Antifungal tolerance and resistance dynamics depend on infection load, drug treatment, and host innate immunity

Abstract

Fungi contribute substantially to the global antimicrobial resistance crisis. Tolerance is a novel form of antifungal resistance in which fungal pathogens emerge, grow slowly, and survive antifungal drug treatment. We quantitatively model the population and evolutionary dynamics of a multidrug resistant pathogen Candidozyma auris (formerly Candida auris) infecting an invertebrate host (Galleria mellonella) with an innate immune system. We find that the establishment, dominance, and co-existence of tolerant and resistant subpopulations depend on infection load, drug-treatment, and innate host immunity. This study enhances our understanding of the population and evolutionary dynamics of pathogenic infections and provides a quantitative framework to predict antimicrobial resistance.