Lineage-specific selection and the evolution of virulence in Candida albicans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA706031 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13833813.fastq.gz | Fastqsanger.gz | |||
| SRR13833814.fastq.gz | Fastqsanger.gz | |||
| SRR13833815.fastq.gz | Fastqsanger.gz | |||
| SRR13833816.fastq.gz | Fastqsanger.gz | |||
| SRR13833817.fastq.gz | Fastqsanger.gz |
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Project description:Project Abstract : Paf1C is a general transcription regulator and is associated with various human diseases. One of its subunits, CTR9, is known as a structurally and functionally core component of Paf1C. While its role in higher eukaryotes have been researched, the association between the core component and human fungal pathogen is not fully understood yet. During pre-infection process, Candida albicans adheres to the surface of hosts and sufficiently grows as the circular form. Under immune deficiency condition, C. albicans enters into the infection process and forms hyphae. Here, we performed virulence tests and transcriptome analysis to identify the role of CTR9 in two infection stages. In pre-infection process, CTR9 regulates basic cellular processes and metabolism, affecting cell growth. Of metabolic processes, methionine biosynthetic genes are significantly dependent on CTR9. This pathway hardly affects cell abundance for pre-infection stage, but has considerable effect on hyphal formation during infection stage. Therefore, it shows that methionine biosynthetic pathway mediated by CTR9 is essential for pathogenesis of C. albicans.
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Project description:Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. ΔΔsfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the ΔΔsfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, ΔΔsfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.
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Project description:The opportunistic human pathogens, Candida albicans and Candida dubliniensis, are closely related species displaying large differences in virulence, but the reasons for these differences are elusive. Microarray-based comparative analysis of global gene expression in the two species incubated on reconstituted human oral epithelium (RHE) was used to identify specific and common changes in gene expression and find novel C. albicans virulence genes Comparative analysis of global gene expression in Candida albicans SC5314 and Candida dubliniensis CD36 in reconstituted human oral epithelium (RHE), polycarbonate filter (PCF; used as RHE support matrix) 30 and 90 min postinoculation, and in cultures used as inocula (0 min). Gene expression in C. albicans and C. dubliniensis was assessed by co-hybridizations matched by treatments. Performed in two or three biological replicates with reciprocal dye swaps for each biological replicate. Gene expression of Candida cells on RHE was normalized to gene expression in reference control (PCF); log2 ratios were calculated by dividing spot intensity of experimental (C. albicans) by that of the reference control (C. dubliniensis).
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