Evolution of drug resistance in an antifungal-naive chronic Candida lusitaniae infection

Significance Drug-resistant subpopulations of microbes or tumor cells are difficult to detect but can confound disease treatment. In this deep characterization of a chronic fungal infection, we report unprecedented heterogeneity in the drug resistance-related gene MRR1 among Clavispora ( Candida ) lusitaniae isolates from a single individual. Cells expressing Mrr1 variants that led to drug resistance, by elevated expression of the MDR1 -encoded efflux protein, were present at low levels in each sample and thus were undetected in standard assays. We provide evidence that these drug-resistant fungi may arise indirectly in response to other factors present in the infection. Our work suggests that alternative methods may be able to identify drug-resistant subpopulations and thus positively impact patient care.