{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:01Z","timestamp":1787028721029,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Fluconazole-resistant Candida parapsilosis has emerged as a significant nosocomial pathogen, contributing to extensive outbreaks with severe clinical implications. Despite increasing evidence of clonal transmission, the genetic mechanisms that facilitate the persistence of hospital reservoirs remain inadequately characterized. We aimed to characterise the long-term molecular epidemiology of fluconazole-resistant Candida parapsilosis bloodstream isolates (n = 47) collected between 1997 and 2019 at a tertiary centre. All isolates underwent microsatellite analysis using three polymorphic markers (CP1, CP4, B5). Genetic diversity, temporal distribution, and clonal relationships were assessed through phylogenetic analysis and discriminatory power calculations. Microsatellite analysis revealed minimal genetic diversity (combined discriminatory power: 0.7114), with only six distinct genotypes identified. Two dominant clones (Genotype-1: 23.4%, Genotype-2: 46.8%) persisted throughout the study, showing apparent spatiotemporal clustering in surgical and intensive care units. Phylogenetic analysis demonstrated tight genetic clustering, consistent with prolonged clonal persistence across multiple years and clinical departments. Our findings provide strong molecular evidence consistent with persistent, multi-year clonal transmission; however, definitive confirmation will require higher-resolution genomics and epidemiologic linkage. These results underscore the need to strengthen infection-control practices to curtail sustained clonal persistence within the hospital.<\/jats:p>","DOI":"10.3390\/jof11110802","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:56:47Z","timestamp":1762945007000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Silent Persistence: Molecular Evidence of Clonal Transmission in Fluconazole-Resistant Candida parapsilosis Hospital Outbreaks over Decades"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-820X","authenticated-orcid":false,"given":"Cihan","family":"Semet","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-2501","authenticated-orcid":false,"given":"Esra","family":"Kazak","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-9755","authenticated-orcid":false,"given":"Se\u00e7il","family":"Ak-Aksoy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-2034","authenticated-orcid":false,"given":"Harun","family":"A\u011fca","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-8206","authenticated-orcid":false,"given":"Beyza","family":"Ener","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Bursa Uluda\u011f University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.5455\/ijmsph.2016.24082015139","article-title":"Study of biofilm formation as a virulence marker in Candida species isolated from various clinical specimens","volume":"5","author":"Sida","year":"2015","journal-title":"Int. J. Med. Sci. Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.18535\/jmscr\/v6i4.127","article-title":"Characterization of Candida Species isolated from samples taken from patients with known Immunocompromised state presenting with Oral Thrush","volume":"6","author":"Mukul","year":"2018","journal-title":"J. Med. Sci. Clin. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s40560-018-0342-4","article-title":"Epidemiology, clinical characteristics, resistance, and treatment of infections by Candida auris","volume":"6","author":"Cortegiani","year":"2018","journal-title":"J. Intensive Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"myad131","DOI":"10.1093\/mmy\/myad131","article-title":"Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list","volume":"62","author":"Asogan","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e280","DOI":"10.1016\/S1473-3099(24)00749-7","article-title":"Global guideline for the diagnosis and management of candidiasis: An initiative of the ECMM in cooperation with ISHAM and ASM","volume":"25","author":"Cornely","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e0098623","DOI":"10.1128\/aac.00986-23","article-title":"Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): Fluconazole-resistant C. parapsilosis spreading has gained traction in 2022","volume":"67","author":"Machado","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/mmy\/myac072.P019","article-title":"P019 A 5-year study on prevalence and molecular determinants of fluconazole resistance in C. parapsilosis spp. complex","volume":"60","author":"Sharma","year":"2022","journal-title":"Med. Mycol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70000","DOI":"10.1111\/myc.70000","article-title":"Multicentre Study of Candida parapsilosis Blood Isolates in T\u00fcrkiye Highlights an Increasing Rate of Fluconazole Resistance and Emergence of Echinocandin and Multidrug Resistance","volume":"67","author":"Spruijtenburg","year":"2024","journal-title":"Mycoses"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Prigitano, A., Blasi, E., Calabr\u00f2, M., Cavanna, C., Cornetta, M., Farina, C., Grancini, A., Innocenti, P., Cascio, G.L., and Nicola, L. (2023). Yeast bloodstream infections in the COVID-19 patient: A multicenter Italian study (FICOV study). J. Fungi, 9.","DOI":"10.3390\/jof9020277"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0732-8893(98)00006-6","article-title":"Candida parapsilosis Fungemia Associated with Implantable and Semi-Implantable Central Venous Catheters and the Hands of Healthcare Workers","volume":"30","author":"Levin","year":"1998","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.1016\/j.jhin.2018.06.009","article-title":"Nosocomial outbreak of Candida parapsilosis sensu stricto fungaemia in a neonatal intensive care unit in China","volume":"100","author":"Qi","year":"2018","journal-title":"J. Hosp. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cacaci, M., Squitieri, D., Palmieri, V., Torelli, R., Perini, G., Campolo, M., Di Vito, M., Papi, M., Posteraro, B., and Sanguinetti, M. (2023). Curcumin-Functionalized Graphene Oxide Strongly Prevents Candida parapsilosis Adhesion and Biofilm Formation. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020275"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00451-18","DOI":"10.1128\/mBio.00451-18","article-title":"Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control","volume":"9","author":"Dominguez","year":"2018","journal-title":"mBio"},{"key":"ref_14","first-page":"e02036-20","article-title":"Hospital Outbreak of Fluconazole-Resistant Candida parapsilosis: Arguments for Clonal Transmission and Long-Term Persistence","volume":"95","author":"Fekkar","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/0002-9343(93)90207-6","article-title":"Nosocomial acquisition of Candida parapsilosis: An epidemiologic study","volume":"94","author":"Sanchez","year":"1993","journal-title":"Am. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1128\/JCM.40.7.2363-2369.2002","article-title":"Horizontal Transmission of Candida parapsilosis Candidemia in a Neonatal Intensive Care Unit","volume":"40","author":"Lupetti","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Asadzadeh, M., Ahmad, S., Al-Sweih, N., Hagen, F., Meis, J.F., and Khan, Z. (2019). High-resolution fingerprinting of Candida parapsilosis isolates suggests persistence and transmission of infections among neonatal intensive care unit patients in Kuwait. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37855-2"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Thomaz, D.Y., Del Negro, G.M.B., Ribeiro, L.B., Da Silva, M., Carvalho, G.O.M.H., Camargo, C.H., de Almeida, J.N., Motta, A.L., Siciliano, R.F., and Sejas, O.N.E. (2022). A Brazilian Inter-Hospital Candidemia Outbreak Caused by Fluconazole-Resistant Candida parapsilosis in the COVID-19 Era. J. Fungi, 8.","DOI":"10.3390\/jof8020100"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"954.e1","DOI":"10.1016\/j.cmi.2015.06.001","article-title":"Analysis of clinical and environmental Candida parapsilosis isolates by microsatellite genotyping\u2014A tool for hospital infection surveillance","volume":"21","author":"Sabino","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_20","first-page":"61","article-title":"Identification of Candida parapsilosis Complex Strains Isolated from Blood Samples at Species Level and Determination of Their Antifungal Susceptibilities","volume":"49","author":"Cilo","year":"2019","journal-title":"T\u00fcrk Mikrobiyoloji Cemiy. Derg."},{"key":"ref_21","unstructured":"CLSI (2017). Reference Method for Broth Dilution Antifungal Susceptibility of Yeasts, Clinical and Laboratory Standards Institute. [4th ed.]. CLSI Standard M27."},{"key":"ref_22","unstructured":"CLSI (2022). Performance Standards for Antifungal Susceptibility of Yeasts, Clinical and Laboratory Standards Institute. [3rd ed.]. CLSI supplement M27M44S."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11046-018-0278-1","article-title":"Molecular Genotyping of Candida parapsilosis Species Complex","volume":"183","author":"Neji","year":"2018","journal-title":"Mycopathologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01001-20","DOI":"10.1128\/AAC.01001-20","article-title":"First Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and\/or Y132F+K143R in Turkey","volume":"64","author":"Arastehfar","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1128\/JCM.02151-09","article-title":"New Polymorphic Microsatellite Markers Able to Distinguish among Candida parapsilosis Sensu Stricto Isolates","volume":"48","author":"Sabino","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1128\/jcm.28.9.1903-1905.1990","article-title":"Reproducibility and indices of discriminatory power of microbial typing methods","volume":"28","author":"Hunter","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","unstructured":"WHO (2022). WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action, World Health Organization."},{"key":"ref_28","first-page":"381","article-title":"Population Structure of Candida parapsilosis: No Genetic Difference Between French and Uruguayan Isolates Using Microsatellite Length Polymorphism","volume":"183","author":"Poirier","year":"2017","journal-title":"Mycopathologia"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Escribano, P., and Guinea, J. (2022). Fluconazole-resistant Candida parapsilosis: A new emerging threat in the fungi arena. Front. Fungal Biol., 3.","DOI":"10.3389\/ffunb.2022.1010782"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"McTaggart, L.R., Eshaghi, A., Hota, S., Poutanen, S.M., Johnstone, J., De Luca, D.G., Bharat, A., Patel, S.N., and Kus, J.V. (2024). First Canadian report of transmission of fluconazole-resistant Candida parapsilosis within two hospital networks confirmed by genomic analysis. J. Clin. Microbiol., 62.","DOI":"10.1128\/jcm.01161-23"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00111-18","DOI":"10.1128\/CMR.00111-18","article-title":"Candida parapsilosis: From Genes to the Bedside","volume":"32","author":"Nosek","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/j.meegid.2012.06.012","article-title":"Genotyping of Candida parapsilosis from three neonatal intensive care units (NICUs) using a panel of five multilocus microsatellite markers: Broad genetic diversity and a cluster of related strains in one NICU","volume":"12","author":"Reiss","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, L., Yu, S.-Y., Chen, S.C., Xiao, M., Kong, F., Wang, H., Ning, Y.-T., Lu, M.-Y., Sun, T.-S., and Hou, X. (2020). Molecular Characterization of Candida parapsilosis by Microsatellite Typing and Emergence of Clonal Antifungal Drug Resistant Strains in a Multicenter Surveillance in China. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01320"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.meegid.2012.09.006","article-title":"Microsatellite-based genotyping of Candida parapsilosis sensu stricto isolates reveals dominance and persistence of a particular epidemiological clone among neonatal intensive care unit patients","volume":"13","author":"Romeo","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_35","first-page":"783","article-title":"Outbreak of Candida parapsilosis in a neonatal intensive care unit: A health care workers source","volume":"169","year":"2009","journal-title":"Eur. J. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e000992","DOI":"10.1136\/bmjopen-2012-000992","article-title":"Candida parapsilosis candidaemia in a neonatal unit over 7 years: A case series study","volume":"2","author":"Miranda","year":"2012","journal-title":"BMJ Open"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1590\/S1413-86702008000500010","article-title":"Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit","volume":"12","author":"Dizbay","year":"2008","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.diagmicrobio.2010.07.004","article-title":"Molecular epidemiology and antifungal susceptibility of Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis in Taiwan","volume":"68","author":"Chen","year":"2010","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1016\/S2666-5247(23)00067-8","article-title":"Worldwide emergence of fluconazole-resistant Candida parapsilosis: Current framework and future research roadmap","volume":"4","author":"Daneshnia","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.jiph.2024.04.009","article-title":"Genotypic and phenotypic characteristics of Candida parapsilosis bloodstream isolates: Health Care Associated Infections in a teaching Hospital in Italy","volume":"17","author":"Caggiano","year":"2024","journal-title":"J. Infect. Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1128\/JCM.44.5.1681-1685.2006","article-title":"Epidemiology, Risk Factors, and Prognosis of Candida parapsilosis Bloodstream Infections: Case-Control Population-Based Surveillance Study of Patients in Barcelona, Spain, from 2002 to 2003","volume":"44","author":"Almirante","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Miyake, A., Gotoh, K., Iwahashi, J., Togo, A., Horita, R., Miura, M., Kinoshita, M., Ohta, K., Yamashita, Y., and Watanabe, H. (2022). Characteristics of Biofilms Formed by C. parapsilosis Causing an Outbreak in a Neonatal Intensive Care Unit. J. Fungi, 8.","DOI":"10.3390\/jof8070700"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Arastehfar, A., Hilmio\u011flu-Polat, S., Daneshnia, F., Pan, W., Hafez, A., Fang, W., Liao, W., \u015eahbudak-Bal, Z., Metin, D.Y., and De Almeida, J.N. (2021). Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.676177"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s00134-017-4743-y","article-title":"The risk and clinical outcome of candidemia depending on underlying malignancy","volume":"43","author":"Lortholary","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1007\/s10096-012-1642-6","article-title":"MALDI-TOF mass spectrometry and microsatellite markers to evaluate Candida parapsilosis transmission in neonatal intensive care units","volume":"31","author":"Pulcrano","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/myc.12596","article-title":"Detection of neonatal unit clusters of Candida parapsilosis fungaemia by microsatellite genotyping: Results from laboratory-based sentinel surveillance, South Africa, 2009\u20132010","volume":"60","author":"Magobo","year":"2017","journal-title":"Mycoses"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Brunetti, G., Navazio, A., Giuliani, A., Giordano, A., Proli, E., Antonelli, G., and Raponi, G. (2019). Candida blood stream infections observed between 2011 and 2016 in a large Italian University Hospital: A time-based retrospective analysis on epidemiology, biofilm production, antifungal agents consumption and drug-susceptibility. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224678"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jinf.2015.09.041","article-title":"Impact of antifungal prescription on relative distribution and susceptibility of Candida spp.\u2014Trends over 10 years","volume":"72","author":"Bailly","year":"2016","journal-title":"J. Infect."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/11\/11\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:31:53Z","timestamp":1762947113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/11\/11\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jof11110802"],"URL":"https:\/\/doi.org\/10.3390\/jof11110802","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]}}}