Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation

PLoS One. 2012;7(10):e47255. doi: 10.1371/journal.pone.0047255. Epub 2012 Oct 15.


Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of anti-virulence compounds could be a starting point for development of novel anti-microbial agents against S. aureus.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology
  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Gene Expression Regulation, Bacterial / drug effects*
  • Humans
  • Methicillin Resistance / genetics
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Microbial Sensitivity Tests
  • Quinazolines / chemical synthesis
  • Quinazolines / pharmacology*
  • Small Molecule Libraries
  • Streptokinase / antagonists & inhibitors*
  • Streptokinase / genetics


  • Anti-Bacterial Agents
  • CCG-2979
  • Quinazolines
  • Small Molecule Libraries
  • Streptokinase