Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms
In 2022, we initiated systematic 5-fluorocytosine susceptibility testing of Candida spp. isolates in Denmark; we observed a bimodal MIC distribution in C. tropicalis, with MICs >16 mg/L in half the isolates. This study investigates the epidemiology and molecular mechanisms of 5-fluorocytosine re...
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Centers for Disease Control and Prevention
2025-05-01
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| Series: | Emerging Infectious Diseases |
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| Online Access: | https://wwwnc.cdc.gov/eid/article/31/5/24-1910_article |
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| author | Nissrine Abou-Chakra Karen Marie Thyssen Astvad Jan Martinussen Amalie Sofie Eilsø Munksgaard Maiken Cavling Arendrup |
| author_facet | Nissrine Abou-Chakra Karen Marie Thyssen Astvad Jan Martinussen Amalie Sofie Eilsø Munksgaard Maiken Cavling Arendrup |
| author_sort | Nissrine Abou-Chakra |
| collection | DOAJ |
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In 2022, we initiated systematic 5-fluorocytosine susceptibility testing of Candida spp. isolates in Denmark; we observed a bimodal MIC distribution in C. tropicalis, with MICs >16 mg/L in half the isolates. This study investigates the epidemiology and molecular mechanisms of 5-fluorocytosine resistance in C. tropicalis. We analyzed 104 C. tropicalis isolates from 3 time periods, alongside 353 C. albicans and 227 C. glabrata isolates from 2022. We determined MICs using EUCAST E.Def 7.3. Sequencing of FCY2 (purine-cytosine permease), FCY1 (cytosine deaminase), FUR1 (uracil phosphoribosyl transferase), and URA3 (orotidine-5′-phosphate decarboxylase) genes revealed FCY2 alterations—E49X (30/32), Q7X (1/32), and K6NfsX10 (1/32)—in resistant C. tropicalis strains. We found a URA3 alteration, K177E, in both susceptible and resistant strains. Microsatellite genotyping showed that all C. tropicalis isolates with E49X were clonally related. The marked increase in resistance, driven by the clonal spread of E49X, necessitates further research into virulence and environmental factors.
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| format | Article |
| id | doaj-art-35e35e1e95464e1981ce5b3e1239d5c4 |
| institution | DOAJ |
| issn | 1080-6040 1080-6059 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Centers for Disease Control and Prevention |
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| series | Emerging Infectious Diseases |
| spelling | doaj-art-35e35e1e95464e1981ce5b3e1239d5c42025-08-20T03:19:11ZengCenters for Disease Control and PreventionEmerging Infectious Diseases1080-60401080-60592025-05-0131597798510.3201/eid3105.241910Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular MechanismsNissrine Abou-ChakraKaren Marie Thyssen AstvadJan MartinussenAmalie Sofie Eilsø MunksgaardMaiken Cavling Arendrup In 2022, we initiated systematic 5-fluorocytosine susceptibility testing of Candida spp. isolates in Denmark; we observed a bimodal MIC distribution in C. tropicalis, with MICs >16 mg/L in half the isolates. This study investigates the epidemiology and molecular mechanisms of 5-fluorocytosine resistance in C. tropicalis. We analyzed 104 C. tropicalis isolates from 3 time periods, alongside 353 C. albicans and 227 C. glabrata isolates from 2022. We determined MICs using EUCAST E.Def 7.3. Sequencing of FCY2 (purine-cytosine permease), FCY1 (cytosine deaminase), FUR1 (uracil phosphoribosyl transferase), and URA3 (orotidine-5′-phosphate decarboxylase) genes revealed FCY2 alterations—E49X (30/32), Q7X (1/32), and K6NfsX10 (1/32)—in resistant C. tropicalis strains. We found a URA3 alteration, K177E, in both susceptible and resistant strains. Microsatellite genotyping showed that all C. tropicalis isolates with E49X were clonally related. The marked increase in resistance, driven by the clonal spread of E49X, necessitates further research into virulence and environmental factors. https://wwwnc.cdc.gov/eid/article/31/5/24-1910_articleantimicrobial resistancefungiflucytosine resistanceCandida tropicalisclonal spreademerging resistance |
| spellingShingle | Nissrine Abou-Chakra Karen Marie Thyssen Astvad Jan Martinussen Amalie Sofie Eilsø Munksgaard Maiken Cavling Arendrup Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms Emerging Infectious Diseases antimicrobial resistance fungi flucytosine resistance Candida tropicalis clonal spread emerging resistance |
| title | Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms |
| title_full | Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms |
| title_fullStr | Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms |
| title_full_unstemmed | Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms |
| title_short | Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms |
| title_sort | exponential clonal expansion of 5 fluorocytosine resistant candida tropicalis and new insights into underlying molecular mechanisms |
| topic | antimicrobial resistance fungi flucytosine resistance Candida tropicalis clonal spread emerging resistance |
| url | https://wwwnc.cdc.gov/eid/article/31/5/24-1910_article |
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