Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies.
Candida albicans, an opportunistic fungal pathogen, is a significant cause of human infections, particularly in immunocompromised individuals. Phenotypic plasticity between two morphological phenotypes, yeast and hyphae, is a key mechanism by which C. albicans can thrive in many microenvironments an...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1008690 |
| _version_ | 1819133391635742720 |
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| author | David J Wooten Jorge Gómez Tejeda Zañudo David Murrugarra Austin M Perry Anna Dongari-Bagtzoglou Reinhard Laubenbacher Clarissa J Nobile Réka Albert |
| author_facet | David J Wooten Jorge Gómez Tejeda Zañudo David Murrugarra Austin M Perry Anna Dongari-Bagtzoglou Reinhard Laubenbacher Clarissa J Nobile Réka Albert |
| author_sort | David J Wooten |
| collection | DOAJ |
| description | Candida albicans, an opportunistic fungal pathogen, is a significant cause of human infections, particularly in immunocompromised individuals. Phenotypic plasticity between two morphological phenotypes, yeast and hyphae, is a key mechanism by which C. albicans can thrive in many microenvironments and cause disease in the host. Understanding the decision points and key driver genes controlling this important transition and how these genes respond to different environmental signals is critical to understanding how C. albicans causes infections in the host. Here we build and analyze a Boolean dynamical model of the C. albicans yeast to hyphal transition, integrating multiple environmental factors and regulatory mechanisms. We validate the model by a systematic comparison to prior experiments, which led to agreement in 17 out of 22 cases. The discrepancies motivate alternative hypotheses that are testable by follow-up experiments. Analysis of this model revealed two time-constrained windows of opportunity that must be met for the complete transition from the yeast to hyphal phenotype, as well as control strategies that can robustly prevent this transition. We experimentally validate two of these control predictions in C. albicans strains lacking the transcription factor UME6 and the histone deacetylase HDA1, respectively. This model will serve as a strong base from which to develop a systems biology understanding of C. albicans morphogenesis. |
| first_indexed | 2024-12-22T09:46:33Z |
| format | Article |
| id | doaj.art-893d94a7b6f5436ba2029f38dfd2ca27 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-22T09:46:33Z |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-893d94a7b6f5436ba2029f38dfd2ca272022-12-21T18:30:31ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-03-01173e100869010.1371/journal.pcbi.1008690Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies.David J WootenJorge Gómez Tejeda ZañudoDavid MurrugarraAustin M PerryAnna Dongari-BagtzoglouReinhard LaubenbacherClarissa J NobileRéka AlbertCandida albicans, an opportunistic fungal pathogen, is a significant cause of human infections, particularly in immunocompromised individuals. Phenotypic plasticity between two morphological phenotypes, yeast and hyphae, is a key mechanism by which C. albicans can thrive in many microenvironments and cause disease in the host. Understanding the decision points and key driver genes controlling this important transition and how these genes respond to different environmental signals is critical to understanding how C. albicans causes infections in the host. Here we build and analyze a Boolean dynamical model of the C. albicans yeast to hyphal transition, integrating multiple environmental factors and regulatory mechanisms. We validate the model by a systematic comparison to prior experiments, which led to agreement in 17 out of 22 cases. The discrepancies motivate alternative hypotheses that are testable by follow-up experiments. Analysis of this model revealed two time-constrained windows of opportunity that must be met for the complete transition from the yeast to hyphal phenotype, as well as control strategies that can robustly prevent this transition. We experimentally validate two of these control predictions in C. albicans strains lacking the transcription factor UME6 and the histone deacetylase HDA1, respectively. This model will serve as a strong base from which to develop a systems biology understanding of C. albicans morphogenesis.https://doi.org/10.1371/journal.pcbi.1008690 |
| spellingShingle | David J Wooten Jorge Gómez Tejeda Zañudo David Murrugarra Austin M Perry Anna Dongari-Bagtzoglou Reinhard Laubenbacher Clarissa J Nobile Réka Albert Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. PLoS Computational Biology |
| title | Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. |
| title_full | Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. |
| title_fullStr | Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. |
| title_full_unstemmed | Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. |
| title_short | Mathematical modeling of the Candida albicans yeast to hyphal transition reveals novel control strategies. |
| title_sort | mathematical modeling of the candida albicans yeast to hyphal transition reveals novel control strategies |
| url | https://doi.org/10.1371/journal.pcbi.1008690 |
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