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

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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.

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Funding

This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 951475).

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  1. Marina Druseikis and Austin Mottola contributed equally to this work.

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  1. Shmunis School of Biomedical and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Marina Druseikis, Austin Mottola & Judith Berman

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  1. Marina Druseikis
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Correspondence to Judith Berman.

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Druseikis, M., Mottola, A. & Berman, J. The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in Candida albicans. Curr Clin Micro Rpt 10, 36–46 (2023). https://doi.org/10.1007/s40588-023-00189-3

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