Persistence and drug tolerance in pathogenic yeast

Area of Science:

• Mycology
• Infectious Diseases
• Cell Biology

Background:

• Antifungal drug tolerance in fungal pathogens is a significant clinical challenge.
• Persister cells, a subpopulation of cells with wild-type genotype, contribute to antifungal drug recalcitrance.
• Mechanisms governing fungal persister cell formation and survival are not fully understood.

Purpose of the Study:

• To review the current understanding of fungal persister cells and their role in antifungal treatment failure.
• To explore the mechanisms underlying the formation and survival of fungal persister cells.
• To propose novel therapeutic strategies targeting shared mechanisms between persister and quiescent cells.

Main Methods:

• Literature review of studies on fungal persister cells and antifungal drug tolerance.
• Analysis of cellular mechanisms contributing to persister cell phenotype, including membrane composition, stress response, and cell wall integrity.
• Investigation of the role of the TORC1 pathway in regulating fungal persistence.

Main Results:

• Fungal persister cells survive antifungal treatment without genetic mutations through altered physiology.
• Key survival mechanisms include modified membrane composition, enhanced stress responses, and improved cell wall integrity.
• Inhibition of the TORC1 pathway has been identified as an inducer of fungal persistence, suggesting a link to cell quiescence.

Conclusions:

• Fungal persister cells exhibit phenotypic traits similar to quiescent cells, residing in the G0 phase of the cell cycle.
• Shared drug-tolerance mechanisms between persister and quiescent cells offer potential therapeutic targets.
• Developing treatment strategies independent of fungal growth mode could overcome systemic fungal infections.