{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:50:15Z","timestamp":1790725815814,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antifungal flucytosine (5-fluorocytosine [5FC]) is a prodrug metabolized to its toxic form, 5-fluorouracil (5FU), only by organisms expressing cytosine deaminase. One such organism is\n            <jats:italic>Candida glabrata<\/jats:italic>\n            , which has emerged as the second most common agent of bloodstream and mucosal candidiasis. This emergence has been attributed to the high rate at which\n            <jats:italic>C. glabrata<\/jats:italic>\n            develops resistance to azole antifungals. As an oral agent, 5FC represents an attractive alternative or complement to azoles; however, the frequency of 5FC resistance mutations and the mechanisms by which these mutations confer resistance have been explored only minimally. On RPMI 1640 medium containing 1 \u03bcg\/ml 5FC (32-fold above the MIC, but less than 1\/10 of typical serum levels), resistant mutants occurred at a relatively low frequency (2 \u00d7 10\n            <jats:sup>\u22127<\/jats:sup>\n            ). Three of six mutants characterized were 5FU cross-resistant, suggesting a mutation downstream of the Fcy1 gene (cytosine deaminase), which was confirmed by sequence analysis of the Fur1 gene (uracil phosphoribosyl transferase). The remaining three mutants had Fcy1 mutations. To ascertain the effects of 5FC resistance mutations on enzyme function, mutants were isolated in\n            <jats:italic>ura3<\/jats:italic>\n            strains. Three of seven mutants harbored Fcy1 mutations and failed to grow in uridine-free, cytosine-supplemented medium, consistent with inactive Fcy1. The remainder grew in this medium and had wild-type Fcy1; further analysis revealed these to be mutated in the Fcy2L homolog of\n            <jats:italic>S. cerevisiae<\/jats:italic>\n            Fcy2 (purine-cytosine transporter). Based on this analysis, we characterized three 5FC-resistant clinical isolates, and mutations were identified in Fur1 and Fcy1. These data provide a framework for understanding 5FC resistance in\n            <jats:italic>C. glabrata<\/jats:italic>\n            and potentially in other fungal pathogens.\n          <\/jats:p>","DOI":"10.1128\/aac.00605-10","type":"journal-article","created":{"date-parts":[[2010,9,8]],"date-time":"2010-09-08T02:45:29Z","timestamp":1283913929000},"page":"4733-4738","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["Mutational Analysis of Flucytosine Resistance in\n            <i>Candida glabrata<\/i>"],"prefix":"10.1128","volume":"54","author":[{"given":"Thomas D.","family":"Edlind","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh K.","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01138-09"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.6.2223-2227.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002940050169"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-136-8-1475"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00880-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00443-09"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4377-4386.2004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(03)00153-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.102.3.607-615.1970"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00020-09"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(90)90026-N"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309592"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300874200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-003-0373-8"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4315"},{"key":"e_1_3_2_17_2","first-page":"1732","volume":"25","year":"2009","unstructured":"Lewis, R. E. 2009. Overview of the changing epidemiology of candidemia. Curr. Med. Res. Opin.25:1732-1740.","journal-title":"Curr. Med. Res. Opin."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600304"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00607-09"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.1387"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00029-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3518-3521.2002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.5.2163-2167.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.262-266.2004"},{"key":"e_1_3_2_25_2","first-page":"63","volume":"21","year":"2004","unstructured":"Quind\u00f3s, G., M. T. Ruesga, E. Mart\u00edn-Mazuelos, R. Salesa, R. Alonso-Vargas, A. J. Carrillo-Mu\u00f1oz, S. Brena, R. San Mill\u00e1n, and J. Pont\u00f3n. 2004. In-vitro activity of 5-fluorocytosine against 1,021 Spanish clinical isolates of Candida and other medically important yeasts. Rev. Iberoam. Micol.21:63-69.","journal-title":"Rev. Iberoam. Micol."},{"key":"e_1_3_2_26_2","first-page":"2155","volume":"30","year":"2005","unstructured":"Richter, S. S., R. P. Galask, S. A. Messer, R. J. Hollis, D. J. Diekema, and M. A. Pfaller. 2005. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J. Clin. Microbiol.30:2155-2162.","journal-title":"J. Clin. 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