Tolerance of Pseudomonas aeruginosa to Melaleuca alternifolia (tea tree) oil is associated with the outer membrane and energy-dependent cellular processes

J Antimicrob Chemother. 2004 Aug;54(2):386-92. doi: 10.1093/jac/dkh359. Epub 2004 Jul 14.


Objectives: The essential oil of Melaleuca alternifolia (tea tree oil) and its components have antimicrobial activity against a wide range of Gram-positive and Gram-negative bacteria, fungi and viruses. The mechanism(s) by which Pseudomonas aeruginosa NCTC 10662 maintains a decreased susceptibility to tea tree oil and components was investigated.

Results: Ethylene diamine tetraacetic acid enhanced the antimicrobial activity of tea tree oil and terpinen-4-ol against stationary phase P. aeruginosa while polymyxin B nonapeptide enhanced the activity of tea tree oil and gamma-terpinene. Pre-treatment with the protonophore carbonyl cyanide m-chlorophenylhydrazone increased the susceptibility of exponential phase cells to sub-inhibitory concentrations of tea tree oil, terpinen-4-ol and gamma-terpinene, indicating that intrinsic tolerance to tea tree oil and components is substantially energy dependent.

Conclusions: Increased tolerance to tea tree oil in P. aeruginosa is directly related to the barrier and energy functions of the outer membrane, and may involve efflux systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents, Local / pharmacology*
  • Bacterial Outer Membrane Proteins / drug effects*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology
  • Drug Resistance, Bacterial
  • Edetic Acid / pharmacology
  • Energy Metabolism / drug effects*
  • Microscopy, Electron
  • Polymyxin B / analogs & derivatives*
  • Polymyxin B / pharmacology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / ultrastructure
  • Tea Tree Oil / pharmacology*
  • Time Factors
  • Uncoupling Agents / pharmacology


  • Anti-Infective Agents
  • Anti-Infective Agents, Local
  • Bacterial Outer Membrane Proteins
  • Uncoupling Agents
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • Tea Tree Oil
  • polymyxin B nonapeptide
  • Edetic Acid
  • Polymyxin B