Synergistic Interaction of Certain Essential Oils and Their Active Compounds with Fluconazole against Azole-resistant Strains of Cryptococcus neoformans.

Mohd Sajjad Ahmad Khan
Author Information
  1. Mohd Sajjad Ahmad Khan: Department of Basic Sciences, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Abstract

OBJECTIVES: This study investigated the anti-cryptococcal potential of certain essential oils (EOs)/compounds alone and in combination with fluconazole.
MATERIALS AND METHODS: We investigated the antifungal activity of oils of Cinnamomum verum, Cymbopogon citratus, Cymbopogon martini, and Syzygium aromaticum, and their major active ingredients cinnamaldehyde, citral, eugenol, and geraniol against clinical and standard strains of Cryptococcus neoformans (CN). Disc diffusion, broth microdilution, checkerboard methods, and transmission electron microscopy were employed to determine growth inhibition, synergistic interaction, and mechanism of action of test compounds.
RESULTS: EOs/compounds showed pronounced antifungal efficacy against azole-resistant CN in the order of cinnamaldehyde > eugenol > S. aromaticum > C. verum > citral > C. citratus > geraniol ��� C. martini, each exhibiting zone of inhibition >15 mm. These oils/compounds were highly cidal compared to fluconazole. Eugenol and cinnamaldehyde showed the strongest synergy with fluconazole against CN by lowering their MICs up to 32-fold. Transmission electron microscopy indicated damage of the fungal cell wall, cell membrane, and other endomembranous organelles.
CONCLUSION: Test oils and their active compounds exhibited potential anti-cryptococcus activity against the azole-resistant strains of CN. Moreover, eugenol and cinnamaldehyde significantly potentiated the anti-cryptococcal activity of fluconazole. It is suggested that multiple sites of action from oils/compounds could turn static fluconazole into a cidal drug combination in combating cryptococcosis.

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MeSH Term

Cryptococcus neoformans
Fluconazole
Drug Synergism
Antifungal Agents
Oils, Volatile
Microbial Sensitivity Tests
Cymbopogon
Drug Resistance, Fungal
Acrolein
Eugenol
Humans
Acyclic Monoterpenes
Syzygium
Cinnamomum zeylanicum
Terpenes
Monoterpenes
Microscopy, Electron, Transmission
Plant Oils
Cryptococcosis

Chemicals

Fluconazole
Antifungal Agents
Oils, Volatile
Acrolein
cinnamaldehyde
Eugenol
Acyclic Monoterpenes
citral
geraniol
Terpenes
Monoterpenes
Plant Oils

Word Cloud

Created with Highcharts 10.0.0>fluconazolecinnamaldehydeCNoilsactivityeugenolCinvestigatedanti-cryptococcalpotentialcombinationantifungalverumCymbopogoncitratusmartiniaromaticumactivecitralgeraniolstrainsCryptococcusneoformanselectronmicroscopyinhibitionactioncompoundsshowedazole-resistantoils/compoundscidalcellOBJECTIVES:studycertainessentialEOs/compoundsaloneMATERIALSANDMETHODS:CinnamomumSyzygiummajoringredientsclinicalstandardDiscdiffusionbrothmicrodilutioncheckerboardmethodstransmissionemployeddeterminegrowthsynergisticinteractionmechanismtestRESULTS:EOs/compoundspronouncedefficacyorderS���exhibitingzone>15mmhighlycomparedEugenolstrongestsynergyloweringMICs32-foldTransmissionindicateddamagefungalwallmembraneendomembranousorganellesCONCLUSION:Testexhibitedanti-cryptococcusMoreoversignificantlypotentiatedsuggestedmultiplesitesturnstaticdrugcombatingcryptococcosisSynergisticInteractionCertainEssentialOilsActiveCompoundsFluconazoleAzole-resistantStrains

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