Long-term stability of acquired drug resistance and resistance associated mutations in the fungal pathogen Nakaseomyces glabratus (Candida glabrata)

The increasing number of fungal isolates showing drug or multidrug resistance poses a significant medical threat. Several yeast pathogens, like Nakaseomyces glabratus, can develop drug resistance through genetic mutations. The stability of acquired drug resistance is crucial for understanding the appearance and spread of drug-resistant outbreaks and defining effective strategies. An in vitro evolution approach was used to assess the stability of resistance phenotypes and mutations acquired from antifungal exposure. Results showed remarkable stability in several evolved populations, with anidulafungin resistance showing higher stability than fluconazole resistance. Novel mutations in previously altered resistance-associated genes were detected, suggesting a possible compensatory role. Acquired resistance, particularly to anidulafungin, is a long-lasting phenotype with significant implications for drug-resistant clinical outbreaks.