{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:13:58Z","timestamp":1788502438665,"version":"build-2803163510"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"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":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida kefyr<\/jats:named-content>\n            is an increasingly reported pathogen in patients with hematologic malignancies. We studied a series of bloodstream isolates that exhibited reduced echinocandin susceptibilities (RES). Clinical and surveillance isolates were tested for susceptibilities to all three echinocandins, and those isolates displaying RES to one or more echinocandins were selected for molecular and biochemical studies. The isolates were analyzed for genetic similarities, and a subset was analyzed for mutations in the echinocandin target gene\n            <jats:italic>FKS1<\/jats:italic>\n            and glucan synthase echinocandin sensitivities using biochemical methods. The molecular typing did not indicate strong genetic relatedness among the isolates except for a series of strains recovered from a single patient. Two unrelated isolates with RES had previously uncharacterized\n            <jats:italic>FKS1<\/jats:italic>\n            mutations: R647G and deletion of amino acid 641 (F641\u0394). Biochemical analysis of the semipurified R647G glucan synthase generated differential echinocandin sensitivity (resistance to micafungin only), while the deletion of F641 resulted in a glucan synthase highly insensitive to all three echinocandins. The consecutive isolates from a single patient with RES all harbored the common S645P mutation, which conferred resistance to all three echinocandins. The MIC values paralleled the glucan synthase inhibition kinetic data, although the S645P isolates displayed relatively higher susceptibility to caspofungin (2 \u03bcg\/ml) than the other two echinocandins (&gt;8 \u03bcg\/ml). These findings highlight novel and common\n            <jats:italic>FKS1<\/jats:italic>\n            mutations in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. kefyr<\/jats:named-content>\n            isolates. The observation of differential susceptibilities to echinocandins may provide important mechanistic insights for echinocandin antifungals.\n          <\/jats:p>","DOI":"10.1128\/aac.00096-14","type":"journal-article","created":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T14:43:52Z","timestamp":1404225832000},"page":"5421-5427","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Target Enzyme Mutations Confer Differential Echinocandin Susceptibilities in Candida kefyr"],"prefix":"10.1128","volume":"58","author":[{"given":"Janet F.","family":"Staab","sequence":"first","affiliation":[{"name":"Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionysios","family":"Neofytos","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rhee","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Jim\u00e9nez-Ortigosa","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School\u2013Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Perlin","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School\u2013Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieren A.","family":"Marr","sequence":"additional","affiliation":[{"name":"Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA"},{"name":"The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.24.11.1084.36140"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/497079"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/506573"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm145"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2009.06.007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408410903241444"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01590-09"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01653-05"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.11.2471"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00349-06"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3264-3273.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2007.04.002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.19"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02037-12"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00082-12"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.147.1.163"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.24.14604"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01811-10"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00131-14"},{"key":"e_1_3_2_21_2","first-page":"187","article-title":"A systematic study of some Torulas","volume":"22","author":"Harrison FC","year":"1928","unstructured":"HarrisonFC. 1928. 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