{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:49Z","timestamp":1787009029096,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AI132638"],"award-info":[{"award-number":["RO1 AI132638"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Although perceived as a rare clinical entity, recent studies have noted the emergence of MDR C. parapsilosis (MDR-Cp) isolates from single patients (resistant to both azole and echinocandins). We previously reported a case series of MDR-Cp isolates carrying a novel FKS1R658G mutation. Herein, we identified an echinocandin-naive patient infected with MDR-Cp a few months after the previously described isolates. WGS and CRISPR-Cas9 editing were used to explore the origin of the new MDR-Cp isolates, and to determine if the novel mutation confers echinocandin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WGS was applied to assess the clonality of these isolates and CRISPR-Cas9 editing and a Galleria mellonella model were used to examine whether FKS1R658G confers echinocandin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fluconazole treatment failed, and the patient was successfully treated with liposomal amphotericin B (LAMB). WGS proved that all historical and novel MDR-Cp strains were clonal and distant from the fluconazole-resistant outbreak cluster in the same hospital. CRISPR-Cas9 editing and G. mellonella virulence assays confirmed that FKS1R658G confers echinocandin resistance in vitro and in vivo. Interestingly, the FKS1R658G mutant showed a very modest fitness cost compared with the parental WT strain, consistent with the persistence of the MDR-Cp cluster in our hospital.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study showcases the emergence of MDR-Cp isolates as a novel threat in clinical settings, which undermines the efficacy of the two most widely used antifungal drugs against candidiasis, leaving only LAMB as a last resort. Additionally, surveillance studies and WGS are warranted to effectively establish infection control and antifungal stewardship strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkad112","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T20:50:24Z","timestamp":1682542224000},"page":"1488-1494","source":"Crossref","is-referenced-by-count":25,"title":["Whole-genome sequencing confirms a persistent candidaemia clonal outbreak due to multidrug-resistant\n                    <i>Candida parapsilosis<\/i>"],"prefix":"10.1093","volume":"78","author":[{"given":"Farnaz","family":"Daneshnia","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02114 USA"},{"name":"Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam , Amsterdam, 1012 WX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00fcleyha","family":"Hilmio\u011flu-Polat","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Ege University Faculty of Medicine , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1174-4182","authenticated-orcid":false,"given":"Macit","family":"Ilkit","sequence":"additional","affiliation":[{"name":"Division of Mycology, Faculty of Medicine, University of \u00c7ukurova , Adana , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-6786","authenticated-orcid":false,"given":"Diego","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Comparative Genomics group, Life Sciences department, Barcelona Supercomputing Center (BSC-CNS), Carrer de Jordi Girona, 29, 31 , 08034 Barcelona , Spain"},{"name":"Comparative Genomics group, Mechanisms of Disease Programme, Institute for Research in Biomedicine (IRB) , Carrer Baldiri Reixac 10, 08028, Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Lombardi","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield , Dublin , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Binder","sequence":"additional","affiliation":[{"name":"Medical University Innsbruck, Institute of Hygiene and Medical Microbiology , Sch\u00f6pfstrasse 41, 6020 Innsbruck , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Scheler","sequence":"additional","affiliation":[{"name":"Medical University Innsbruck, Institute of Hygiene and Medical Microbiology , Sch\u00f6pfstrasse 41, 6020 Innsbruck , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-1916","authenticated-orcid":false,"given":"Ferry","family":"Hagen","sequence":"additional","affiliation":[{"name":"Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam , Amsterdam, 1012 WX , The Netherlands"},{"name":"Westerdijk Fungal Biodiversity Institute , Utrecht, 3584CT , The Netherlands"},{"name":"Department of Medical Microbiology, University Medical Center Utrecht , Utrecht, 3584CX , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K","family":"Mansour","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital , Boston, MA 02114 USA"},{"name":"Department of Medicine, Harvard Medical School , Boston, MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-5301","authenticated-orcid":false,"given":"Geraldine","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield , Dublin , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Lass-Fl\u00f6rl","sequence":"additional","affiliation":[{"name":"Medical University Innsbruck, Institute of Hygiene and Medical Microbiology , Sch\u00f6pfstrasse 41, 6020 Innsbruck , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Gabaldon","sequence":"additional","affiliation":[{"name":"Comparative Genomics group, Life Sciences department, Barcelona Supercomputing Center (BSC-CNS), Carrer de Jordi Girona, 29, 31 , 08034 Barcelona , Spain"},{"name":"Comparative Genomics group, Mechanisms of Disease Programme, Institute for Research in Biomedicine (IRB) , Carrer Baldiri Reixac 10, 08028, Barcelona , Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Pg. 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