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Antifungal persistence: Clinical relevance and mechanisms

Summary

Some fungal infections don’t respond well to antifungal medications even though the fungi aren’t drug-resistant. This happens because a small percentage of fungal cells enter a dormant, low-energy state that protects them from being killed by the drugs. Understanding how these persistent cells survive and finding ways to target them could help prevent recurring fungal infections and improve treatment outcomes.

Background

Antifungal persistence is a phenomenon where subpopulations of fungal cells survive high concentrations of antifungal drugs without developing resistance mutations. This differs from antifungal resistance and tolerance, and may contribute to treatment failure and recurrent fungal infections in clinical settings.

Objective

This review provides a comprehensive overview of antifungal persistence covering its definition, distinctions from related concepts, detection methods, molecular mechanisms of formation, and clinical relevance with assessment of in vivo and clinical observations.

Results

Antifungal persistence is characterized by a biphasic-killing curve distinct from resistance, involves dormant cells with reduced metabolism, and is primarily associated with biofilm formation and surface adhesion. Key mechanisms include downregulation of energy metabolism, altered protein synthesis, stress response pathway activation, and enhanced antioxidant systems.

Conclusion

Antifungal persistence represents a significant clinical problem contributing to treatment failures and recurrent infections in drug-sensitive fungal strains. Future research must elucidate the molecular basis of persistence and develop targeted therapies to overcome this phenomenon and improve clinical outcomes.
  • Published in:PLoS Pathogens,
  • Study Type:Review,
  • Source: PMID: 40934262, DOI: 10.1371/journal.ppat.1013456
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