title: Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates.
abstract: 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.
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.|Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes , Zhunan Town, Miaoli County 35053, Taiwan, R.O.C.
authors: Lun K
authors: LK
authors: Tsou
authors: Department of Microbial Pathogenesis, Yale University School of Medicine , New Haven, Connecticut 06536, United States.
authors: María
authors: M
authors: Lara-Tejero
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Jordan
authors: J
authors: RoseFigura
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Zhenrun J
authors: ZJ
authors: Zhang
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Yen-Chih
authors: YC
authors: Wang
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Jacob S
authors: JS
authors: Yount
authors: Department of Microbial Pathogenesis, Yale University School of Medicine , New Haven, Connecticut 06536, United States.
authors: Matthew
authors: M
authors: Lefebre
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Paul D
authors: PD
authors: Dossa
authors: Department of Microbial Pathogenesis, Yale University School of Medicine , New Haven, Connecticut 06536, United States.
authors: Junya
authors: J
authors: Kato
authors: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
authors: Fulan
authors: F
authors: Guan
authors: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
authors: Wing
authors: W
authors: Lam
authors: Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
authors: Yung-Chi
authors: YC
authors: Cheng
authors: Department of Microbial Pathogenesis, Yale University School of Medicine , New Haven, Connecticut 06536, United States.
authors: Jorge E
authors: JE
authors: Galán
authors: Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University , New York, New York 10065, United States.
authors: Howard C
authors: HC
authors: Hang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000069296:Type III Secretion Systems / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D000069296:Type III Secretion Systems