Rosemary essential oil and its components 1,8-cineole and α-pinene induce ROS-dependent lethality and ROS-independent virulence inhibition in Candida albicans

PLoS One. 2022 Nov 16;17(11):e0277097. doi: 10.1371/journal.pone.0277097. eCollection 2022.

Abstract

The essential oil from Rosmarinus officinalis L., a composite mixture of plant-derived secondary metabolites, exhibits antifungal activity against virulent candidal species. Here we report the impact of rosemary oil and two of its components, the monoterpene α-pinene and the monoterpenoid 1,8-cineole, against Candida albicans, which induce ROS-dependent cell death at high concentrations and inhibit hyphal morphogenesis and biofilm formation at lower concentrations. The minimum inhibitory concentrations (100% inhibition) for both rosemary oil and 1,8-cineole were 4500 μg/ml and 3125 μg/ml for α-pinene, with the two components exhibiting partial synergy (FICI = 0.55 ± 0.07). At MIC and 1/2 MIC, rosemary oil and its components induced a generalized cell wall stress response, causing damage to cellular and organelle membranes, along with elevated chitin production and increased cell surface adhesion and elasticity, leading to complete vacuolar segregation, mitochondrial depolarization, elevated reactive oxygen species, microtubule dysfunction, and cell cycle arrest mainly at the G1/S phase, consequently triggering cell death. Interestingly, the same oils at lower fractional MIC (1/8-1/4) inhibited virulence traits, including reduction of mycelium (up to 2-fold) and biofilm (up to 4-fold) formation, through a ROS-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology
  • Candida albicans
  • Eucalyptol / pharmacology
  • Microbial Sensitivity Tests
  • Monoterpenes / pharmacology
  • Oils, Volatile* / pharmacology
  • Reactive Oxygen Species
  • Rosmarinus*
  • Virulence

Substances

  • rosemary oil
  • Eucalyptol
  • alpha-pinene
  • Reactive Oxygen Species
  • Oils, Volatile
  • Antifungal Agents
  • Monoterpenes

Grants and funding

This work was supported by Natural Science and Engineering Research Council Discovery Grant (NSERC DG; RGPIN-2018-06649), Saskatchewan Health Research Foundation Collaborative Innovation Development and Canada Foundation for Innovation (CFI) grants to TESD, a NSERC DG (RGPIN-2017-4799) and Canada Research Chair (950-228957) to MW. TS was partially supported by the Faculty of Science and CFI infrastructure operating fund to TESD. ZS was partially supported by the Faculty of Graduate Studies and Research at the University of Regina. There was no additional external funding received for this study.