Year: 2018
Type: article
Abstract: 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.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: National Science Foundation, Cystic Fibrosis Foundation, Dartmouth College, National Institutes of Health, Audrey and Theodor Geisel School of Medicine at Dartmouth, National Heart, Lung, and Blood Institute, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1753156876, Acquisition of a Scalable Storage Cluster for Data Intensive NIH Research, G4673074763, Regional Hypoxia Impacts the Heterogeneity of Inflammatory Lung Disease, MRI: Acquisition of a Big Data Compute Cluster for Interdisciplinary Research, Cellular and Molecular Mechanisms of Lung Disease, G6283561996, G6487998818, Molecular and Cellular Biology at Dartmouth, Dynamics of Bacterial-Fungal Interactions in Chronic Lung Infections, G7436798587, Cancer Center Support Grant, Evolved Heterogeneity Contributes to Chronic Fungal Lung Infections
OpenAlex ID: W2899359448