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The incidence of drug tolerance, heteroresistance, and resistance is on the rise due to an overuse of antifungal drugs. The aim of this study was to expose a sensitive C. glabrata strain to sequentially increasing concentrations of two antifungal drugs, fluconazole, an azole that targets ergosterol biosynthesis, or caspofungin, an echinocandin that targets cell wall glucan synthesis. Analysis of the drug-exposed isolates showed development of antifungal tolerance, chromosomal abnormalities, decreased adhesion, attenuated virulence, and an increase in efflux pump activity. Furthermore, whole genome sequencing of all isolates exposed to different concentrations of fluconazole or caspofungin was performed to determine mutations in key genes that could correlate with the observed phenotypes. Mutations were found in genes implicated in adhesion, such as in the AWP, PWP, and EPA family of genes. Isolates exposed to higher drug concentrations displayed more mutations than those at lower concentrations.<\/jats:p>","DOI":"10.3390\/jof11040284","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T06:52:56Z","timestamp":1743749576000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Induction of Antifungal Tolerance Reveals Genetic and Phenotypic Changes in Candida glabrata"],"prefix":"10.3390","volume":"11","author":[{"given":"Christy","family":"Chedraoui","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Lebanese American University, Byblos P.O. 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Remodeling of the Candida Glabrata Cell Wall in the Gastrointestinal Tract Affects the Gut Microbiota and the Immune Response. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-21422-w"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1979877","DOI":"10.1080\/19490976.2021.1979877","article-title":"The Interplay between Gut Bacteria and the Yeast Candida Albicans","volume":"13","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1056\/NEJMra1315399","article-title":"Invasive Candidiasis","volume":"373","author":"Kullberg","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2147\/IDR.S80677","article-title":"Retrospective Analysis of Mortality and Candida Isolates of 75 Patients with Candidemia: A Single Hospital Experience","volume":"8","author":"Hirano","year":"2015","journal-title":"Infect. Drug Resist."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1086\/502581","article-title":"Excess Mortality, Hospital Stay, and Cost Due to Candidemia: A Case-Control Study Using Data from Population-Based Candidemia Surveillance","volume":"26","author":"Morgan","year":"2005","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00294-018-0867-z","article-title":"Genomes Shed Light on the Secret Life of Candida Glabrata: Not so Asexual, Not so Commensal","volume":"65","author":"Fairhead","year":"2019","journal-title":"Curr. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kumar, K., Askari, F., Sahu, M.S., and Kaur, R. (2019). Candida Glabrata: A Lot More Than Meets the Eye. Microorganisms, 7.","DOI":"10.3390\/microorganisms7020039"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s11046-008-9089-0","article-title":"Microsatellite DNA Identification and Genotyping of Candida Albicans from Lebanese Clinical Isolates","volume":"165","author":"Barada","year":"2008","journal-title":"Mycopathologia"},{"key":"ref_10","first-page":"755","article-title":"Molecular Typing of Candida Glabrata","volume":"185","author":"Bader","year":"2020","journal-title":"Mycopathologia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1574-6968.2000.tb09216.x","article-title":"Candida Glabrata Displays Pseudohyphal Growth","volume":"189","author":"Csank","year":"2000","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.18869\/acadpub.cmm.2.4.49","article-title":"Pseudohyphae Formation in Candida Glabrata Due to CO2 Exposure","volume":"2","author":"Sasani","year":"2016","journal-title":"Curr. Med. Mycol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s10096-005-0080-0","article-title":"Adverse Effects of Antifungal Therapies in Invasive Fungal Infections: Review and Meta-Analysis","volume":"25","author":"Girois","year":"2006","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ijantimicag.2017.05.019","article-title":"Epidemiology of Antifungal Resistance in Human Pathogenic Yeasts: Current Viewpoint and Practical Recommendations for Management","volume":"50","author":"Farmakiotis","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bhattacharya, S., Sae-Tia, S., and Fries, B.C. (2020). Candidiasis and Mechanisms of Antifungal Resistance. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060312"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, F., and Berman, J. (2024). Beyond Resistance: Antifungal Heteroresistance and Antifungal Tolerance in Fungal Pathogens. Curr. Opin. Microbiol., 78.","DOI":"10.1016\/j.mib.2024.102439"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Suchodolski, J., Muraszko, J., Bernat, P., and Krasowska, A. (2019). A Crucial Role for Ergosterol in Plasma Membrane Composition, Localisation, and Activity of Cdr1p and H+-ATPase in Candida Albicans. Microorganisms, 7.","DOI":"10.3390\/microorganisms7100378"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1473-3099(02)00181-0","article-title":"Resistance of Candida Species to Antifungal Agents: Molecular Mechanisms and Clinical Consequences","volume":"2","author":"Sanglard","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/QCO.0000000000000111","article-title":"Echinocandin Resistance: An Emerging Clinical Problem?","volume":"27","author":"Arendrup","year":"2014","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/molbev\/msz104","article-title":"Aneuploidy Enables Cross-Adaptation to Unrelated Drugs","volume":"36","author":"Yang","year":"2019","journal-title":"Mol. Biol. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41579-019-0322-2","article-title":"Drug Resistance and Tolerance in Fungi","volume":"18","author":"Berman","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Schwarzm\u00fcller, T., Ma, B., Hiller, E., Istel, F., Tscherner, M., Brunke, S., Ames, L., Firon, A., Green, B., and Cabral, V. (2014). Systematic Phenotyping of a Large-Scale Candida Glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004211"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103953","DOI":"10.1016\/j.isci.2022.103953","article-title":"The Role of Candida Albicans Stress Response Pathways in Antifungal Tolerance and Resistance","volume":"25","author":"Iyer","year":"2022","journal-title":"iScience"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Prasad, R., and Rawal, M.K. (2014). Efflux Pump Proteins in Antifungal Resistance. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00202"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.mib.2013.03.007","article-title":"Candida Albicans Biofilms: Building a Heterogeneous, Drug-Tolerant Environment","volume":"16","author":"Bonhomme","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a019752","DOI":"10.1101\/cshperspect.a019752","article-title":"Mechanisms of Antifungal Drug Resistance","volume":"5","author":"Cowen","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Prasad, R., Nair, R., and Banerjee, A. (2019). Multidrug Transporters of Candida Species in Clinical Azole Resistance. Fungal Genet. Biol., 132.","DOI":"10.1016\/j.fgb.2019.103252"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bcp.2016.11.019","article-title":"Antifungals","volume":"133","author":"Campoy","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/myc.12330","article-title":"Antifungal Drug Resistance among Candida Species: Mechanisms and Clinical Impact","volume":"58","author":"Sanguinetti","year":"2015","journal-title":"Mycoses"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1567-1364.2011.00728.x","article-title":"Differential Cell Wall Remodeling of Two Chitin Synthase Deletants \u0394chs3A and \u0394chs3B in the Pathogenic Yeast Candida Glabrata","volume":"11","author":"Ueno","year":"2011","journal-title":"FEMS Yeast Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/cmi.12364","article-title":"An Essential Role for Phosphatidylinositol 3-Kinase in the Inhibition of Phagosomal Maturation, Intracellular Survival and Virulence in Candida Glabrata","volume":"17","author":"Rai","year":"2015","journal-title":"Cell Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Timmermans, B., De Las Pe\u00f1as, A., Casta\u00f1o, I., and Van Dijck, P. (2018). Adhesins in Candida Glabrata. J. Fungi, 4.","DOI":"10.3390\/jof4020060"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"fov111","DOI":"10.1093\/femsyr\/fov111","article-title":"Biofilm Formation in Candida Glabrata: What Have We Learnt from Functional Genomics Approaches?","volume":"16","author":"Janbon","year":"2016","journal-title":"FEMS Yeast Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00277-19","DOI":"10.1128\/mSphere.00277-19","article-title":"Atomic Force Microscopy Demonstrates That Candida Glabrata Uses Three Epa Proteins to Mediate Adhesion to Abiotic Surfaces","volume":"4","author":"Valotteau","year":"2019","journal-title":"mSphere"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"El Hachem, S., Fattouh, N., Chedraoui, C., Finianos, M., Bitar, I., and Khalaf, R.A. (2024). Sequential Induction of Drug Resistance and Characterization of an Initial Candida Albicans Drug-Sensitive Isolate. J. Fungi, 10.","DOI":"10.3390\/jof10050347"},{"key":"ref_36","unstructured":"Alexander, B.D., Procop, G.W., Dufresne, P., and Clinical and Laboratory Standards Institute (2017). Performance Standards for Antifungal Susceptibility Testing of Yeasts, CLSI."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), Rodr\u00edguez-Tudela, J.L., Barchiesi, F., Bille, J., Chryssanthou, E., Cuenca-Estrella, M., Denning, D., Donnelly, J.P., Dupont, B., and Fegeler, W. (2003). Method for the Determination of Minimum Inhibitory Concentration (MIC) by Broth Dilution of Fermentative Yeasts. Clin. Microbiol. Infect., 9, i\u2013viii.","DOI":"10.1046\/j.1469-0691.2003.00789.x"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e13750","DOI":"10.1111\/myc.13750","article-title":"Adhesive and Biofilm-Forming Candida Glabrata Lebanese Hospital Isolates Harbour Mutations in Subtelomeric Silencers and Adhesins","volume":"67","author":"Fattouh","year":"2024","journal-title":"Mycoses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jgar.2024.02.012","article-title":"Candida Glabrata Hospital Isolate from Lebanon Reveals Micafungin Resistance Associated with Increased Chitin and Resistance to a Cell-Surface-Disrupting Agent","volume":"37","author":"Fattouh","year":"2024","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_40","first-page":"100","article-title":"YMAP: A Pipeline for Visualization of Copy Number Variation and Loss of Heterozygosity in Eukaryotic Pathogens","volume":"6","author":"Abbey","year":"2014","journal-title":"Genome Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.fgb.2019.02.008","article-title":"Genotypic and Phenotypic Characterization of Candida Albicans Lebanese Hospital Isolates Resistant and Sensitive to Caspofungin","volume":"127","author":"Toutounji","year":"2019","journal-title":"Fungal Genet. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/jac\/44.1.27","article-title":"Rhodamine 6G Efflux for the Detection of CDR1-Overexpressing Azole-Resistant Candidaalbicans Strains","volume":"44","author":"Maesaki","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fattouh, N., Hdayed, D., Geukgeuzian, G., Tokajian, S., and Khalaf, R.A. (2021). Molecular Mechanism of Fluconazole Resistance and Pathogenicity Attributes of Lebanese Candida Albicans Hospital Isolates. Fungal Genet. Biol., 153.","DOI":"10.1016\/j.fgb.2021.103575"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.micres.2010.08.004","article-title":"The Candida Albicans Hwp2 Is Necessary for Proper Adhesion, Biofilm Formation and Oxidative Stress Tolerance","volume":"166","author":"Younes","year":"2011","journal-title":"Microbiol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1128\/JCM.37.10.3332-3337.1999","article-title":"Quantitation of Ergosterol Content: Novel Method for Determination of Fluconazole Susceptibility of Candida Albicans","volume":"37","author":"Jradi","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"El Khoury, P., Awad, A., Wex, B., and Khalaf, R.A. (2018). Proteomic Analysis of a Candida Albicans Pir32 Null Strain Reveals Proteins Involved in Adhesion, Filamentation and Virulence. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194403"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1046\/j.1365-2958.2000.01729.x","article-title":"The Cell Wall Architecture of Candida Albicans Wild-Type Cells and Cell Wall-Defective Mutants","volume":"35","author":"Kapteyn","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/13693780802549594","article-title":"Biofilms of Non-Candida Albicans Candida Species: Quantification, Structure and Matrix Composition","volume":"47","author":"Silva","year":"2009","journal-title":"Med. Mycol."},{"key":"ref_49","first-page":"fov025","article-title":"Tipping the Balance Both Ways: Drug Resistance and Virulence in Candida Glabrata","volume":"15","author":"Sanglard","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Al-Baqsami, Z.F., Ahmad, S., and Khan, Z. (2020). Antifungal Drug Susceptibility, Molecular Basis of Resistance to Echinocandins and Molecular Epidemiology of Fluconazole Resistance among Clinical Candida Glabrata Isolates in Kuwait. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63240-z"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1128\/AAC.49.2.668-679.2005","article-title":"Mechanisms of Azole Resistance in Clinical Isolates of Candida Glabrata Collected during a Hospital Survey of Antifungal Resistance","volume":"49","author":"Sanguinetti","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"R1520","DOI":"10.1016\/j.cub.2021.09.071","article-title":"Antifungal Drug Resistance: Deciphering the Mechanisms Governing Multidrug Resistance in the Fungal Pathogen Candida Glabrata","volume":"31","author":"Robbins","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Healey, K.R., and Perlin, D.S. (2018). Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida Glabrata. J. Fungi, 4.","DOI":"10.20944\/preprints201808.0306.v1"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Walker, L.A., Munro, C.A., de Bruijn, I., Lenardon, M.D., McKinnon, A., and Gow, N.A.R. (2008). Stimulation of Chitin Synthesis Rescues Candida Albicans from Echinocandins. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000040"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Reithofer, V., Fern\u00e1ndez-Pereira, J., Alvarado, M., de Groot, P., and Essen, L.-O. (2021). A Novel Class of Candida Glabrata Cell Wall Proteins with \u03b2-Helix Fold Mediates Adhesion in Clinical Isolates. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009980"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"fov098","DOI":"10.1093\/femsyr\/fov098","article-title":"Proteomic Analysis of Hyperadhesive Candida Glabrata Clinical Isolates Reveals a Core Wall Proteome and Differential Incorporation of Adhesins","volume":"15","author":"Dekker","year":"2015","journal-title":"FEM Yeast Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s10096-013-2009-3","article-title":"Candida Glabrata: A Review of Its Features and Resistance","volume":"33","author":"Rodrigues","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16864","DOI":"10.1073\/pnas.1207653109","article-title":"Structural Basis for Promiscuity and Specificity during Candida Glabrata Invasion of Host Epithelia","volume":"109","author":"Diderrich","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1016\/S2666-5247(23)00067-8","article-title":"Worldwide Emergence of Fluconazole-Resistant Candida Parapsilosis: Current Framework and Future Research Roadmap","volume":"4","author":"Daneshnia","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ferrari, S., Ischer, F., Calabrese, D., Posteraro, B., Sanguinetti, M., Fadda, G., Rohde, B., Bauser, C., Bader, O., and Sanglard, D. (2009). Gain of Function Mutations in CgPDR1 of Candida Glabrata Not Only Mediate Antifungal Resistance but Also Enhance Virulence. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000268"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"foac019","DOI":"10.1093\/femsyr\/foac019","article-title":"The Effect of Antifungal Resistance Development on the Virulence of Candida Species","volume":"22","author":"Bohner","year":"2022","journal-title":"FEMS Yeast Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/cid\/cit136","article-title":"Increasing Echinocandin Resistance in Candida Glabrata: Clinical Failure Correlates with Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations","volume":"56","author":"Alexander","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"iyac031","DOI":"10.1093\/genetics\/iyac031","article-title":"Population Genetics and Microevolution of Clinical Candida Glabrata Reveals Recombinant Sequence Types and Hyper-Variation within Mitochondrial Genomes, Virulence Genes, and Drug Targets","volume":"221","author":"Helmstetter","year":"2022","journal-title":"Genetics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/AAC.03470-14","article-title":"Contribution of Clinically Derived Mutations in ERG11 to Azole Resistance in Candida Albicans","volume":"59","author":"Flowers","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/AAC.01486-12","article-title":"Elevated Chitin Content Reduces the Susceptibility of Candida Species to Caspofungin","volume":"57","author":"Walker","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1128\/EC.00073-10","article-title":"Genomewide Expression Profile Analysis of the Candida Glabrata Pdr1 Regulon","volume":"10","author":"Caudle","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e01692-18","DOI":"10.1128\/AAC.01692-18","article-title":"Spontaneous Mutational Frequency and FKS Mutation Rates Vary by Echinocandin Agent against Candida Glabrata","volume":"63","author":"Shields","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e00995-18","DOI":"10.1128\/AAC.00995-18","article-title":"A Transcriptomics Approach To Unveiling the Mechanisms of In Vitro Evolution towards Fluconazole Resistance of a Candida Glabrata Clinical Isolate","volume":"63","author":"Cavalheiro","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1016\/j.cub.2021.09.084","article-title":"Narrow Mutational Signatures Drive Acquisition of Multidrug Resistance in the Fungal Pathogen Candida Glabrata","volume":"31","author":"Ksiezopolska","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the Emerging Threat of Antifungal Resistance to Human Health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. 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