Menthol diminishes Staphylococcus aureus virulence-associated extracellular proteins expression

Appl Microbiol Biotechnol. 2011 Apr;90(2):705-12. doi: 10.1007/s00253-011-3122-9. Epub 2011 Feb 2.


Staphylococcus aureus is a significant human pathogen that is the major cause of a broad spectrum of illnesses, ranging from minor skin infections to life-threatening deep tissue infections and toxinosis. The ability of the organism to cause such a broad range of infections is, to a great extent, attributed to the secretion of a myriad of virulence-related extracellular proteins. Therefore, virulence as a target for antimicrobial chemotherapy has gained great interest. Menthol is a monocyclic terpene alcohol that occurs naturally in plants of the Mentha species lacking anti-S. aureus activity. In this paper, we demonstrate via hemolytic activity assays, tumor necrosis factor release assays, Western blot assays, and real-time reverse transcription-PCR assays that low concentrations of menthol can markedly inhibit the expression of α-hemolysin, enterotoxins A and B, and toxic shock syndrome toxin 1 in S. aureus. Our results indicate that menthol may be useful in managing S. aureus infections when used in combination with β-lactam antibiotics, which can often increase S. aureus toxin secretion when used at subinhibitory concentrations. In addition, the menthol basic structure has potential applications in the development of new anti-virulence drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Toxins / antagonists & inhibitors
  • Enterotoxins / antagonists & inhibitors
  • Enterotoxins / metabolism
  • Hemolysin Proteins / antagonists & inhibitors
  • Hemolysis
  • Male
  • Menthol / metabolism*
  • Menthol / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Mice
  • Mice, Inbred BALB C
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superantigens
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism
  • Virulence


  • Anti-Bacterial Agents
  • Bacterial Toxins
  • Enterotoxins
  • Hemolysin Proteins
  • Superantigens
  • Tumor Necrosis Factor-alpha
  • enterotoxin F, Staphylococcal
  • staphylococcal alpha-toxin
  • Menthol
  • enterotoxin A, Staphylococcal
  • enterotoxin B, staphylococcal