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

J Am Chem Soc. 2016 Feb 24;138(7):2209-18. doi: 10.1021/jacs.5b11575. Epub 2016 Feb 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • High-Throughput Screening Assays
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Plants, Medicinal / chemistry*
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Type III Secretion Systems / metabolism*


  • Anti-Bacterial Agents
  • Drugs, Chinese Herbal
  • Flavonoids
  • Type III Secretion Systems