{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:13:18Z","timestamp":1791511998780,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81861148028"],"award-info":[{"award-number":["81861148028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971912"],"award-info":[{"award-number":["81971912"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangxi Province of China project Guangxi Innovation Research Team for Fungal Infectious Diseases Prevention and Treatment","award":["2020GXNSFGA238001"],"award-info":[{"award-number":["2020GXNSFGA238001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Candida glabrata is one of the most prevalent causative pathogens of invasive candidiasis, and multidrug-resistant strains are emerging. We identified two clinical isolates of C. glabrata, BMU10720 and BMU10722 sequentially isolated from one patient with multidrug-resistance to posaconazole (POS), caspofungin (CAS), micafungin (MCF), and anidulafungin (ANF). Overexpression of ERG11 in BMU10720 and CDR1 in BMU10722 were detected at basal level. When exposed to POS, CDR1 was significantly up-regulated in both isolates compared with susceptible reference strain, while ERG11 was up-regulated considerably only in BMU10720. PDR1 sequencing revealed that both isolates harbored P76S, P143T, and D243N substitutions, while ERG11 was intact. Cdr1 inhibitor FK520 reversed POS-resistance by down-regulating ERG11 expression. FKS sequencing revealed that both isolates harbored S663P substitution in FKS2, and four single nucleotide polymorphisms (SNPs) existed in FKS2 genes between BMU10720 and BMU10722, while FKS1 was intact. Both FKS1 and FKS2 were up-regulated by CAS in BMU10720 and BMU10722. FK520 down-regulated FKS2 expression induced by CAS through inhibiting calcineurin, resulting in synergic effect with echinocandins as well as Congo Red and Calcofluor White, two cell wall-perturbing agents. In conclusion, the multidrug-resistance of C. glabrata isolates in our study was conferred by different mechanisms. CDR1 and ERG11 overexpression in one isolate and only CDR1 overexpression in the other isolate may mediate POS-resistance. S663P mutation in FKS2 and up-regulation of FKS2 may contribute to echinocandin-resistance in both isolates.<\/jats:p>","DOI":"10.3390\/antibiotics10101217","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"1217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Two Sequential Clinical Isolates of Candida glabrata with Multidrug-Resistance to Posaconazole and Echinocandins"],"prefix":"10.3390","volume":"10","author":[{"given":"Qiqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-2737","authenticated-orcid":false,"given":"Ence","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing 100034, China"},{"name":"Research Center for Medical Mycology, Peking University, Beijing 100034, China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18026","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive Candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. 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