The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i>
The endocytic and secretory pathways of the fungal pathogen <i>Candida albicans</i> are fundamental to various key cellular processes such as cell growth, cell wall integrity, protein secretion, hyphal formation, and pathogenesis. Our previous studies focused on several candidate genes i...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/11/1097 |
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| author | Miranda Yu Dakota Ma Susan Eszterhas Christiane Rollenhagen Samuel A. Lee |
| author_facet | Miranda Yu Dakota Ma Susan Eszterhas Christiane Rollenhagen Samuel A. Lee |
| author_sort | Miranda Yu |
| collection | DOAJ |
| description | The endocytic and secretory pathways of the fungal pathogen <i>Candida albicans</i> are fundamental to various key cellular processes such as cell growth, cell wall integrity, protein secretion, hyphal formation, and pathogenesis. Our previous studies focused on several candidate genes involved in early endocytosis, including <i>ENT2</i> and <i>END3</i>, that play crucial roles in such processes. However, much remains to be discovered about other endocytosis-related genes and their contributions toward <i>Candida albicans</i> secretion and virulence. In this study, we examined the functions of the early endocytosis gene <i>PAL1</i> using a reverse genetics approach based on CRISPR-Cas9-mediated gene deletion. <i>Saccharomyces cerevisiae</i> Pal1 is a protein in the early coat complex involved in clathrin-mediated endocytosis that is later internalized with the coat. The <i>C. albicans pal1</i>Δ/Δ null mutant demonstrated increased resistance to the antifungal agent caspofungin and the cell wall stressor Congo Red. In contrast, the null mutant was more sensitive to the antifungal drug fluconazole and low concentrations of SDS than the wild type (WT) and the re-integrant (KI). While <i>pal1</i>Δ/Δ can form hyphae and a biofilm, under some hyphal-inducing conditions, it was less able to demonstrate filamentous growth when compared to the WT and KI. The <i>pal1</i>Δ/Δ null mutant had no defect in clathrin-mediated endocytosis, and there were no changes in virulence-related processes compared to controls. Our results suggest that <i>PAL1</i> has a role in susceptibility to antifungal agents, cell wall integrity, and membrane stability related to early endocytosis. |
| first_indexed | 2024-03-09T16:41:50Z |
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| last_indexed | 2024-03-09T16:41:50Z |
| publishDate | 2023-11-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-2df6eb0e2cd242a4943735e835827b852023-11-24T14:51:08ZengMDPI AGJournal of Fungi2309-608X2023-11-01911109710.3390/jof9111097The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i>Miranda Yu0Dakota Ma1Susan Eszterhas2Christiane Rollenhagen3Samuel A. Lee4Thayer School of Engineering at Dartmouth, Dartmouth College, Hanover, NH 03755, USAMedicine Service, White River Junction VA Medical Center, Hartford, VT 05009, USAMedicine Service, White River Junction VA Medical Center, Hartford, VT 05009, USADepartment of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USADepartment of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USAThe endocytic and secretory pathways of the fungal pathogen <i>Candida albicans</i> are fundamental to various key cellular processes such as cell growth, cell wall integrity, protein secretion, hyphal formation, and pathogenesis. Our previous studies focused on several candidate genes involved in early endocytosis, including <i>ENT2</i> and <i>END3</i>, that play crucial roles in such processes. However, much remains to be discovered about other endocytosis-related genes and their contributions toward <i>Candida albicans</i> secretion and virulence. In this study, we examined the functions of the early endocytosis gene <i>PAL1</i> using a reverse genetics approach based on CRISPR-Cas9-mediated gene deletion. <i>Saccharomyces cerevisiae</i> Pal1 is a protein in the early coat complex involved in clathrin-mediated endocytosis that is later internalized with the coat. The <i>C. albicans pal1</i>Δ/Δ null mutant demonstrated increased resistance to the antifungal agent caspofungin and the cell wall stressor Congo Red. In contrast, the null mutant was more sensitive to the antifungal drug fluconazole and low concentrations of SDS than the wild type (WT) and the re-integrant (KI). While <i>pal1</i>Δ/Δ can form hyphae and a biofilm, under some hyphal-inducing conditions, it was less able to demonstrate filamentous growth when compared to the WT and KI. The <i>pal1</i>Δ/Δ null mutant had no defect in clathrin-mediated endocytosis, and there were no changes in virulence-related processes compared to controls. Our results suggest that <i>PAL1</i> has a role in susceptibility to antifungal agents, cell wall integrity, and membrane stability related to early endocytosis.https://www.mdpi.com/2309-608X/9/11/1097<i>Candida albicans</i>clathrin-mediated endocytosisstress tolerancehyphal formation |
| spellingShingle | Miranda Yu Dakota Ma Susan Eszterhas Christiane Rollenhagen Samuel A. Lee The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> Journal of Fungi <i>Candida albicans</i> clathrin-mediated endocytosis stress tolerance hyphal formation |
| title | The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> |
| title_full | The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> |
| title_fullStr | The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> |
| title_full_unstemmed | The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> |
| title_short | The Early Endocytosis Gene <i>PAL1</i> Contributes to Stress Tolerance and Hyphal Formation in <i>Candida albicans</i> |
| title_sort | early endocytosis gene i pal1 i contributes to stress tolerance and hyphal formation in i candida albicans i |
| topic | <i>Candida albicans</i> clathrin-mediated endocytosis stress tolerance hyphal formation |
| url | https://www.mdpi.com/2309-608X/9/11/1097 |
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