Geraniol eradicates Candida glabrata biofilm by targeting multiple cellular pathways

Area of Science:

• Mycology
• Pharmacology
• Biochemistry

Background:

• Fungal infections, particularly from drug-resistant Candida glabrata, pose a significant global health challenge.
• Novel therapeutic interventions are urgently needed to combat the rising burden of fungal diseases.

Purpose of the Study:

• To evaluate the antifungal activity and mode of action of geraniol (GR), a monoterpene phytoactive molecule, against Candida glabrata biofilms.
• To explore GR's potential as a novel therapeutic agent against C. glabrata.

Main Methods:

• Assessed GR's inhibitory and eradication effects on planktonic and biofilm growth of C. glabrata clinical isolates.
• Investigated GR's impact on extracellular matrix components (carbohydrates, eDNA, enzymes) and cell wall integrity (chitin, β-glucan).
• Analyzed effects on cell membrane ergosterol, drug efflux pumps (CDR1, ERG4), mitochondrial activity, calcium uptake, and cell cycle progression using microscopy, spectroscopy, and RT-PCR.

Main Results:

• GR inhibited planktonic and sessile growth and eradicated mature C. glabrata biofilms.
• GR reduced extracellular matrix content and enzyme activity, targeted cell wall chitin and β-glucan, and decreased ergosterol levels.
• GR blocked ABC drug efflux pumps, altered mitochondrial function, increased calcium uptake, induced apoptosis via cytochrome C release, and arrested the cell cycle.

Conclusions:

• Geraniol demonstrates potent antifungal activity against Candida glabrata, including clinical isolates.
• GR acts through multiple mechanisms, including cell wall and membrane disruption, efflux pump inhibition, and induction of apoptosis.
• Geraniol shows significant promise as a novel therapeutic agent for treating C. glabrata infections.