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Protocols for Measuring Tolerant and Heteroresistant Drug Responses of Pathogenic Yeasts
1Shmunis School of Biomedical and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Abstract:
The classic definition of antimicrobial susceptibility to antifungal drugs ignores the persistence of subpopulations that survive in the presence of a drug. Even in entirely clonal populations, small subpopulations of yeast can grow in the presence of a drug, sometimes up to extremely high drug concentrations, such that they may be clinically relevant. Identifying and quantifying the incidence with which these subpopulations arise is an essential step in understanding how pathogenic yeast, such as Candida species (i.e., C. albicans, C. glabrata, C. auris, C. tropicalis, C. parapsilosis, and others) as well as Cryptococcus species, behave in response to antifungal therapeutics. Here we describe simple in vitro protocols for the quantification of drug responses with subpopulation resolution.
Insights
Antifungal drug susceptibility testing often overlooks surviving yeast subpopulations. New in vitro methods quantify these persistent cells, crucial for understanding drug resistance in pathogenic fungi like Candida.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Yeast Pathogenesis
Background:
- Standard antifungal susceptibility testing (AST) does not account for drug-tolerant subpopulations.
- These persistent subpopulations can survive high drug concentrations and have clinical relevance.
- Understanding their emergence is key to managing infections caused by pathogenic yeasts.
Purpose of the Study:
- To develop and present simple in vitro protocols for quantifying antifungal drug responses.
- To enable subpopulation-level analysis of yeast drug tolerance.
- To improve the understanding of pathogenic yeast behavior under antifungal pressure.
Main Methods:
- Development of simple in vitro protocols.
- Quantification of drug responses at the subpopulation level.
- Application to pathogenic yeast species, including Candida and Cryptococcus.
Main Results:
- Protocols allow for the identification and quantification of drug-tolerant yeast subpopulations.
- Demonstration of subpopulation survival even at high antifungal concentrations.
- Provides a method to assess the incidence of drug-tolerant subpopulations.
Conclusions:
- The described methods offer subpopulation resolution in antifungal drug response assays.
- This approach is essential for a comprehensive understanding of antifungal drug efficacy.
- Accurate assessment of drug-tolerant subpopulations is vital for clinical treatment strategies against yeast infections.
