Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling
Infections by the major opportunistic pathogen of human <i>Candida albicans</i> are commonly treated with echinocandin (ECN) drugs. However, <i>C. albicans</i> can adapt to grow in the presence of certain amounts of ECNs. Prior studies by several laboratories have defined mul...
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2025-02-01
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| author | Sudisht K. Sah Anshuman Yadav Tyler Stahl Jeffrey J. Hayes Michael Bulger Elena Rustchenko |
| author_facet | Sudisht K. Sah Anshuman Yadav Tyler Stahl Jeffrey J. Hayes Michael Bulger Elena Rustchenko |
| author_sort | Sudisht K. Sah |
| collection | DOAJ |
| description | Infections by the major opportunistic pathogen of human <i>Candida albicans</i> are commonly treated with echinocandin (ECN) drugs. However, <i>C. albicans</i> can adapt to grow in the presence of certain amounts of ECNs. Prior studies by several laboratories have defined multiple genes, as well as mechanisms involving induced aneuploidy, that can govern this. Still, the mechanisms of ECN adaptation are not fully understood. Here, we use genome-wide profiling of chromatin accessibility by ATAC-seq to determine if ECN adaptation is reflected in changes in the chromatin landscape in the absence of aneuploidy. We find that drug adaptation is coupled with multiple changes in chromatin accessibility genome-wide, which occur predominantly in gene promoter regions. Areas of increased accessibilities in promoters are enriched with the binding motifs for at least two types of transcription factors: zinc finger and basic leucine zipper. We also find that chromatin changes are often associated with differentially expressed genes including genes with functions relevant to the ECN-adapted phenotype, such as cell wall biosynthesis. Consistent with this, we find that the cell wall is remodeled in ECN-adapted mutants, with chitin up and glucan down and increased cell surface exposure. A full understanding of ECN adaptation processes is of critical importance for the prevention of clinical resistance. |
| format | Article |
| id | doaj-art-75227be47810482d95cac0a438d2dea1 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-02-01 |
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| series | Journal of Fungi |
| spelling | doaj-art-75227be47810482d95cac0a438d2dea12025-08-20T02:04:01ZengMDPI AGJournal of Fungi2309-608X2025-02-0111211010.3390/jof11020110Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall RemodelingSudisht K. Sah0Anshuman Yadav1Tyler Stahl2Jeffrey J. Hayes3Michael Bulger4Elena Rustchenko5Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USAGenomic Research Center, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USACenter for Pediatric Biochemical Research, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USADepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USAInfections by the major opportunistic pathogen of human <i>Candida albicans</i> are commonly treated with echinocandin (ECN) drugs. However, <i>C. albicans</i> can adapt to grow in the presence of certain amounts of ECNs. Prior studies by several laboratories have defined multiple genes, as well as mechanisms involving induced aneuploidy, that can govern this. Still, the mechanisms of ECN adaptation are not fully understood. Here, we use genome-wide profiling of chromatin accessibility by ATAC-seq to determine if ECN adaptation is reflected in changes in the chromatin landscape in the absence of aneuploidy. We find that drug adaptation is coupled with multiple changes in chromatin accessibility genome-wide, which occur predominantly in gene promoter regions. Areas of increased accessibilities in promoters are enriched with the binding motifs for at least two types of transcription factors: zinc finger and basic leucine zipper. We also find that chromatin changes are often associated with differentially expressed genes including genes with functions relevant to the ECN-adapted phenotype, such as cell wall biosynthesis. Consistent with this, we find that the cell wall is remodeled in ECN-adapted mutants, with chitin up and glucan down and increased cell surface exposure. A full understanding of ECN adaptation processes is of critical importance for the prevention of clinical resistance.https://www.mdpi.com/2309-608X/11/2/110<i>Candida albicans</i>ATAC-seqechinocandin adaptation |
| spellingShingle | Sudisht K. Sah Anshuman Yadav Tyler Stahl Jeffrey J. Hayes Michael Bulger Elena Rustchenko Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling Journal of Fungi <i>Candida albicans</i> ATAC-seq echinocandin adaptation |
| title | Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling |
| title_full | Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling |
| title_fullStr | Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling |
| title_full_unstemmed | Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling |
| title_short | Echinocandin Adaptation in <i>Candida albicans</i> Is Accompanied by Altered Chromatin Accessibility at Gene Promoters and by Cell Wall Remodeling |
| title_sort | echinocandin adaptation in i candida albicans i is accompanied by altered chromatin accessibility at gene promoters and by cell wall remodeling |
| topic | <i>Candida albicans</i> ATAC-seq echinocandin adaptation |
| url | https://www.mdpi.com/2309-608X/11/2/110 |
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