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| Status |
Public on Sep 19, 2019 |
| Title |
A novel genetic circuitry governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida albicans |
| Organism |
Candida albicans |
| Experiment type |
Expression profiling by array
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| Summary |
Inside the human host, the pathogenic yeast Candida albicans colonizes predominantly oxygen-poor niches such as the gastrointestinal and vaginal tracts, but also oxygen-rich environments such as cutaneous epithelial cells and oral mucosa. This suppleness requires an effective mechanism to reprogram reversibly the primary metabolism in response to oxygen variation. Here, we have uncovered that Snf5, a subunit of SWI/SNF chromatin remodeling complex, is a major transcriptional regulator that links oxygen status to the metabolic capacity of C. albicans. Snf5 and other subunits of SWI/SNF complex were required to activate genes of carbon utilization and other carbohydrates related process specifically under hypoxia. snf5 mutant exhibited an altered metabolome reflecting that SWI/SNF plays an essential role in maintaining metabolic homeostasis and carbon flux in C. albicans under hypoxia. Snf5 was necessary to activate the transcriptional program linked to both commensal and invasive growth. Accordingly, snf5 was unable to maintain its growth in the stomach, the cecum and the colon of mice. snf5 was also avirulent as it was unable to invade Galleria larvae or to cause damage to human enterocytes and murine macrophages. Among candidates of signaling pathways in which Snf5 might operate, phenotypic analysis revealed that mutants of Ras1-cAMP-PKA pathway, as well as mutants of Yak1 and Yck2 kinases exhibited a similar carbon flexibility phenotype as did snf5 under hypoxia. Genetic interaction analysis indicated that the adenylate cyclase Cyr1, a key component of the Ras1-cAMP pathway genetically with Snf5. Our study yielded new insight into the oxygen-sensitive regulatory circuit that control metabolic flexibility, stress, commensalism and virulence in C. albicans.
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| Overall design |
To investigate the role of the SWI/SNF subunit, Snf5, in metabolic flexibility under hypoxia in C. albicans, we performed genome-wide transcriptional profiling by microarray. Both WT (SN250) and snf5 mutant cells were grown on YP-Sucrose under both hypoxia and normoxia and their transcriptomes were characterized.
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| Contributor(s) |
Burgain A, Pic É, Markey L, Tebbji F, Kumamoto CA, Sellam A |
| Citation(s) |
31809527 |
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| Submission date |
Sep 18, 2019 |
| Last update date |
Dec 19, 2019 |
| Contact name |
Adnane Sellam |
| E-mail(s) |
adnane.sellam@gmail.com
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| Organization name |
University Laval
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| Street address |
2705 Laurier Blvd.
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| City |
Quebec city |
| ZIP/Postal code |
G1V 4G2 |
| Country |
Canada |
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| Platforms (1) |
| GPL9818 |
NRC-BRI C. albicans expression microarray V2.0 |
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| Samples (4)
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| GSM4083834 |
WT-Hypoxia vs WT-Normoxia - Replicat 1 |
| GSM4083835 |
WT-Hypoxia vs WT-Normoxia - Replicat 2 |
| GSM4083836 |
snf5-Hypoxia vs snf5-Normoxia - Replicat 1 |
| GSM4083837 |
snf5-Hypoxia vs snf5-Normoxia - Replicat 2 |
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| Relations |
| BioProject |
PRJNA566155 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137655_RAW.tar |
5.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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