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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Attenuation of Candida albicans virulence with focus on disruption of its vacuole functions
1Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Abstract:
The objective of the present review is to discuss if the yeast vacuole can be used as a target for attenuation of Candida albicans virulence. Literature searches were made electronically using predetermined inclusion criteria. The main searches were made through a systematic strategy in PubMed and authoritative journals in microbiology. It appeared that C. albicans virulence may be reduced by inhibiting vacuolar proton-translocating ATPase (V-ATPase) functions and acidification of the yeast vacuole by V-ATPase inhibitors, by seeking the synergistic effect of antifungals and non-antifungals affecting yeast vacuolar functions, and by inhibiting filament production - also regulated by the vacuole. Accordingly, we may impair C. albicans virulence by inhibiting functions of its vacuole, which plays essential roles during colonization and invasion of the host. Except for drugs where indications for clinical use can be redefined, such interventions may be closer to theory than to reality at the moment. But since the yeast is so difficult to eradicate by antifungal treatment, it could be rewarding to seek new strategies for reducing its virulence rather than trying to eradicate it completely from the microbiota, which often turns out to be impossible.
Insights
Targeting the yeast vacuole could reduce Candida albicans virulence. Inhibiting vacuolar functions, like proton-translocating ATPase (V-ATPase), offers a promising strategy against this difficult-to-treat fungal pathogen.
Area of Science:
- Medical Microbiology
- Mycology
- Infectious Diseases
Background:
- Candida albicans is an opportunistic fungal pathogen responsible for a range of infections, from superficial to life-threatening systemic diseases.
- Current antifungal treatments face challenges due to emerging resistance and difficulties in complete eradication, often necessitating lifelong management.
- The yeast vacuole plays critical roles in cellular homeostasis, stress response, and virulence factor regulation in C. albicans.
Purpose of the Study:
- To review the potential of the yeast vacuole as a therapeutic target for attenuating Candida albicans virulence.
- To explore novel strategies for managing C. albicans infections by targeting vacuolar functions.
Main Methods:
- Systematic literature search conducted in PubMed and leading microbiology journals.
- Inclusion criteria were predetermined to ensure a focused review of relevant studies.
- Analysis of research on inhibiting vacuolar proton-translocating ATPase (V-ATPase) and its impact on C. albicans.
Main Results:
- Inhibiting vacuolar proton-translocating ATPase (V-ATPase) function and yeast vacuole acidification can reduce C. albicans virulence.
- Synergistic effects observed with combined antifungal and non-antifungal agents targeting vacuolar functions.
- Inhibition of filament production, regulated by the vacuole, also shows potential for virulence attenuation.
Conclusions:
- The yeast vacuole is a viable target for impairing Candida albicans virulence during host colonization and invasion.
- While some interventions are theoretical, targeting vacuolar functions offers a promising alternative to complete eradication, especially for recalcitrant infections.
- Further research into redefining drug indications and developing novel vacuole-targeting strategies is warranted.
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