{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:44:06Z","timestamp":1784025846341,"version":"3.55.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["HEALTH-F3-2013-601963"],"award-info":[{"award-number":["HEALTH-F3-2013-601963"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["FWF J3651-B22"],"award-info":[{"award-number":["FWF J3651-B22"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M02010X\/1"],"award-info":[{"award-number":["MR\/M02010X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RCUK | Medical Research Council","award":["MR\/L000822\/1"],"award-info":[{"award-number":["MR\/L000822\/1"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antifungal drug 5-flucytosine (5FC), a derivative of the nucleobase cytosine, is licensed for the treatment of fungal diseases; however, it is rarely used as a monotherapeutic to treat\n            <jats:named-content content-type=\"genus-species\">Aspergillus<\/jats:named-content>\n            infection. Despite being potent against other fungal pathogens, 5FC has limited activity against\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            when standard\n            <jats:italic>in vitro<\/jats:italic>\n            assays are used to determine susceptibility. However, in modified\n            <jats:italic>in vitro<\/jats:italic>\n            assays where the pH is set to pH 5, the activity of 5FC increases significantly. Here we provide evidence that\n            <jats:italic>fcyB<\/jats:italic>\n            , a gene that encodes a purine-cytosine permease orthologous to known 5FC importers, is downregulated at pH 7 and is the primary factor responsible for the low efficacy of 5FC at pH 7. We also uncover two transcriptional regulators that are responsible for the repression of\n            <jats:italic>fcyB<\/jats:italic>\n            and, consequently, mediators of 5FC resistance, the CCAAT binding complex (CBC) and the pH regulatory protein PacC. We propose that the activity of 5FC might be enhanced by the perturbation of factors that repress\n            <jats:italic>fcyB<\/jats:italic>\n            expression, such as PacC or other components of the pH-sensing machinery.\n          <\/jats:p>","DOI":"10.1128\/aac.02593-17","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T13:27:06Z","timestamp":1522330026000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Mechanistic Basis of pH-Dependent 5-Flucytosine Resistance in Aspergillus fumigatus"],"prefix":"10.1128","volume":"62","author":[{"given":"Fabio","family":"Gsaller","sequence":"first","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"},{"name":"Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Carr","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Rash","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"J\u00f6chl","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Bertuzzi","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine M.","family":"Bignell","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bromley","sequence":"additional","affiliation":[{"name":"Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Core Technology Facility, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/179663a0"},{"key":"e_1_3_3_3_2","first-page":"566","article-title":"Chemotherapeutic activity of 5-fluorocytosine","volume":"161","author":"Grunberg E","year":"1963","unstructured":"Grunberg E, Titsworth E, Bennett M. 1963. 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