{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:16:09Z","timestamp":1791807369794,"version":"4.3.4"},"reference-count":151,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2015-67107"],"award-info":[{"award-number":["BFU2015-67107"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["H2020-MSCA-ITN-2014-642095"],"award-info":[{"award-number":["H2020-MSCA-ITN-2014-642095"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.<\/jats:p>","DOI":"10.3390\/genes9090461","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T10:50:31Z","timestamp":1537354231000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":217,"title":["Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens"],"prefix":"10.3390","volume":"9","author":[{"given":"Ewa","family":"Ksiezopolska","sequence":"first","affiliation":[{"name":"Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain"},{"name":"Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Gabald\u00f3n","sequence":"additional","affiliation":[{"name":"Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain"},{"name":"Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), 08010 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"ref_1","unstructured":"(2017). Stop neglecting fungi. Nat. Microbiol., 2, 17120."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: Human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ii13","DOI":"10.1093\/jac\/dkw392","article-title":"The current treatment landscape: Candidiasis","volume":"71","author":"Bassetti","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"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":"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_6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.diagmicrobio.2016.02.009","article-title":"Antifungal susceptibility patterns of a global collection of fungal isolates: Results of the SENTRY Antifungal Surveillance Program (2013)","volume":"85","author":"Castanheira","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1093\/cid\/cis200","article-title":"Performance of Candida real-time polymerase chain reaction, \u03b2-d-glucan assay, and blood cultures in the diagnosis of invasive candidiasis","volume":"54","author":"Nguyen","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1093\/jac\/dku225","article-title":"Clinical validation of a multiplex real-time PCR assay for detection of invasive candidiasis in intensive care unit patients","volume":"69","author":"Meije","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"fow064","DOI":"10.1093\/femsyr\/fow064","article-title":"Evolutionary genomics of yeast pathogens in the Saccharomycotina","volume":"16","year":"2016","journal-title":"FEMS Yeast Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S0966-842X(03)00117-3","article-title":"Antifungal agents: Mechanisms of action","volume":"11","author":"Odds","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0891-5520(20)30683-8","article-title":"Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management","volume":"9","author":"Fraimow","year":"1995","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1099\/jmm.0.045054-0","article-title":"Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options","volume":"62","author":"Sardi","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rodrigues, C., Rodrigues, M., Silva, S., and Henriques, M. (2017). Candida glabrata biofilms: How far have we come?. J. Fungi, 3.","DOI":"10.3390\/jof3010011"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pfaller, M.A., Andes, D.R., Diekema, D.J., Horn, D.L., Reboli, A.C., Rotstein, C., Franks, B., and Azie, N.E. (2014). Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2496 patients: Data from the Prospective Antifungal Therapy (PATH) registry 2004\u20132008. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101510"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1128\/JCM.00308-13","article-title":"Echinocandin and triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates collected from 2010 to 2011: Application of new CLSI clinical breakpoints and epidemiological cutoff values for characterization of geographic","volume":"51","author":"Pfaller","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/cid\/ciw691","article-title":"Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses","volume":"64","author":"Lockhart","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.amjmed.2011.11.001","article-title":"Antifungal drug resistance: Mechanisms, epidemiology, and consequences for treatment","volume":"125","author":"Pfaller","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_18","first-page":"18","article-title":"On the role of genomic islands in bacterial pathogenicity and antimicrobial resistance","volume":"2","author":"Mohammad","year":"2014","journal-title":"Cloud Publ. Int. J. Adv. Biotechnol. Bioeng."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Weete, J.D., Abril, M., and Blackwell, M. (2010). Phylogenetic distribution of fungal sterols. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010899"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1128\/CMR.12.1.40","article-title":"Current and emerging azole antifungal agents","volume":"12","author":"Sheehan","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0924-8579(00)00258-2","article-title":"Current and future antifungal therapy: New targets for antifungal therapy","volume":"16","author":"Andriole","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1345\/aph.1M237","article-title":"Echinocandins: The newest class of antifungals","volume":"43","author":"Sucher","year":"2009","journal-title":"Ann. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1016\/j.bmc.2012.04.045","article-title":"The biology and chemistry of antifungal agents: A review","volume":"20","author":"Kathiravan","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrd.2017.46","article-title":"The antifungal pipeline: A reality check","volume":"16","author":"Perfect","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S1054-3589(08)60129-5","article-title":"Clinical pharmacology of systemic antifungal agents: A comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development","volume":"44","author":"Groll","year":"1998","journal-title":"Adv. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/978-1-59745-180-2_27","article-title":"Flucytosine: Site of Action, Mechanism of Resistance and Use in Combination Therapy","volume":"Volume 48","author":"Chandra","year":"2009","journal-title":"Antimicrobial Drug Resistance"},{"key":"ref_28","unstructured":"World Health Organization (2015). WHO Model List of Essential Medicines\u201419th List (April 2015). Essent. Med., 1\u201345."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1128\/AAC.02265-15","article-title":"Acquired flucytosine resistance during combination therapy with caspofungin and flucytosine for Candida glabrata cystitis","volume":"60","author":"Charlier","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.riam.2013.10.001","article-title":"Epidemiology of candidaemia and invasive candidiasis. A changing face","volume":"31","year":"2014","journal-title":"Rev. Iberoam. Micol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pappas, P.G., Lionakis, M.S., Arendrup, M.C., Ostrosky-Zeichner, L., and Kullberg, B.J. (2018). Invasive candidiasis. Nat. Rev. Dis. Prim., 4.","DOI":"10.1038\/nrdp.2018.26"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1574-6976.2011.00278.x","article-title":"Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance","volume":"36","author":"Silva","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_33","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_34","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_35","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1128\/AAC.00262-08","article-title":"A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility","volume":"52","author":"Katiyar","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"204237","DOI":"10.1155\/2013\/204237","article-title":"Candida infections, causes, targets, and resistance mechanisms: Traditional and alternative antifungal agents","volume":"2013","author":"Spampinato","year":"2013","journal-title":"Biomed Res. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1086\/313749","article-title":"Practice guidelines for the treatment of candidiasis","volume":"30","author":"Rex","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/ajt.14121","article-title":"Investigation of the first Seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus-United States, May 2013\u2013August 2016","volume":"17","author":"Vallabhaneni","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jhin.2016.08.004","article-title":"Multidrug-resistant Candida auris: \u2018New kid on the block\u2019 in hospital-associated infections?","volume":"94","author":"Chowdhary","year":"2016","journal-title":"J. Hosp. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1093\/cid\/cis697","article-title":"Changes in incidence and antifungal drug resistance in candidemia: Results from population-based laboratory surveillance in Atlanta and Baltimore, 2008\u20132011","volume":"55","author":"Cleveland","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.diagmicrobio.2015.04.008","article-title":"Isavuconazole, micafungin, and 8 comparator antifungal agents\u2019 susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: Temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and prop","volume":"82","author":"Pfaller","year":"2015","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/1469-0691.12513","article-title":"Update on antifungal resistance in Aspergillus and Candida","volume":"20","author":"Arendrup","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1128\/JCM.02117-09","article-title":"Results from the artemis disk global antifungal surveillance study, 1997 to 2007: A 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion","volume":"48","author":"Pfaller","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1128\/AAC.01128-10","article-title":"Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: A prospective multicenter study involving 2441 patients","volume":"55","author":"Lortholary","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3201\/eid2011.140685","article-title":"Drug-Resistant Candida glabrata infection in cancer patients","volume":"20","author":"Farmakiotis","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Vallabhaneni, S., Cleveland, A.A., Farley, M.M., Harrison, L.H., Schaffner, W., Beldavs, Z.G., Derado, G., Pham, C.D., Lockhart, S.R., and Smith, R.M. (2015). Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: Data from a large multisite population-based candidemia surveillance program, 2008\u20132014. Open Forum Infect. Dis., 2.","DOI":"10.1093\/ofid\/ofv163"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1128\/JCM.06112-11","article-title":"Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata","volume":"50","author":"Pfaller","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1128\/AAC.03255-14","article-title":"Role of FKS mutations in Candida glabrata: MIC values, echinocandin resistance, and multidrug resistance","volume":"58","author":"Pham","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1086\/500939","article-title":"Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient","volume":"42","author":"Arendrup","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1128\/AAC.00348-10","article-title":"Identification and characterization of four azole-resistant ERG3 mutants of Candida albicans","volume":"54","author":"Martel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1128\/AAC.00555-13","article-title":"Molecular mechanisms of drug resistance in clinical Candida species isolated from Tunisian hospitals","volume":"57","author":"Eddouzi","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1128\/AAC.00477-13","article-title":"Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications","volume":"57","author":"Forastiero","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1128\/JCM.01998-13","article-title":"Epidemiology, species distribution, antifungal susceptibility, and outcome of Candidemia across five sites in Italy and Spain","volume":"51","author":"Bassetti","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s15010-013-0455-6","article-title":"A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade","volume":"41","author":"Tortorano","year":"2013","journal-title":"Infection"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.mimet.2010.05.002","article-title":"Correlation between broth microdilution and disk diffusion methods for antifungal susceptibility testing of caspofungin, voriconazole, amphotericin B, itraconazole and fluconazole against Candida glabrata","volume":"82","author":"Kiraz","year":"2010","journal-title":"J. Microbiol. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1128\/AAC.02037-12","article-title":"Rapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin","volume":"57","author":"Fekkar","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.1128\/AAC.02204-15","article-title":"Acquired multidrug antifungal resistance in Candida lusitaniae during therapy","volume":"59","author":"Asner","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/jac\/dks186","article-title":"Amino acid substitutions in the Candida albicans sterol \u03b45,6-desaturase (Erg3p) confer azole resistance: Characterization of two novel mutants with impaired virulence","volume":"67","author":"Morio","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1128\/AAC.00303-10","article-title":"A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14\u03b1-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B","volume":"54","author":"Martel","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1093\/jac\/dkv140","article-title":"Stepwise emergence of azole, echinocandin and amphotericin B multidrug resistance in vivo in Candida albicans orchestrated by multiple genetic alterations","volume":"70","author":"Jensen","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/bfgp\/elv035","article-title":"Budding off: Bringing functional genomics to Candida albicans","volume":"15","author":"Anderson","year":"2016","journal-title":"Brief. Funct. Genom."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cub.2017.11.027","article-title":"Patterns of genomic variation in the opportunistic pathogen Candida glabrata suggest the existence of mating and a secondary association with humans","volume":"28","author":"Ksiezopolska","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1128\/EC.00060-10","article-title":"Genomic plasticity of the human fungal pathogen Candida albicans","volume":"9","author":"Selmecki","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1128\/AAC.44.10.2693-2700.2000","article-title":"Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors","volume":"44","author":"Henry","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ben-Ami, R. (2018). Treatment of invasive candidiasis: A narrative review. J. Fungi, 4.","DOI":"10.3390\/jof4030097"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1128\/CMR.11.2.382","article-title":"Clinical, cellular, and molecular factors that contribute to antifungal drug resistance","volume":"11","author":"White","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ijantimicag.2017.05.012","article-title":"Molecular basis of antifungal drug resistance in yeasts","volume":"50","author":"Morio","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1128\/MMBR.00045-10","article-title":"Regulatory circuitry governing fungal development, drug resistance, and disease","volume":"75","author":"Shapiro","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S1471-4914(02)02280-3","article-title":"Molecular basis of resistance to azole antifungals","volume":"8","author":"Lupetti","year":"2002","journal-title":"Trends Mol. Med."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/1567-1364.12042","article-title":"Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans","volume":"13","author":"Xiang","year":"2013","journal-title":"FEMS Yeast Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S118892","article-title":"Fluconazole resistance in Candida species: A current perspective","volume":"10","author":"Berkow","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"a019752","DOI":"10.1101\/cshperspect.a019752","article-title":"Mechanisms of Antifungal Drug Resistance","volume":"5","author":"Cowen","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1128\/AAC.49.5.1745-1752.2005","article-title":"Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes","volume":"49","author":"MacPherson","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","first-page":"1603","article-title":"The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans","volume":"3","author":"Barker","year":"2007","journal-title":"PLoS Pathog."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1128\/EC.3.6.1639-1652.2004","article-title":"TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2","volume":"3","author":"Coste","year":"2004","journal-title":"Eukaryot. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1128\/AAC.00926-08","article-title":"Relative contributions of the Candida albicans ABC transporters Cdr1p and Cdr2p to clinical azole resistance","volume":"53","author":"Tsao","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1128\/EC.00069-09","article-title":"Functional analysis of cis-and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system","volume":"8","author":"Coste","year":"2009","journal-title":"Eukaryot. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1093\/jac\/dkq354","article-title":"Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients","volume":"65","author":"Siikala","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1534\/genetics.105.054767","article-title":"A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans","volume":"172","author":"Coste","year":"2006","journal-title":"Genetics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1126\/science.1128242","article-title":"Aneuploidy and isochromosome formation in drug-resistant Candida albicans","volume":"313","author":"Selmecki","year":"2006","journal-title":"Science"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1534\/genetics.117.300295","article-title":"Parasex generates phenotypic diversity de novo and impacts drug resistance and virulence in Candida albicans","volume":"207","author":"Hirakawa","year":"2017","journal-title":"Genetics"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Zhang, L., Xiao, M., Watts, M.R., Wang, H., Fan, X., Kong, F., and Xu, Y.C. (2015). Development of fluconazole resistance in a series of Candida parapsilosis isolates from a persistent candidemia patient with prolonged antifungal therapy. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1086-6"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1128\/AAC.01177-15","article-title":"Candida parapsilosis resistance to fluconazole: Molecular mechanisms and in vivo impact in infected Galleria mellonella larvae","volume":"59","author":"Souza","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1128\/AAC.01358-15","article-title":"Multidrug transporters and alterations in sterol biosynthesis contribute to azole antifungal resistance in Candida parapsilosis","volume":"59","author":"Berkow","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1128\/AAC.04613-14","article-title":"Molecular mechanisms of fluconazole resistance in Candida parapsilosis isolates from a U.S. surveillance system","volume":"59","author":"Grossman","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1128\/AAC.01127-10","article-title":"Transcriptional profiling of azole-resistant Candida parapsilosis strains","volume":"55","author":"Silva","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11046-014-9831-8","article-title":"The A395T Mutation in ERG11 gene confers fluconazole resistance in Candida tropicalis causing candidemia","volume":"179","author":"Tan","year":"2015","journal-title":"Mycopathologia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/jac\/dks481","article-title":"Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China","volume":"68","author":"Jiang","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1128\/AAC.44.6.1578-1584.2000","article-title":"Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750","volume":"44","author":"Barchiesi","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1128\/AAC.42.10.2645","article-title":"Mechanism of fluconazole resistance in Candida krusei","volume":"42","author":"Orozco","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","first-page":"276","article-title":"Upregulation of the ERG11 gene in Candida krusei by azoles","volume":"18","author":"Tavakoli","year":"2010","journal-title":"Daru"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1128\/AAC.01095-08","article-title":"Abc1p is a multidrug efflux transporter that tips the balance in favor of innate azole resistance in Candida krusei","volume":"53","author":"Lamping","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1590\/0074-02760150400","article-title":"Novel point mutations in the ERG11 gene in clinical isolates of azole resistant Candida species","volume":"111","author":"Grisolia","year":"2016","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1128\/AAC.43.11.2753","article-title":"The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents","volume":"43","author":"Sanglard","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1128\/AAC.48.10.3773-3781.2004","article-title":"Azole resistance in Candida glabrata: Coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor","volume":"48","author":"Vermitsky","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","first-page":"1","article-title":"Drug resistance mechanisms and their regulation in non-albicans Candida species","volume":"71","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/jac\/dkn381","article-title":"Fungaemia caused by Candida glabrata with reduced susceptibility to fluconazole due to altered gene expression: Risk factors, antifungal treatment and outcome","volume":"62","author":"Tumbarello","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3389\/fmicb.2016.00526","article-title":"Clotrimazole Drug Resistance in Candida glabrata Clinical Isolates Correlates with Increased Expression of the Drug: H+ Antiporters CgAqr1, CgTpo1_1, CgTpo3, and CgQdr2","volume":"7","author":"Costa","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1128\/AAC.01271-10","article-title":"Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice","volume":"55","author":"Ferrari","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1128\/AAC.48.5.1600-1613.2004","article-title":"Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: Roles of calcium signaling and mitochondria","volume":"48","author":"Kaur","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1128\/AAC.01364-09","article-title":"Roles of calcineurin and Crz1 in antifungal susceptibility and virulence of Candida glabrata","volume":"54","author":"Miyazaki","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Salazar, S.B., Wang, C., Musterkotter, M., Okamoto, M., Takahashi-Nakaguchi, A., Chibana, H., Lopes, M.M., G\u00fcldener, U., Butler, G., and Mira, N.P. (2017). Comparative genomic and transcriptomic analyses unveil novel features of azole resistance and adaptation to the human host in Candida glabrata. FEMS Yeast Res.","DOI":"10.1093\/femsyr\/fox079"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1128\/AAC.01653-05","article-title":"Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1","volume":"50","author":"Balashov","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1128\/AAC.01711-09","article-title":"Low prevalence of FKS1 hot spot 1 mutations in a worldwide collection of Candida strains","volume":"54","author":"Castanheira","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1128\/AAC.00443-09","article-title":"Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-\u03b2-D-glucan synthase: Implication for the existing susceptibility breakpoint","volume":"53","author":"Lee","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ijantimicag.2014.06.007","article-title":"Activity of echinocandins and triazoles against a contemporary (2012) worldwide collection of yeast and molds collected from invasive infections","volume":"44","author":"Castanheira","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1128\/AAC.00813-12","article-title":"Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: Implications for echinocandin resistance","volume":"56","author":"Katiyar","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.fgb.2009.09.003","article-title":"Fungal echinocandin resistance","volume":"47","author":"Walker","year":"2010","journal-title":"Fungal Genet. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Huang, W., Liao, G., Baker, G.M., Wang, Y., Lau, R., Paderu, P., Perlin, D.S., and Xue, C. (2016). Lipid flippase subunit Cdc50 mediates drug resistance and virulence in Cryptococcus neoformans. MBio, 7.","DOI":"10.1128\/mBio.00478-16"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1128\/AAC.01145-12","article-title":"Two clinical isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B both harbor mutations in ERG2","volume":"56","author":"Hull","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1128\/AAC.00423-08","article-title":"A nonsense mutation in the ERG6 gene leads to reduced susceptibility to polyenes in a clinical isolate of Candida glabrata","volume":"52","author":"Vandeputte","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1128\/AAC.48.11.4377-4386.2004","article-title":"Molecular mechanisms of primary resistance to flucytosine in Candida albicans","volume":"48","author":"Hope","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1128\/AAC.49.8.3101-3108.2005","article-title":"Inactivation of the FCY2 gene encoding purine-cytosine permease promotes cross-resistance to flucytosine and fluconazole in Candida lusitaniae","volume":"49","author":"Bouchoux","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11046-010-9342-1","article-title":"Molecular Mechanisms of Resistance to 5-Fluorocytosine in Laboratory Mutants of Candida glabrata","volume":"171","author":"Vandeputte","year":"2011","journal-title":"Mycopathologia"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Costa, C., Ponte, A., Pais, P., Santos, R., Cavalheiro, M., Yaguchi, T., Chibana, H., and Teixeira, M.C. (2015). New mechanisms of flucytosine resistance in C. glabrata unveiled by a chemogenomics analysis in S. cerevisiae. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135110"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1128\/EC.00215-12","article-title":"Gain-of-function mutations in UPC2 are a frequent cause of ERG11 upregulation in azole-resistant clinical isolates of Candida albicans","volume":"11","author":"Flowers","year":"2012","journal-title":"Eukaryot. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1365-2958.2012.08210.x","article-title":"The stepwise acquisition of fluconazole resistance mutations causes a gradual loss of fitness in Candida albicans","volume":"86","author":"Sasse","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.1128\/AAC.01519-13","article-title":"Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: Should the clinical laboratory be testing this agent?","volume":"57","author":"Arendrup","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1128\/AAC.00095-07","article-title":"Paradoxical effect of echinocandins across Candida species in vitro: Evidence for echinocandin-specific and Candida species-related differences","volume":"51","author":"Chamilos","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4862","DOI":"10.1128\/AAC.00027-12","article-title":"The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata","volume":"56","author":"Shields","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1128\/AAC.01053-05","article-title":"Impact of antimicrobial dosing regimen on evolution of drug resistance in vivo: Fluconazole and Candida albicans","volume":"50","author":"Andes","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"11283","DOI":"10.1073\/pnas.201398998","article-title":"Origin of multidrug resistance in cells with and without multidrug resistance genes: Chromosome reassortments catalyzed by aneuploidy","volume":"98","author":"Duesberg","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Selmecki, A.M., Dulmage, K., Cowen, L.E., Anderson, J.B., and Berman, J. (2009). Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000705"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sionov, E., Lee, H., Chang, Y.C., and Kwon-Chung, K.J. (2010). Cryptococcus neoformans Overcomes Stress of Azole Drugs by Formation of Disomy in Specific Multiple Chromosomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000848"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/j.1365-2958.2008.06176.x","article-title":"An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1","volume":"68","author":"Selmecki","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Healey, K.R., Ortigosa, C.J., Shor, E., and Perlin, D.S. (2016). Genetic drivers of multidrug resistance in Candida glabrata. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01995"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1128\/AAC.41.10.2229","article-title":"Molecular biological characterization of an azole-resistant Candida glabrata isolate","volume":"41","author":"Marichal","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/1567-1364.12145","article-title":"Genome structure and dynamics of the yeast pathogen Candida glabrata","volume":"14","author":"Ahmad","year":"2014","journal-title":"FEMS Yeast Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Bader, O., Schwarz, A., Kraneveld, E.A., Tangwattanchuleeporn, M., Schmidt, P., Jacobsen, M.D., Gross, U., de Groot, P.W.J., and Weig, M. (2012). Gross karyotypic and phenotypic alterations among Ddifferent progenies of the Candida glabrata CBS138\/ATCC2001 reference strain. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052218"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1128\/EC.00281-10","article-title":"Loss of heterozygosity at an unlinked genomic locus is responsible for the phenotype of a Candida albicans sap4\u0394 sap5\u0394 sap6\u0394 mutant","volume":"10","author":"Dunkel","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1469-0691.2006.01492.x","article-title":"The emergence of antibiotic resistance by mutation","volume":"13","author":"Woodford","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Boyce, K.J., Wang, Y., Verma, S., Shakya, V.P.S., Xue, C., and Idnurm, A. (2017). Mismatch repair of DNA replication errors contributes to microevolution in the pathogenic fungus Cryptococcus neoformans. MBio, 8.","DOI":"10.1128\/mBio.00595-17"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Healey, K.R., Zhao, Y., Perez, W.B., Lockhart, S.R., Sobel, J.D., Farmakiotis, D., Kontoyiannis, D.P., Sanglard, D., Taj-Aldeen, S.J., and Alexander, B.D. (2016). Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nat. Commun., 7.","DOI":"10.1038\/ncomms11128"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e00195-18","DOI":"10.1128\/AAC.00195-18","article-title":"Absence of azole or echinocandin resistance in Candida glabrata isolates in India despite background prevalence of strains with defects in DNA mismatch repair pathway","volume":"62","author":"Singh","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Ben-Ami, R., Zimmerman, O., Finn, T., Amit, S., Novikov, A., Wertheimer, N., Lurie-Weinberger, M., and Berman, J. (2016). Heteroresistance to fluconazole is a continuously distributed phenotype among Candida glabrata clinical strains associated with in vivo persistence. MBio, 7.","DOI":"10.1128\/mBio.00655-16"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nature13469","article-title":"Optimization of lag time underlies antibiotic tolerance in evolved bacterial populations","volume":"513","author":"Fridman","year":"2014","journal-title":"Nature"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.drup.2015.10.001","article-title":"Defining the frontiers between antifungal resistance, tolerance and the concept of persistence","volume":"23","author":"Delarze","year":"2015","journal-title":"Drug Resist. Updat."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Rosenberg, A., Ene, I.V., Bibi, M., Zakin, S., Segal, E.S., Ziv, N., Dahan, A.M., Colombo, A.L., Bennett, R.J., and Berman, J. (2018). Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-04926-x"},{"key":"ref_141","first-page":"1","article-title":"The evolution of drug resistance in clinical isolates of Candida albicans","volume":"2015","author":"Ford","year":"2015","journal-title":"Elife"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1128\/EC.05100-11","article-title":"Functional dissection of a Candida albicans zinc cluster transcription factor, the multidrug resistance regulator MRR1","volume":"10","author":"Schubert","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1534\/g3.117.042887","article-title":"Comparative Genomics of Two Sequential Candida glabrata Clinical Isolates","volume":"7","author":"Beaudoing","year":"2017","journal-title":"G3"},{"key":"ref_144","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_145","doi-asserted-by":"crossref","unstructured":"Singh-Babak, S.D., Babak, T., Diezmann, S., Hill, J.A., Xie, J.L., Chen, Y.L., Poutanen, S.M., Rennie, R.P., Heitman, J., and Cowen, L.E. (2012). Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002718"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"676.e7","DOI":"10.1016\/j.cmi.2017.03.014","article-title":"Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next-generation sequencing: A feasibility study","volume":"23","author":"Biswas","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.micro.56.012302.160907","article-title":"Evolution of drug resistance in Candida albicans","volume":"56","author":"Cowen","year":"2002","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/genetics\/163.4.1287","article-title":"Mode of selection and experimental evolution of antifungal drug resistance in Saccharomyces cerevisiae","volume":"163","author":"Anderson","year":"2003","journal-title":"Genetics"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.2217\/fmb.12.108","article-title":"Developing insights into the mechanisms of evolution of bacterial pathogens from whole-genome sequences","volume":"7","author":"Bryant","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1128\/JB.182.6.1515-1522.2000","article-title":"Evolution of drug resistance in experimental populations of Candida albicans","volume":"182","author":"Cowen","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1128\/EC.05168-11","article-title":"Evolutionary dynamics of Candida albicans during in vitro evolution","volume":"10","author":"Huang","year":"2011","journal-title":"Eukaryot. Cell"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/9\/461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:21:30Z","timestamp":1760196090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/9\/461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,19]]},"references-count":151,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["genes9090461"],"URL":"https:\/\/doi.org\/10.3390\/genes9090461","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,19]]}}}