Role of the Vps34p-interacting protein Ade5,7p in hyphal growth and virulence of Candida albicans

Jezewski, Susann; Heide, Monika von der; Poltermann, Sophia; Härtl, Albert; Künkel, W.; Zipfel, Peter F.; Eck, Raimund

doi:10.1099/mic.0.2006/004028-0

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…cerevisiae and C . albicans encoding a bifunctional enzyme possessing aminoimidazole ribotide synthase and glycinamide ribotide synthase activities [ 38 , 39 ]. The similarity is largely confined to the region where the predicted functional domains are located.…”

Section: Resultsmentioning

confidence: 99%

Identification of factors involved in dimorphism and pathogenicity of Zymoseptoria tritici

et al. 2017

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A forward genetics approach was applied in order to investigate the molecular basis of morphological transition in the wheat pathogenic fungus Zymoseptoria tritici. Z. tritici is a dimorphic plant pathogen displaying environmentally regulated morphogenetic transition between yeast-like and hyphal growth. Considering the infection mode of Z. tritici, the switching to hyphal growth is essential for pathogenicity allowing the fungus the host invasion through natural openings like stomata. We exploited a previously developed Agrobacterium tumefaciens-mediated transformation (ATMT) to generate a mutant library by insertional mutagenesis including more than 10,000 random mutants. To identify genes involved in dimorphic switch, a plate-based screening system was established. With this approach eleven dimorphic switch deficient random mutants were recovered, ten of which exhibited a yeast-like mode of growth and one mutant predominantly growing filamentously, producing high amount of mycelium under different incubation conditions. Using genome walking approach previously established, the T-DNA integration sites were recovered and the disrupted genomic loci of corresponding mutants were identified and validated within reverse genetics approach. As prove of concept, two of the random mutants obtained were selected for further investigation using targeted gene inactivation. Both genes deduced were found to encode known factors, previously characterized in other fungi: Ssk1p being constituent of HOG pathway and Ade5,7p involved in de novo purine biosynthesis. The targeted mutant strains defective in these genes exhibit a drastically impaired virulence within infection assays on whole wheat plants. Moreover exploiting further physiological assays the predicted function for both gene products could be confirmed in concordance with conserved biological role of homologous proteins previously described in other fungal organisms.PLOS ONE | https://doi.org/10.1371/journal.pone

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Section: Resultsmentioning

confidence: 99%

Identification of factors involved in dimorphism and pathogenicity of Zymoseptoria tritici

et al. 2017

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“…In C. albicans , grf10 Δ (referred to as pho2 Δ) and bas1 Δ mutants exhibit a leaky adenine auxotrophy, whereas pho4 Δ but not grf10 Δ mutants exhibit a growth defect under phosphate limitation conditions ( 20 ), indicating a divergence of function. Importantly, purine biosynthetic genes have been shown to be involved with virulence in C. albicans ( 21 – 23 ), underlying a critical role of this metabolic pathway in fungal pathogenicity. Although maintenance of purine nucleotide pools is crucial for cell survival and pathogenicity, the genetic regulation of this pathway has not been well characterized in C. albicans .…”

Section: Introductionmentioning

confidence: 99%

Grf10 and Bas1 Regulate Transcription of Adenylate and One-Carbon Biosynthesis Genes and Affect Virulence in the Human Fungal Pathogen Candida albicans

Wangsanut

Ghosh

Metzger

et al. 2017

mSphere

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Candida albicans is a commensal and a common constituent of the human microbiota; however, it can become pathogenic and cause infections in both immunocompetent and immunocompromised people. C. albicans exhibits remarkable metabolic versatility as it can colonize multiple body sites as a commensal or pathogen. Understanding how C. albicans adapts metabolically to each ecological niche is essential for developing novel therapeutic approaches. Purine metabolism has been targeted pharmaceutically in several diseases; however, the regulation of this pathway has not been fully elucidated in C. albicans. Here, we report how C. albicans controls the AMP de novo biosynthesis pathway in response to purine availability. We show that the lack of the transcription factors Grf10 and Bas1 leads to purine metabolic dysfunction, and this dysfunction affects the ability of C. albicans to establish infections.

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“…We have expanded the understanding of Grf10-dependent target genes to multiple pathways: purine biosynthesis and uptake, yeast to hyphae switching, copper and iron response, and uptake of inorganic phosphate. Many genes in these pathways are required for virulence in murine models of C. albicans infection ( Ramanan and Wang 2000 ; Donovan et al 2001 ; Jezewski et al 2007 ; Carlisle et al 2009 ; MacCallum et al 2009 ; Correia et al 2010 ; Jiang et al 2010 ; Mackie et al 2016 ). It is possible that the combination of effects on these multiple pathways in the grf10 Δ mutant led to strong attenuated virulence in mouse models of infection ( Romanowski et al 2012 ; Ghosh et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Grf10 regulates the response to copper, iron, and phosphate in Candida albicans

Wangsanut

Arnold

Jilani

et al. 2023

G3: Genes, Genomes, Genetics

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The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, one-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage dependent manner but grew the same as the wild-type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein-interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.

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Role of the Vps34p-interacting protein Ade5,7p in hyphal growth and virulence of Candida albicans

Cited by 6 publications

References 40 publications

Identification of factors involved in dimorphism and pathogenicity of Zymoseptoria tritici

Identification of factors involved in dimorphism and pathogenicity of Zymoseptoria tritici

Grf10 and Bas1 Regulate Transcription of Adenylate and One-Carbon Biosynthesis Genes and Affect Virulence in the Human Fungal Pathogen Candida albicans

Grf10 regulates the response to copper, iron, and phosphate in Candida albicans

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