Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content>
ABSTRACT Candida albicans is an important human pathogen responsible for causing both superficial and systemic infections. Its ability to switch from the yeast form to the hyphal growth form is required for its pathogenicity. Acidic pH inhibits hyphal initiation, but the nature of the mechanism for...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-02-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00672-19 |
| _version_ | 1818836624373448704 |
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| author | Ohimai Unoje Mengli Yang Yang Lu Chang Su Haoping Liu |
| author_facet | Ohimai Unoje Mengli Yang Yang Lu Chang Su Haoping Liu |
| author_sort | Ohimai Unoje |
| collection | DOAJ |
| description | ABSTRACT Candida albicans is an important human pathogen responsible for causing both superficial and systemic infections. Its ability to switch from the yeast form to the hyphal growth form is required for its pathogenicity. Acidic pH inhibits hyphal initiation, but the nature of the mechanism for this inhibition is not completely clear. We show that acidic pH represses hyphal initiation independently of the temperature- and farnesol-mediated Nrg1 downregulation. Using a collection of transcription factor deletion mutants, we observed that the sfl1 mutant induced hyphae in acidic pH but not in farnesol at 37°C. Furthermore, transcription of hyphal regulators BRG1 and UME6 was not induced in wild-type (WT) cells but was induced in the sfl1 mutant during hyphal induction in acidic pH. Using the same screening conditions with the collection of kinase mutants, we found that deletions of the core stress response mitogen-activated protein (MAP) kinase HOG1 and its kinase PBS2, the cell wall stress MAP kinase MKC1, and the calcium/calmodulin-dependent kinase CMK1 allowed hyphal initiation in acidic pH. Furthermore, Hog1 phosphorylation induced by high osmotic stress also retarded hyphal initiation, and the effect was abolished in the sfl1 and three kinase mutants but was enhanced in the phosphatase mutant ptp2 ptp3. We also found functional associations among Cmk1, Hog1, and Sfl1 for cation stress. Our study results suggest that robust hyphal initiation requires downregulation of both Nrg1 and Sfl1 transcriptional repressors as well as timely BRG1 expression. Acidic pH and cationic stress retard hyphal initiation via the stress-responsive kinases and Sfl1. IMPORTANCE Candida albicans is a commensal as well as a pathogen of humans. C. albicans is able to mount a cellular response to a diverse range of external stimuli in the host and switch reversibly between the yeast and hyphal growth forms. Hyphal development is a key virulence determinant. Here, we studied how C. albicans senses different environmental signals to control its growth forms. Our study results suggest that robust hyphal development requires downregulation of two transcriptional repressors, Nrg1 and Sfl1. Acidic pH or cationic stress inhibits hyphal formation via stress-responsive kinases and Sfl1. |
| first_indexed | 2024-12-19T03:09:34Z |
| format | Article |
| id | doaj.art-4c036279cbde44d3a7b6570befdaa1c4 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T03:09:34Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-4c036279cbde44d3a7b6570befdaa1c42022-12-21T20:38:03ZengAmerican Society for MicrobiologymSphere2379-50422020-02-015110.1128/mSphere.00672-19Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content>Ohimai Unoje0Mengli Yang1Yang Lu2Chang Su3Haoping Liu4Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USADepartment of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USADepartment of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USADepartment of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USADepartment of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, California, USAABSTRACT Candida albicans is an important human pathogen responsible for causing both superficial and systemic infections. Its ability to switch from the yeast form to the hyphal growth form is required for its pathogenicity. Acidic pH inhibits hyphal initiation, but the nature of the mechanism for this inhibition is not completely clear. We show that acidic pH represses hyphal initiation independently of the temperature- and farnesol-mediated Nrg1 downregulation. Using a collection of transcription factor deletion mutants, we observed that the sfl1 mutant induced hyphae in acidic pH but not in farnesol at 37°C. Furthermore, transcription of hyphal regulators BRG1 and UME6 was not induced in wild-type (WT) cells but was induced in the sfl1 mutant during hyphal induction in acidic pH. Using the same screening conditions with the collection of kinase mutants, we found that deletions of the core stress response mitogen-activated protein (MAP) kinase HOG1 and its kinase PBS2, the cell wall stress MAP kinase MKC1, and the calcium/calmodulin-dependent kinase CMK1 allowed hyphal initiation in acidic pH. Furthermore, Hog1 phosphorylation induced by high osmotic stress also retarded hyphal initiation, and the effect was abolished in the sfl1 and three kinase mutants but was enhanced in the phosphatase mutant ptp2 ptp3. We also found functional associations among Cmk1, Hog1, and Sfl1 for cation stress. Our study results suggest that robust hyphal initiation requires downregulation of both Nrg1 and Sfl1 transcriptional repressors as well as timely BRG1 expression. Acidic pH and cationic stress retard hyphal initiation via the stress-responsive kinases and Sfl1. IMPORTANCE Candida albicans is a commensal as well as a pathogen of humans. C. albicans is able to mount a cellular response to a diverse range of external stimuli in the host and switch reversibly between the yeast and hyphal growth forms. Hyphal development is a key virulence determinant. Here, we studied how C. albicans senses different environmental signals to control its growth forms. Our study results suggest that robust hyphal development requires downregulation of two transcriptional repressors, Nrg1 and Sfl1. Acidic pH or cationic stress inhibits hyphal formation via stress-responsive kinases and Sfl1.https://journals.asm.org/doi/10.1128/mSphere.00672-19Candida albicanshyphal formationSfl1 |
| spellingShingle | Ohimai Unoje Mengli Yang Yang Lu Chang Su Haoping Liu Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> mSphere Candida albicans hyphal formation Sfl1 |
| title | Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_full | Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_fullStr | Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_full_unstemmed | Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_short | Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in <named-content content-type="genus-species">Candida albicans</named-content> |
| title_sort | linking sfl1 regulation of hyphal development to stress response kinases in named content content type genus species candida albicans named content |
| topic | Candida albicans hyphal formation Sfl1 |
| url | https://journals.asm.org/doi/10.1128/mSphere.00672-19 |
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