Systematic gene overexpression in Candida albicans identifies a regulator of early adaptation to the mammalian gut

Cellular Microbiology
Sadri ZnaidiChristophe d'Enfert

Abstract

Candida albicans is part of the human gastrointestinal (GI) microbiota. To better understand how C. albicans efficiently establishes GI colonisation, we competitively challenged growth of 572 signature-tagged strains (~10% genome coverage), each conditionally overexpressing a single gene, in the murine gut. We identified CRZ2, a transcription factor whose overexpression and deletion respectively increased and decreased early GI colonisation. Using clues from genome-wide expression and gene-set enrichment analyses, we found that the optimal activity of Crz2p occurs under hypoxia at 37°C, as evidenced by both phenotypic and transcriptomic analyses following CRZ2 genetic perturbation. Consistent with early colonisation of the GI tract, we show that CRZ2 overexpression confers resistance to acidic pH and bile salts, suggesting an adaptation to the upper sections of the gut. Genome-wide location analyses revealed that Crz2p directly modulates the expression of many mannosyltransferase- and cell-wall protein-encoding genes, suggesting a link with cell-wall function. We show that CRZ2 overexpression alters cell-wall phosphomannan abundance and increases sensitivity to tunicamycin, suggesting a role in protein glycosylation. Our study ...Continue Reading

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Citations

Jun 26, 2020·Frontiers in Microbiology·Tibor NemethAttila Gacser
May 28, 2019·F1000Research·Robert A Arkowitz, Martine Bassilana
Dec 3, 2020·Frontiers in Microbiology·Eric DelarzeDominique Sanglard
Dec 6, 2020·Nature Communications·Arturo Hernández-CervantesChristophe d'Enfert
Jun 3, 2020·Current Opinion in Microbiology·Andrea Hodgins-Davis, Teresa R O'Meara
Sep 28, 2021·Molecular Microbiology·Laxmi Shanker RaiSophie Bachellier-Bassi
Dec 6, 2021·FEMS Yeast Research·Nicholas C GervaisRebecca S Shapiro

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Datasets Mentioned

BETA
AFC60678.1
GPL17420
GSE67226
GPL13696
GSE67233

Methods Mentioned

BETA
PCR
flow cytometry
immunoprecipitation
tandem affinity purification
tandem
glycosylation

Software Mentioned

Cytoscape EnrichmentMap
Excel
Extract Genomic DNA
ArrayPipe
GenePix
GSEA
GSEA PreRanked
GenePix Pro
Cytoscape GSEA
Integrated Genomics Viewer

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