Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins
<i>Candida glabrata</i> is one of the most prevalent causative pathogens of invasive candidiasis, and multidrug-resistant strains are emerging. We identified two clinical isolates of <i>C. glabrata</i>, BMU10720 and BMU10722 sequentially isolated from one patient with multidr...
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MDPI AG
2021-10-01
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| author | Qiqi Wang Yun Li Xuan Cai Ruoyu Li Bo Zheng Ence Yang Tianyu Liang Xinyu Yang Zhe Wan Wei Liu |
| author_facet | Qiqi Wang Yun Li Xuan Cai Ruoyu Li Bo Zheng Ence Yang Tianyu Liang Xinyu Yang Zhe Wan Wei Liu |
| author_sort | Qiqi Wang |
| collection | DOAJ |
| description | <i>Candida glabrata</i> is one of the most prevalent causative pathogens of invasive candidiasis, and multidrug-resistant strains are emerging. We identified two clinical isolates of <i>C. glabrata</i>, BMU10720 and BMU10722 sequentially isolated from one patient with multidrug-resistance to posaconazole (POS), caspofungin (CAS), micafungin (MCF), and anidulafungin (ANF). Overexpression of <i>ERG11</i> in BMU10720 and <i>CDR1</i> in BMU10722 were detected at basal level. When exposed to POS, <i>CDR1</i> was significantly up-regulated in both isolates compared with susceptible reference strain, while <i>ERG11</i> was up-regulated considerably only in BMU10720. <i>PDR1</i> sequencing revealed that both isolates harbored P76S, P143T, and D243N substitutions, while <i>ERG11</i> was intact. Cdr1 inhibitor FK520 reversed POS-resistance by down-regulating <i>ERG11</i> expression. <i>FKS</i> sequencing revealed that both isolates harbored S663P substitution in <i>FKS2</i>, and four single nucleotide polymorphisms (SNPs) existed in <i>FKS2</i> genes between BMU10720 and BMU10722, while <i>FKS1</i> was intact. Both <i>FKS1</i> and <i>FKS2</i> were up-regulated by CAS in BMU10720 and BMU10722. FK520 down-regulated <i>FKS2</i> 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 <i>C. glabrata</i> isolates in our study was conferred by different mechanisms. <i>CDR1</i> and <i>ERG11</i> overexpression in one isolate and only <i>CDR1</i> overexpression in the other isolate may mediate POS-resistance. S663P mutation in <i>FKS2</i> and up-regulation of <i>FKS2</i> may contribute to echinocandin-resistance in both isolates. |
| first_indexed | 2024-03-10T06:46:40Z |
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| language | English |
| last_indexed | 2024-03-10T06:46:40Z |
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| spelling | doaj.art-c995c4f8e7544ce1b04b65a142bc4c202023-11-22T17:13:55ZengMDPI AGAntibiotics2079-63822021-10-011010121710.3390/antibiotics10101217Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and EchinocandinsQiqi Wang0Yun Li1Xuan Cai2Ruoyu Li3Bo Zheng4Ence Yang5Tianyu Liang6Xinyu Yang7Zhe Wan8Wei Liu9Department of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, ChinaInstitute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, ChinaInstitute of Clinical Pharmacology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Dermatology and Venerology, Peking University First Hospital, Beijing 100034, China<i>Candida glabrata</i> is one of the most prevalent causative pathogens of invasive candidiasis, and multidrug-resistant strains are emerging. We identified two clinical isolates of <i>C. glabrata</i>, BMU10720 and BMU10722 sequentially isolated from one patient with multidrug-resistance to posaconazole (POS), caspofungin (CAS), micafungin (MCF), and anidulafungin (ANF). Overexpression of <i>ERG11</i> in BMU10720 and <i>CDR1</i> in BMU10722 were detected at basal level. When exposed to POS, <i>CDR1</i> was significantly up-regulated in both isolates compared with susceptible reference strain, while <i>ERG11</i> was up-regulated considerably only in BMU10720. <i>PDR1</i> sequencing revealed that both isolates harbored P76S, P143T, and D243N substitutions, while <i>ERG11</i> was intact. Cdr1 inhibitor FK520 reversed POS-resistance by down-regulating <i>ERG11</i> expression. <i>FKS</i> sequencing revealed that both isolates harbored S663P substitution in <i>FKS2</i>, and four single nucleotide polymorphisms (SNPs) existed in <i>FKS2</i> genes between BMU10720 and BMU10722, while <i>FKS1</i> was intact. Both <i>FKS1</i> and <i>FKS2</i> were up-regulated by CAS in BMU10720 and BMU10722. FK520 down-regulated <i>FKS2</i> 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 <i>C. glabrata</i> isolates in our study was conferred by different mechanisms. <i>CDR1</i> and <i>ERG11</i> overexpression in one isolate and only <i>CDR1</i> overexpression in the other isolate may mediate POS-resistance. S663P mutation in <i>FKS2</i> and up-regulation of <i>FKS2</i> may contribute to echinocandin-resistance in both isolates.https://www.mdpi.com/2079-6382/10/10/1217<i>Candida glabrata</i>multidrug-resistanceechinocandinstriazolesposaconazoleFK520 |
| spellingShingle | Qiqi Wang Yun Li Xuan Cai Ruoyu Li Bo Zheng Ence Yang Tianyu Liang Xinyu Yang Zhe Wan Wei Liu Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins Antibiotics <i>Candida glabrata</i> multidrug-resistance echinocandins triazoles posaconazole FK520 |
| title | Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins |
| title_full | Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins |
| title_fullStr | Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins |
| title_full_unstemmed | Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins |
| title_short | Two Sequential Clinical Isolates of <i>Candida glabrata</i> with Multidrug-Resistance to Posaconazole and Echinocandins |
| title_sort | two sequential clinical isolates of i candida glabrata i with multidrug resistance to posaconazole and echinocandins |
| topic | <i>Candida glabrata</i> multidrug-resistance echinocandins triazoles posaconazole FK520 |
| url | https://www.mdpi.com/2079-6382/10/10/1217 |
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