Transcript profiling in <i>Candida albicans</i> reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1

Murad, Abdul Munir Abd.; d’Enfert, Christophe; Gaillardin, Claude; Tournu, Hélène; Tekaia, Fredj; Talibi, Driss; Maréchal, Daniel; Marchais, Véronique; Cottin, Jane; Brown, Alistair J. P.

doi:10.1046/j.1365-2958.2001.02713.x

Cited by 199 publications

(212 citation statements)

References 68 publications

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“…In C. albicans, expression of GAL1, GAL7, and GAL10 is likely regulated by Cph1p and Mig1p (28,36,37). Using a DNA binding motif prediction algorithm (Materials and Methods), we found a 10-bp motif that resembles a C. albicans Cph1p binding site upstream of the clustered S. pombe GAL10 (Fig.…”

Section: Gal Gene Cluster In Schizosaccharomyces Originated By Hgt Frommentioning

confidence: 96%

Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi

Slot

Rokas

2010

Proc. Natl. Acad. Sci. U.S.A.

150

158

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A notable characteristic of fungal genomes is that genes involved in successive steps of a metabolic pathway are often physically linked or clustered. To investigate how such clusters of functionally related genes are assembled and maintained, we examined the evolution of gene sequences and order in the galactose utilization (GAL) pathway in whole-genome data from 80 diverse fungi. We found that GAL gene clusters originated independently and by different mechanisms in three unrelated yeast lineages. Specifically, the GAL cluster found in Saccharomyces and Candida yeasts originated through the relocation of native unclustered genes, whereas the GAL cluster of Schizosaccharomyces yeasts was acquired through horizontal gene transfer from a Candida yeast. In contrast, the GAL cluster of Cryptococcus yeasts was assembled independently from the Saccharomyces/Candida and Schizosaccharomyces GAL clusters and coexists in the Cryptococcus genome with unclustered GAL paralogs. These independently evolved GAL clusters represent a striking example of analogy at the genomic level. We also found that species with GAL clusters exhibited significantly higher rates of GAL pathway loss than species with unclustered GAL genes. These results suggest that clustering of metabolic genes might facilitate fungal adaptation to changing environments both through the acquisition and loss of metabolic capacities. F ungal genes involved in successive steps of a pathway are frequently physically clustered (1-12). Evolutionary analysis of several different fungal gene clusters has shown that they have originated through different mechanisms (13-16). For example, the DAL cluster for allantoin utilization in Saccharomyces cerevisiae and close relatives originated through adaptive gene relocation (13), whereas a nitrate assimilation cluster in Trichoderma originated through horizontal gene transfer (14). However, it is unclear how these mechanisms shape the assembly of gene clusters, or how the evolutionary trajectories differ between species containing clusters and species in which the genes in a pathway are scattered across the genome.To better understand the origins and maintenance of gene clusters over a large evolutionary timescale and a range of ecological conditions, we investigated the evolution of the Leloir galactose utilization (GAL) pathway in fungi. The detailed knowledge on GAL pathway function in S. cerevisiae (15, 16), and the abundance of genomic data from a wide diversity of fungal species (17), make it an excellent model pathway to address these questions. Furthermore, the relative galactose content varies substantially among different plant substrata (from hundreds of mg/g legume seeds and algal mats to less than 1 mg/g in some fruits) (18-21), suggesting that the natural substrates of fungi have likely provided ample opportunity for populations to evolve niche-dependent adaptations for galactose utilization.The protein products of three GAL genes (GAL1, GAL7, and GAL10) are involved in four enzymatic steps (22). In the first s...

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Section: Gal Gene Cluster In Schizosaccharomyces Originated By Hgt Frommentioning

confidence: 96%

Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi

Slot

Rokas

2010

Proc. Natl. Acad. Sci. U.S.A.

150

158

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“…IHD1, identified in a genome-wide transcriptional profiling of genes induced or repressed during hyphal development by Nantel et al (2002), was also found in this cluster, and further confirmed by Northern analysis ( Figure 5B). The gene was independently found by Murad et al (2001) as one of the genes regulated by the Nrg1 and Tup1 repressors. IHD1 is predicted to encode a GPI-anchored cell wall protein (De Groot et al, 2003), and the protein sequence also has similarity to glucan 1,4-␣-glucosidase Sta1 in Saccharomyces diastaticus (Yamashita et al, 1985).…”

Section: Flo8 Is Required For Expressing Subsets Of Efg1-regulated Genesmentioning

confidence: 99%

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

Cao

Lane

Raniga

et al. 2006

MBoC

198

255

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The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene expression. The flo8/flo8 mutant is avirulent in a mouse model of systemic infection. Genome-wide transcription profiling of efg1/efg1 and flo8/flo8 using a C. albicans DNA microarray suggests that Flo8 controls subsets of Efg1-regulated genes. Most of these genes are hypha specific, including HGC1 and IHD1. We also show that Flo8 interacts with Efg1 in yeast and hyphal cells by in vivo immunoprecipitation. Similar to efg1/efg1, flo8/flo8 and cdc35/cdc35 show enhanced hyphal growth under an embedded growth condition. Our results suggest that Flo8 may function downstream of the cAMP/PKA pathway, and together with Efg1, regulates the expression of hypha-specific genes and genes that are important for the virulence of C. albicans.

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“…Under yeast favouring conditions, the expression of hyphae-specific genes is controlled by a set of transcriptional repressors (Murad et al, 2001a(Murad et al, , 2001b. The cAMP-protein kinase A-pathway plays a central role in the induction of hyphae: the adenylate cyclase Cyr1p is activated by a number of stimuli, such as CO 2 -concentration, and signals from other proteins, e.g.…”

Section: Introductionmentioning

confidence: 99%

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

Heintz‐Buschart¹,

Eickhoff²,

Hohn³

et al. 2013

Journal of Biotechnology

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Candida albicans is one of the most common opportunistic fungal pathogens, causing lifethreatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast-hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model.We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promotor activity of the hyphae-specific HWP1 to β-

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Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1

Cited by 199 publications

References 68 publications

Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi

Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi

The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

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