5126

文摘

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.