{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:27:51Z","timestamp":1789586871904,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Candidozyma auris (formerly known as Candida auris) has emerged as a formidable clinical fungal pathogen as a result of its multidrug resistance and persistent colonization capabilities. In this study, three clinical C. auris strains (namely C. auris strain 01, C. auris strain 03, and C. auris strain 13) with distinct origins were characterized to investigate their phenotypic variations and mechanisms of azole resistance. Comprehensive profiling revealed significant inter-strain differences in biofilm formation, cell surface hydrophobicity, adhesion capacity, and phospholipase activity. Testing for antifungal susceptibility showed that the three clinical strains exhibited different minimum inhibitory concentrations for multiple azoles (fluconazole, voriconazole, and itraconazole) and echinocandins (anidulafungin and micafungin). Sequencing identified Y132F mutations in the ERG11 gene of the three clinical strains. Mechanistic investigations demonstrated that fluconazole exposure significantly upregulated the expression of efflux pump genes (CDR1 and CDR2) and the genes encoding their transcriptional regulators (MDR1 and TAC1b). In a murine skin colonization model, comparing data from the standard strain C. auris strain CBS12766 and clinical strains of C. auris strain 03 and C. auris strain 13 exhibited a significantly higher fungal burden of tissue, whereas strain C. auris strain 01 showed an intermediate level. Host immunity response analysis revealed that expression of the IL-1\u03b2 gene was significantly elevated in C. auris strain CBS12766-infected mice, while expression of IL-6 and CXCL-1 genes was predominantly increased in the C. auris strain 01, with TNF-\u03b1 gene expression levels being comparable across all strains. Histopathological examination confirmed local infiltration of inflammatory cells and mild epidermal edema, indicating active host immune engagement. Overall, our findings highlighted substantial phenotypic heterogeneity, different colonization capacities, and differences in expression of inflammatory cytokines among the C. auris strains. Further investigations into fluconazole-response mechanisms identified enhanced efflux pump activity, along with ERG11 gene Y132F mutations and transcription factor modulation among these clinical strains.<\/jats:p>","DOI":"10.3390\/microorganisms14071400","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"1400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Analysis of Virulence Traits and Fluconazole-Response Mechanisms in Clinical Isolates of Candidozyma auris"],"prefix":"10.3390","volume":"14","author":[{"given":"Cai","family":"Hu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyan","family":"Xin","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-485X","authenticated-orcid":false,"given":"Zhangyong","family":"Song","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China"},{"name":"Public Center of Experimental Technology, Southwest Medical University, Luzhou 646000, China"},{"name":"Hemodynamics and Medical Engineering Combination Key Laboratory of Luzhou, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s42770-023-01239-0","article-title":"Current global status of Candida auris an emerging multidrug-resistant fungal pathogen: Bibliometric analysis and network visualization","volume":"55","author":"Ettadili","year":"2024","journal-title":"Braz. J. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e0012724","DOI":"10.1128\/spectrum.00127-24","article-title":"Intradermal infection and dissemination of Candida auris in immunocompetent and immunocompromised mouse models","volume":"12","author":"Towns","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"myae042","DOI":"10.1093\/mmy\/myae042","article-title":"Candida auris-a systematic review to inform the world health organization fungal priority pathogens list","volume":"62","author":"Kim","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chowdhary, A., Sharma, C., and Meis, J.F. (2017). Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006290"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1080\/21505594.2021.1908765","article-title":"Virulence of Candida auris from different clinical origins in Caenorhabditis elegans and Galleria mellonella host models","volume":"12","author":"Mateo","year":"2021","journal-title":"Virulence"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/myc.13022","article-title":"Candida auris in various hospitals across Kuwait and their susceptibility and molecular basis of resistance to antifungal drugs","volume":"63","author":"Ahmad","year":"2020","journal-title":"Mycoses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"dlaf106","DOI":"10.1093\/jacamr\/dlaf106","article-title":"Understanding the mechanisms of resistance to azole antifungals in Candida species","volume":"7","author":"Li","year":"2025","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fr\u00edas-De-Le\u00f3n, M.G., Hern\u00e1ndez-Castro, R., Vite-Gar\u00edn, T., Arenas, R., Bonifaz, A., Casta\u00f1\u00f3n-Olivares, L., Acosta-Altamirano, G., and Mart\u00ednez-Herrera, E. (2020). Antifungal Resistance in Candida auris: Molecular Determinants. Antibiotics, 9.","DOI":"10.3390\/antibiotics9090568"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e01427-18","DOI":"10.1128\/AAC.01427-18","article-title":"Limited ERG11 Mutations Identified in Isolates of Candida auris Directly Contribute to Reduced Azole Susceptibility","volume":"62","author":"Healey","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wasi, M., Khandelwal, N.K., Moorhouse, A.J., Nair, R., Vishwakarma, P., Bravo Ruiz, G., Ross, Z.K., Lorenz, A., Rudramurthy, S.M., and Chakrabarti, A. (2019). ABC Transporter Genes Show Upregulated Expression in Drug-Resistant Clinical Isolates of Candida auris: A Genome-Wide Characterization of ATP-Binding Cassette (ABC) Transporter Genes. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01445"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e0006722","DOI":"10.1128\/aac.00067-22","article-title":"Deciphering the Mrr1\/Mdr1 Pathway in Azole Resistance of Candida auris","volume":"66","author":"Li","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e02663-20","DOI":"10.1128\/AAC.02663-20","article-title":"Novel ERG11 and TAC1b mutations associated with azole resistance in Candida auris","volume":"65","author":"Li","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-med-061523-021233","article-title":"Candida auris: Epidemiology and Antifungal Strategy","volume":"76","author":"Eix","year":"2025","journal-title":"Annu. Rev. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0240624","DOI":"10.1128\/aem.02406-24","article-title":"Comparative analyses of the biological characteristics, fluconazole resistance, and heat adaptation mechanisms of Candida auris and members of the Candida haemulonii complex","volume":"91","author":"Xiao","year":"2025","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Carolus, H., Jacobs, S., Lobo Romero, C., Deparis, Q., Cuomo, C.A., Meis, J.F., and Van Dijck, P. (2021). Diagnostic Allele-Specific PCR for the Identification of Candida auris Clades. J. Fungi, 7.","DOI":"10.3390\/jof7090754"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127200","DOI":"10.1016\/j.micres.2022.127200","article-title":"Antifungal activity of vitamin D3 against Candida albicans in vitro and in vivo","volume":"265","author":"Lei","year":"2022","journal-title":"Microbiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11046-025-01008-7","article-title":"Character Virulence Association Factors and Gene Mutation Mediating Multidrug Resistance Phenotypes in Candidozyma duobushaemulonii","volume":"190","author":"Zhou","year":"2025","journal-title":"Mycopathologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0221523","DOI":"10.1128\/spectrum.02215-23","article-title":"Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans","volume":"11","author":"Datta","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12964-020-00532-x","article-title":"TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection","volume":"18","author":"Bai","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11046-025-00945-7","article-title":"Deciphering Fluconazole Resistance in Candida auris clade V: The Role of Efflux Pump Gene Expression and Ergosterol Pathway Mutations","volume":"190","author":"Abastabar","year":"2025","journal-title":"Mycopathologia"},{"key":"ref_21","unstructured":"Centers for Disease Control and Prevention (2026, June 03). Antifungal Susceptibility Testing for Candida auris. CDC Website, Available online: https:\/\/www.cdc.gov\/candida-auris\/hcp\/laboratories\/antifungal-susceptibility-testing.html."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26213","DOI":"10.1038\/srep26213","article-title":"Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14\u03b1-demethylase","volume":"6","author":"Sagatova","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1056\/NEJMra2402635","article-title":"Candida auris Infections","volume":"391","author":"Lionakis","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ortiz-Roa, C., Valderrama-Rios, M.C., Sierra-Uma\u00f1a, S.F., Rodr\u00edguez, J.Y., Mu\u00f1et\u00f3n-L\u00f3pez, G.A., Sol\u00f3rzano-Ramos, C.A., Escand\u00f3n, P., Alvarez-Moreno, C.A., and Cort\u00e9s, J.A. (2023). Mortality Caused by Candida auris Bloodstream Infections in Comparison with Other Candida Species, a Multicentre Retrospective Cohort. J. Fungi, 9.","DOI":"10.3390\/jof9070715"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13756-016-0132-5","article-title":"First hospital outbreak of the globally emerging Candida auris in a European hospital","volume":"5","author":"Schelenz","year":"2016","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40588-020-00143-7","article-title":"Candida auris infection and biofilm formation: Going beyond the surface","volume":"7","author":"Horton","year":"2020","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1093\/cid\/ciad752","article-title":"Rapid Environmental Contamination with Candida auris and Multidrug-Resistant Bacterial Pathogens Near Colonized Patients","volume":"75","author":"Sansom","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1038\/s41467-022-31201-x","article-title":"Innate immune responses against the fungal pathogen Candida auris","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1128\/EC.4.4.633-638.2005","article-title":"Candida biofilms: An update","volume":"4","author":"Ramage","year":"2025","journal-title":"Eukaryot. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2174\/1389203720666190722152415","article-title":"Virulence Factors in Candida species","volume":"21","author":"Staniszewska","year":"2020","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00189-16","DOI":"10.1128\/mSphere.00189-16","article-title":"Comparative Pathogenicity of United Kingdom Isolates of the Emerging Pathogen Candida auris and Other Key Pathogenic Candida Species","volume":"1","author":"Borman","year":"2016","journal-title":"mSphere"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bhargava, A., Klamer, K., Sharma, M., Ortiz, D., and Saravolatz, L. (2025). Candida auris: A Continuing Threat. Microorganisms, 13.","DOI":"10.3390\/microorganisms13030652"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Phan-Canh, T., and Kuchler, K. (2024). Do morphogenetic switching and intraspecies variation enhance virulence of Candida auris?. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012559"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"myad127","DOI":"10.1093\/mmy\/myad127","article-title":"Review of treatment options for a multidrug-resistant fungus: Candida auris","volume":"62","author":"Wang","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Du, H., Bing, J., Hu, T., Ennis, C.L., Nobile, C.J., and Huang, G. (2020). Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008921"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00057-19","DOI":"10.1128\/AAC.00057-19","article-title":"Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris","volume":"63","author":"Rybak","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00365-20","DOI":"10.1128\/mBio.00365-20","article-title":"Mutations in TAC1B: A Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris","volume":"11","author":"Rybak","year":"2020","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0158521","DOI":"10.1128\/Spectrum.01585-21","article-title":"Delineation of the Direct Contribution of Candida auris ERG11 Mutations to Clinical Triazole Resistance","volume":"9","author":"Rybak","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102208","DOI":"10.1016\/j.mib.2022.102208","article-title":"The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris","volume":"70","author":"Rybak","year":"2022","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.micpath.2018.09.014","article-title":"Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options","volume":"125","author":"Silva","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1038\/s41564-020-0780-3","article-title":"Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris","volume":"5","author":"Bruno","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chom.2020.12.002","article-title":"Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies","volume":"29","author":"Huang","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3390\/toxics9040072","article-title":"Inflammatory Biomarkers Interleukin 1 Beta (IL-1\u03b2) and Tumour Necrosis Factor Alpha (TNF-\u03b1) Are Differentially Elevated in Tobacco Smoke Associated COPD and Biomass Smoke Associated COPD","volume":"9","author":"Chaya","year":"2021","journal-title":"Toxics"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Burgess, T.B., Condliffe, A.M., and Elks, P.M. (2022). A Fun-Guide to Innate Immune Responses to Fungal Infections. J. Fungi, 8.","DOI":"10.3390\/jof8080805"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Santana, D.J., Zhao, G., and O\u2019Meara, T.R. (2024). The many faces of Candida auris: Phenotypic and strain variation in an emerging pathogen. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012011"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:11:18Z","timestamp":1783311078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/7\/1400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["microorganisms14071400"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14071400","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}