Dose-dependent antifungal drug tolerance

Antimicrobial resistance is a global health problem, with drug-resistant fungi posing major challenges for the treatment of immunocompromised patients. Antifungal tolerance is a recently discovered phenomenon whereby pathogenic fungi, including the multidrug-resistant pathogenic yeast Candidozyma (Candida) auris, grow slowly above minimum inhibitory drug concentrations [1]. We combine physics-based spatiotemporal models with microbiology experiments to quantitatively investigate the emergence of tolerance to all three major classes of antifungal drugs in C. auris [2]. Specifically, we solve Fick’s second law with a finite difference method to simulate drug diffusion combined with experimental disk diffusion assays to determine the concentrations at which antifungal-tolerant C. auris colonies emerge. Our study advances antimicrobial resistance research by providing a method to quantify antifungal tolerance and by demonstrating that tolerance is a dose-dependent phenomenon in a multidrug-resistant fungal pathogen.

[1] S. Rasouli Koohi, S.A. Shankarnarayan, C.M. Galon, D.A. Charlebois, Biomedicines, 11: 898 (2023)

[2] S. Rasouli Koohi and D.A. Charlebois, bioRxiv, doi.org/10.1101/2025.09.05.674536 (2025).