Baicalin protects mice from Staphylococcus aureus pneumonia via inhibition of the cytolytic activity of α-hemolysin

J Infect Dis. 2012 Jul 15;206(2):292-301. doi: 10.1093/infdis/jis336. Epub 2012 May 2.


α-Hemolysin (Hla) is a self-assembling, channel-forming toxin that is secreted by Staphylococcus aureus and is central to the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections in animal models. In this study, we report that baicalin (BAI), a natural compound that lacks anti-S. aureus activity, could inhibit the hemolytic activity of Hla. Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that BAI binds to the binding sites of Y148, P151, and F153 in the Hla. This binding interaction inhibits heptamer formation. Furthermore, when added to S. aureus cultures, BAI prevents Hla-mediated human alveolar epithelial (A549) cell injury. In vivo studies further demonstrated that BAI protects mice from S. aureus pneumonia. These findings indicate that BAI hinders the cell lysis activity of Hla through a novel mechanism of interrupting the formation of heptamer, which may lead to the development of novel therapeutics that aim against S. aureus Hla.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology*
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / metabolism
  • Binding Sites
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Bacterial / physiology
  • Hemolysin Proteins / antagonists & inhibitors*
  • Hemolysin Proteins / metabolism
  • Hemolysis / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia, Staphylococcal / prevention & control*
  • Protein Binding
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism
  • Structure-Activity Relationship


  • Anti-Infective Agents
  • Bacterial Toxins
  • Flavonoids
  • Hemolysin Proteins
  • staphylococcal alpha-toxin
  • baicalin