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Among them, five strains of Candida parapsilosis complex were isolated during the early stage of hospitalization, while five strains of Candida tropicalis were isolated in the later stages of the disease. Using whole-genome sequencing, we distinguished the five strains of C. parapsilosis complex as four Candida metapsilosis strains and one Candida parapsilosis strain. Antifungal susceptibility testing showed that the five strains of C. parapsilosis complex were susceptible to all antifungal drugs, while five C. tropicalis strains had high minimum inhibitory concentrations to azoles, whereas antifungal-drug resistance gene analysis revealed the causes of azole resistance in such strains. For the first time, we analyzed the microevolutionary characteristics of pathogenic fungi in human hosts and inferred the infection time and parallel evolution of C. tropicalis strains. Molecular clock analysis revealed that azole-resistant C. tropicalis infection occurred during the first round of therapy, followed by divergence via parallel evolution in vivo. The presence\/absence variations indicated a potential decrease in the virulence of genomes in strains isolated following antifungal drug treatment, despite the absence of observed clinical improvement in the conditions of the patient. These results suggest that genomic analysis could serve as an auxiliary tool in guiding clinical diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/jof9080815","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:17:17Z","timestamp":1690975037000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vivo Microevolutionary Analysis of a Fatal Case of Rhinofacial and Disseminated Mycosis Due to Azole-Drug-Resistant Candida Species"],"prefix":"10.3390","volume":"9","author":[{"given":"Yuchen","family":"Wang","sequence":"first","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Guo","sequence":"additional","affiliation":[{"name":"TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjing 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8030-4490","authenticated-orcid":false,"given":"Xinran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Hu","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng","family":"Ma","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingchen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"},{"name":"School of Life Science & Technology, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongming","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Bioinformatics Center of AMMS, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Microbiology and Epidemiology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","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_2","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_3","doi-asserted-by":"crossref","unstructured":"Fu, J., Ding, Y., Jiang, Y., Mo, S., Xu, S., and Qin, P. (2018). Persistent candidemia in very low birth weight neonates: Risk factors and clinical significance. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3487-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1093\/infdis\/jiz573","article-title":"Distribution and antifungal susceptibility of Candida species causing candidemia in China: An update from the CHIF-NET study","volume":"221","author":"Xiao","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Da Matta, D.A., Souza, A.C.R., and Colombo, A.L. (2017). Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers. J. Fungi, 3.","DOI":"10.3390\/jof3020024"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.2174\/1568026619666191025152412","article-title":"New and promising chemotherapeutics for emerging infections involving drug-resistant non-albicans Candida species","volume":"19","author":"Silva","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11908-019-0702-9","article-title":"Antifungal resistance: A concerning trend for the present and future","volume":"21","author":"Hendrickson","year":"2019","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ksiezopolska, E., and Gabald\u00f3n, T. (2018). Evolutionary emergence of drug resistance in candida opportunistic pathogens. Genes, 9.","DOI":"10.3390\/genes9090461"},{"key":"ref_9","first-page":"766","article-title":"Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates","volume":"58","author":"Arastehfar","year":"2020","journal-title":"Mycology"},{"key":"ref_10","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. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S445","DOI":"10.1093\/infdis\/jix131","article-title":"Multidrug-resistant Candida: Epidemiology, molecular mechanisms, and treatment","volume":"216","author":"Arendrup","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4103\/jgid.jgid_74_19","article-title":"Persistence of Clonal Azole-Resistant Isolates of Candida albicans from a Patient with Chronic Mucocutaneous Candidiasis in Colombia","volume":"12","author":"Velez","year":"2020","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.mycmed.2018.02.004","article-title":"Chronic mucocutaneous candidiasis, a case study and literature review","volume":"28","author":"Khosravi","year":"2018","journal-title":"J. Mycol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e114","DOI":"10.1038\/cti.2016.71","article-title":"Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity","volume":"5","author":"Okada","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1111\/coa.13175","article-title":"A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?","volume":"43","author":"Vaughan","year":"2018","journal-title":"Clin. Otolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"595375","DOI":"10.3389\/fmicb.2020.595375","article-title":"Fatal Rhinofacial Mycosis Due to Aspergillus nomiae: Case Report and Review of Published Literature","volume":"11","author":"Zhou","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s12281-017-0276-7","article-title":"Harnessing Whole Genome Sequencing in Medical Mycology","volume":"11","author":"Cuomo","year":"2017","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1042\/BST20211123","article-title":"Using genomics to understand the mechanisms of virulence and drug resistance in fungal pathogens","volume":"50","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1007\/s10096-017-3024-6","article-title":"Bacterial genome sequencing in clinical microbiology: A pathogen-oriented review","volume":"36","author":"Tagini","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Salem-Bango, Z., Price, T.K., Chan, J.L., Chandrasekaran, S., Garner, O.B., and Yang, S. (2023). Fungal Whole-Genome Sequencing for Species Identification: From Test Development to Clinical Utilization. J. Fungi, 9.","DOI":"10.3390\/jof9020183"},{"key":"ref_21","unstructured":"Clinical and Laboratory Standards Institute (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [4th ed.]. Approved standard M27."},{"key":"ref_22","unstructured":"Clinical and Laboratory Standards Institute (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, Clinical and Laboratory Standards Institute. CLSI Document m38-A2."},{"key":"ref_23","unstructured":"Clinical and Laboratory Standards Institute (2018). Epidemiological Cutoff Values for Antifungal Susceptibility Testing, Clinical and Laboratory Standards Institute. [2nd ed.]. CLSI supplement M59."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13020-020-00365-3","article-title":"Genomic analyses reveal evolutionary and geologic context for the plateau fungus Ophiocordyceps sinensis","volume":"15","author":"Liu","year":"2020","journal-title":"Chin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3389\/fmicb.2016.01541","article-title":"Genome sequencing and comparative genomics analysis revealed pathogenic potential in Penicillium capsulatum as a novel fungal pathogen belonging to Eurotiales","volume":"7","author":"Yang","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9451","DOI":"10.1073\/pnas.1921046117","article-title":"RepeatModeler2 for automated genomic discovery of transposable element families","volume":"117","author":"Flynn","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","first-page":"4","article-title":"Using RepeatMasker to identify repetitive elements in genomic sequences","volume":"5","author":"Chen","year":"2009","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/bioinformatics\/btr010","article-title":"A novel hybrid gene prediction method employing protein multiple sequence alignments","volume":"27","author":"Keller","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jinf.2020.06.040","article-title":"Molecular identification of Cryptococcus gattii from cerebrospinal fluid using single-cell sequencing: A case study","volume":"81","author":"Chen","year":"2020","journal-title":"J. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis, version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13059-019-1832-y","article-title":"OrthoFinder: Phylogenetic orthology inference for comparative genomics","volume":"20","author":"Emms","year":"2019","journal-title":"Genome Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","article-title":"RAxML version 8: A tool for phylogenetic analysis and post-analysis of large phylogenies","volume":"30","author":"Stamatakis","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, T.H., Guo, H., Wang, X., Kim, C., and Paterson, A.H. (2014). SNPhylo: A pipeline to construct a phylogenetic tree from huge SNP data. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-162"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"vex042","DOI":"10.1093\/ve\/vex042","article-title":"TreeTime: Maximum-likelihood phylodynamic analysis","volume":"4","author":"Sagulenko","year":"2018","journal-title":"Virus Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41592-018-0001-7","article-title":"Accurate detection of complex structural variations using single-molecule sequencing","volume":"15","author":"Sedlazeck","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/978-1-0716-2293-3_19","article-title":"Variant annotation and functional prediction: SnpEff","volume":"2493","author":"Cingolani","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fcimb.2017.00105","article-title":"Genomics and comparative genomic analyses provide insight into the taxonomy and pathogenic potential of novel Emmonsia pathogens","volume":"7","author":"Yang","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.molp.2020.06.009","article-title":"TBtools: An integrative toolkit developed for interactive analyses of big Biological Data","volume":"13","author":"Chen","year":"2020","journal-title":"Mol. Plant"},{"key":"ref_44","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_45","doi-asserted-by":"crossref","unstructured":"Du, H., Zheng, Q., Bing, J., Bennett, R.J., and Huang, G. (2018). A coupled process of same- and opposite-sex mating generates polyploidy and genetic diversity in Candida tropicalis. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007377"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1093\/genetics\/61.4.893","article-title":"The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations","volume":"61","author":"Kimura","year":"1969","journal-title":"Genetics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1534\/g3.113.006429","article-title":"Lang and others, Mutation Rates, Spectra, and Genome-Wide Distribution of Spontaneous Mutations in Mismatch Repair Deficient Yeast","volume":"3","author":"Gregory","year":"2013","journal-title":"G3 Genes Genomes Genet."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pryszcz, L.P., N\u00e9meth, T., Saus, E., Ksiezopolska, E., Heged\u0171sov\u00e1, E., Nosek, J., Wolfe, K.H., Gacser, A., and Gabald\u00f3n, T. (2015). The Genomic Aftermath of Hybridization in the Opportunistic Pathogen Candida metapsilosis. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005626"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/j.1348-0421.2004.tb03623.x","article-title":"Characterization of mechanisms of fluconazole resistance in a Candida albicans isolate from a Japanese patient with chronic mucocutaneous candidiasis","volume":"48","author":"Kamai","year":"2004","journal-title":"Microbiol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1128\/AAC.49.11.4608-4615.2005","article-title":"Mechanisms of azole resistance in a clinical isolate of Candida tropicalis","volume":"49","author":"Vandeputte","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1128\/AAC.01102-09","article-title":"An A643T mutation in the transcription factor Upc2p causes constitutive ERG11 upregulation and increased fluconazole resistance in Candida albicans","volume":"54","author":"Heilmann","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1128\/AAC.00995-10","article-title":"An A643V amino acid substitution in Upc2p contributes to azole resistance in well-characterized clinical isolates of Candida albicans","volume":"55","author":"Hoot","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"6129","DOI":"10.1038\/ncomms7129","article-title":"Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2","volume":"6","author":"Yang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Morschh\u00e4user, J., Barker, K.S., Liu, T.T., BlaB-Warmuth, J., Homayouni, R., and Rogers, P.D. (2007). The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030164"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/j.1365-2958.2008.06309.x","article-title":"Mutations in the multi-drug resistance regulator MRR1, followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains","volume":"69","author":"Dunkel","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hampe, I.A.I., Friedman, J., Edgerton, M., and Morschh\u00e4user, J. (2017). An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006655"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/nature03448","article-title":"Sexual reproduction between partners of the same mating type in Cryptococcus neoformans","volume":"434","author":"Lin","year":"2005","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nature08252","article-title":"Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans","volume":"460","author":"Alby","year":"2009","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1016\/j.csbj.2022.06.030","article-title":"Population genomic analyses reveal evidence for limited recombination in the superbug Candida auris in nature","volume":"20","author":"Wang","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1136\/bmj.p709","article-title":"Drug resistant fungus is spreading in US long term care facilities and hospitals, warns CDC","volume":"380","author":"Tanne","year":"2023","journal-title":"BMJ"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"729476","DOI":"10.3389\/fcimb.2021.729476","article-title":"Molecular Epidemiology of Azole-Resistant Aspergillus fumigatus in France Shows Patient and Healthcare Links to Environmentally Occurring Genotypes","volume":"11","author":"Rocchi","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11684-017-0601-0","article-title":"Epidemiology of fungal infections in China","volume":"12","author":"Chen","year":"2018","journal-title":"Front. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"iyab028","DOI":"10.1093\/genetics\/iyab028","article-title":"Factors that influence bidirectional long-tract homozygosis due to double-strand break repair in Candida albicans","volume":"218","author":"Marton","year":"2021","journal-title":"Genetics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41467-019-13890-z","article-title":"5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus","volume":"11","author":"Billmyre","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e03348-20","DOI":"10.1128\/mBio.03348-20","article-title":"Evolutionary Divergence in DNA Damage Responses among Fungi","volume":"16","author":"Steenwyk","year":"2021","journal-title":"MBio"},{"key":"ref_67","first-page":"2173","article-title":"Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species","volume":"7","author":"Whaley","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41368-018-0013-2","article-title":"ERG3 and ERG11 genes are critical for the pathogenesis of Candida albicans during the oral mucosal infection","volume":"10","author":"Zhou","year":"2018","journal-title":"Int. J. Oral Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1099\/00221287-148-11-3705","article-title":"Copper- and zinc-containing superoxide dismutase (Cu\/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence","volume":"148","author":"Hwang","year":"2002","journal-title":"Microbiology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/IAI.74.4.2373-2381.2006","article-title":"Deletion of the CaBIG1 gene reduces \u03b2-1,6-Glucan synthesis, filamentation, adhesion, and virulence in Candida albicans","volume":"74","author":"Umeyama","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e01924-17","DOI":"10.1128\/AAC.01924-17","article-title":"Deletion of ADA2 Increases antifungal Drug Susceptibility and Virulence in Candida glabrata","volume":"62","author":"Yu","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1128\/EC.2.6.1266-1273.2003","article-title":"EAP1, a Candida albicans Gene involved in binding human epithelial cells","volume":"2","author":"Li","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1128\/EC.2.1.9-18.2003","article-title":"Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans","volume":"2","author":"Bassilana","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ijmm.2017.09.017","article-title":"The N-terminal pY33XL motif of CaPsy2 is critical for the function of protein phosphatase 4 in CaRad53 deactivation, DNA damage-induced filamentation and virulence in Candida albicans","volume":"307","author":"Feng","year":"2017","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. Rev. Dis. 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