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Updated: Aug 5, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in Candida albicans
Marina Druseikis1, Austin Mottola1, Judith Berman1
1Shmunis School of Biomedical and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Purpose Of Review:
Failure of antifungal treatment is alarmingly common in patients infected with Candida albicans isolates that test as susceptible in vitro. This means that clinical susceptibility tests have limited predictive value for treatment success. To guide the improvement of patient outcomes, we must understand the effects of environmental and metabolic states on drug responses.
Recent Findings:
Lab conditions often deviate from host environments, and current susceptibility testing standards ignore slow-growing, tolerant phenotypes; both factors may contribute to antifungal treatment failure. Metabolomic studies reveal that strain background, nutrient availability, and drug exposure influence the metabolic state of C. albicans cells; similarly, the metabolic state influences drug susceptibility.
Summary:
Identifying tolerant strains in the clinic may improve patient outcomes. Studies that analyze the effects of essential but limited nutrients have the potential to improve the avoidance of persistent candidiasis and to reduce the frequency of antifungal treatment failures. Here, we highlight literature that explores the effect of drug exposure and antifungal drug resistance status on the C. albicans metabolome. Similar analyses need to be carried out relative to antifungal drug tolerance. Additionally, we focus on the biological relevance of four essential small molecules-iron, zinc, phosphate, and sphingolipids-to antifungal tolerance and resistance.
Insights
Antifungal treatment failure is common, even with susceptible Candida albicans. Understanding how metabolic states and nutrient availability affect drug response is key to improving patient outcomes and reducing treatment failures.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Metabolomics
Background:
- Antifungal treatment failure occurs despite in vitro susceptibility of Candida albicans.
- Current susceptibility tests have limited predictive value for treatment success.
- Host environments and drug responses are influenced by fungal metabolic states.
Purpose of the Study:
- To understand how environmental and metabolic states affect antifungal drug responses in Candida albicans.
- To guide improvements in antifungal treatment strategies.
- To identify factors contributing to antifungal treatment failure.
Main Methods:
- Literature review focusing on metabolomic studies of Candida albicans.
- Analysis of the effects of nutrient availability and drug exposure on fungal metabolism.
- Examination of the role of essential small molecules (iron, zinc, phosphate, sphingolipids) in antifungal tolerance and resistance.
Main Results:
- Metabolomic studies show that strain background, nutrients, and drug exposure alter the metabolic state of C. albicans.
- The metabolic state of C. albicans influences its susceptibility to antifungal drugs.
- Limited nutrients and specific metabolic states may promote antifungal tolerance.
Conclusions:
- Identifying tolerant Candida albicans strains in clinical settings is crucial for improving patient outcomes.
- Further research into the impact of essential nutrients on antifungal tolerance is needed.
- Understanding the interplay between metabolism, drug exposure, and antifungal tolerance/resistance is vital for reducing treatment failures.
