Glucose Sensing Network in
            <i>Candida albicans</i>
            : a Sweet Spot for Fungal Morphogenesis

Sabina, Jeffrey; Brown, Victoria E.

doi:10.1128/ec.00138-09

Cited by 74 publications

(77 citation statements)

References 108 publications

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“…2; see also the supplemental material). Some of these genes may also have been derepressed by a shift out of glucose medium rather than induced by GlcNAc (27). To help distinguish between these The genes induced most consistently and to the highest levels; (center) genes encoding proteins that synthesize GlcNAc and chitin synthase genes, which show essentially no change in expression; (bottom) the most highly repressed genes.…”

Section: Resultsmentioning

confidence: 99%

Identification of GIG1 , a GlcNAc-Induced Gene in Candida albicans Needed for Normal Sensitivity to the Chitin Synthase Inhibitor Nikkomycin Z

et al. 2010

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The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria to humans, but its roles in cell signaling are less well understood. GlcNAc induces two pathways in the human fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling, which stimulates the formation of hyphal cells and the expression of virulence genes, and the other pathway induces genes needed to catabolize GlcNAc. Microarray analysis of gene expression was carried out under four different conditions in order to characterize the transcriptional changes induced by GlcNAc. The most highly induced genes include those that encode a GlcNAc transporter (NGT1) and the GlcNAc catabolic enzymes (HXK1, DAC1, and NAG1). GlcNAc also activated most of the genes whose expression is increased when cells are triggered with other stimuli to form hyphae. Surprisingly, GlcNAc also induced a subset of genes that are regulated by galactose (GAL1, GAL7, and GAL10), which may be due to cross talk between signaling pathways. A novel GlcNAc-induced gene, GIG1, which is not essential for GlcNAc catabolism or the induction of hyphae, was identified. However, a Gig1-green fluorescent protein (GFP) fusion protein was specifically induced by GlcNAc, and not by other sugars. Gig1-GFP localized to the cytoplasm, where GlcNAc metabolism occurs. Significantly, a gig1⌬ mutant displayed increased resistance to nikkomycin Z, which inhibits chitin synthase from converting UDP-GlcNAc into cell wall chitin. Gig1 is highly conserved in fungi, especially those that contain GlcNAc catabolic genes. These results implicate Gig1 in GlcNAc metabolism.

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Section: Resultsmentioning

confidence: 99%

Identification of GIG1 , a GlcNAc-Induced Gene in Candida albicans Needed for Normal Sensitivity to the Chitin Synthase Inhibitor Nikkomycin Z

et al. 2010

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“…In S. cerevisiae the transcription factor Gal4 activates the galactose utilization genes GAL1, GAL7, and GAL10, whereas in C. albicans, Gal4 regulates the balance between respiration and fermentation in a carbon-source-dependent fashion (Askew et al 2009). This presumably reflects the importance of galactose as a carbon source for the pathogenic fungus (Sabina and Brown 2009), particularly in lactating mothers and their infants. The glycolytic transcriptional circuit has also undergone significant transcriptional rewiring.…”

Section: Regulatory Rewiring Of Central Carbon Metabolismmentioning

confidence: 99%

Metabolism in Fungal Pathogenesis

Ene¹,

Brunke²,

Brown³

et al. 2014

Cold Spring Harbor Perspectives in Medicine

107

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Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host -fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. N utrient assimilation is a central and fundamental prerequisite for the growth and survival of all living organisms. Pathogenic fungi inhabit dynamic and contrasting niches and must display rapid and effective adaptation to changes in nutrient availability in these microenvironments. To achieve this, they regulate specific nutrient uptake mechanisms and modulate their metabolism, displaying an impressive degree of metabolic flexibility. This metabolic flexibility, which enhances the fitness of the fungus, is often as essential for pathogenicity as virulence factors, thereby representing an attractive target for potential therapeutic intervention.The major fungal pathogens of humans have evolved in a polyphyletic manner (i.e., pathogenicity has emerged independently in different

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“…Recent studies with Candida albicans have shown that many genes upregulated during glucose starvation are also upregulated during galactose starvation (7). In particular, C. albicans senses both sugars through Hgt4, which then leads to phosphorylation of Rgt1, resulting in the transcription of various genes (40). Our results suggest that the pathway leading to App1 upregulation during glucose starvation may be more similar to that in C. albicans than to that in S. cerevisiae, which responds to glucose and galactose through different pathways (5,7).…”

Section: Discussionmentioning

confidence: 99%

Role of Glucose in the Expression of Cryptococcus neoformans Antiphagocytic Protein 1, App1

Williams

Poeta

2011

Eukaryot Cell

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The cryptococcus-specific protein antiphagocytic protein 1 (App1) regulates Cryptococcus neoformans virulence by controlling macrophage-driven fungal phagocytosis. This is accomplished through complement receptors (CR), specifically CR3. When inhaled, C. neoformans can cause a life-threatening meningoencephalitis in immunocompromised patients. Because glucose starvation can significantly change the gene expression and virulence of C. neoformans and because App1 is critical for phagocytosis in the lung-a low-glucose environment-we investigated the role of glucose in App1 expression. We found that App1 was upregulated dramatically under low-glucose conditions, and it was upregulated when C. neoformans cells were incubated in bronchoalveolar lavage (BAL) fluid, serum, and cerebrospinal fluid, which are low-glucose environments. Characterization of App1's regulation based on mammalian lung physiology revealed that App1 is upregulated via both increases in transcription and increases in mRNA stability. Our data provide new insights regarding C. neoformans adaptations to low-glucose environments.

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Glucose Sensing Network in Candida albicans : a Sweet Spot for Fungal Morphogenesis

Cited by 74 publications

References 108 publications

Identification of GIG1 , a GlcNAc-Induced Gene in Candida albicans Needed for Normal Sensitivity to the Chitin Synthase Inhibitor Nikkomycin Z

Identification of GIG1 , a GlcNAc-Induced Gene in Candida albicans Needed for Normal Sensitivity to the Chitin Synthase Inhibitor Nikkomycin Z

Metabolism in Fungal Pathogenesis

Role of Glucose in the Expression of Cryptococcus neoformans Antiphagocytic Protein 1, App1

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