The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in Candida albicans

Marina Druseikis, Austin Mottola, Judith Berman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)36-46
Number of pages11
JournalCurrent Clinical Microbiology Reports
Volume10
Issue number2
DOIs
StatePublished - Jun 2023

Funding

FundersFunder number
Horizon 2020 Framework Programme951475
HORIZON EUROPE European Research Council
European Research Council

    Keywords

    • Candida albicans
    • Drug resistance
    • Drug tolerance
    • Metabolism

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