Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro

PLoS One. 2016 Apr 29;11(4):e0153468. doi: 10.1371/journal.pone.0153468. eCollection 2016.

Abstract

Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Bacterial Load
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Drug Synergism
  • Flavanones / administration & dosage
  • Flavanones / pharmacology*
  • Genes, Bacterial
  • Humans
  • In Vitro Techniques
  • Quorum Sensing / drug effects
  • Quorum Sensing / genetics
  • Quorum Sensing / physiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / physiology
  • Virulence / drug effects

Substances

  • Anti-Bacterial Agents
  • Flavanones
  • baicalein

Grant support

All sources of funding are from the National Natural Science Foundation of China (Grant Number: 81060002; website: http://www.nsfc.gov.cn/). The author Yiqiang Chen received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.