Derepressed Hyphal Growth and Reduced Virulence in a VH1 Family-related Protein Phosphatase Mutant of the Human Pathogen<i>Candida albicans</i>

Csank, Csilla; Makris, Constantin; Meloche, Sylvain; Schröppel, Klaus; Röllinghoff, Martin; Dignard, Daniel; Thomas, David Y.; Whiteway, Malcolm

doi:10.1091/mbc.8.12.2539

Cited by 105 publications

(113 citation statements)

References 63 publications

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“…In addition to these components, a MAP kinase phosphatase, Cpp1, has been identified which regulates filamentous growth in C. albicans (62). Disruption of both alleles of the CPP1 gene derepresses hyphal production and results in a hyperfilamentous phenotype.…”

Section: Map Kinase Signaling Pathwaymentioning

confidence: 99%

Signal Transduction Cascades Regulating Fungal Development and Virulence

Lengeler

Davidson

D’Souza

et al. 2000

Microbiol Mol Biol Rev

837

774

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SUMMARY Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous growth referred to as pseudohyphal differentiation. Yeast filamentous growth is regulated, in part, by two conserved signal transduction cascades: a mitogen-activated protein kinase cascade and a G-protein regulated cyclic AMP signaling pathway. Related signaling cascades play an analogous role in regulating mating and virulence in the plant fungal pathogen Ustilago maydis and the human fungal pathogens Cryptococcus neoformans and Candida albicans. We review here studies on the signaling cascades that regulate development of these and other fungi. This analysis illustrates both how the model yeast S. cerevisiae can serve as a paradigm for signaling in other organisms and also how studies in other fungi provide insights into conserved signaling pathways that operate in many divergent organisms.

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Section: Map Kinase Signaling Pathwaymentioning

confidence: 99%

Signal Transduction Cascades Regulating Fungal Development and Virulence

Lengeler

Davidson

D’Souza

et al. 2000

Microbiol Mol Biol Rev

837

774

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“…This organism can switch between several morphological forms including yeast, pseudohyphae, and hyphae (Berman and Sudbery, 2002;Sudbery et al, 2004). The yeast-hypha transition has attracted much attention because of its established importance for infection and virulence (Csank et al, 1997;Lo et al, 1997;Gale et al, 1998;Gow et al, 2002;Zheng et al, 2004). Several signal-transduction pathways are known to play roles in growth-form selection (Liu, 2001;Berman and Sudbery, 2002).…”

Section: Introductionmentioning

confidence: 99%

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

Shi

Wang

Zheng

et al. 2007

MBoC

119

198

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The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotidereductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA-replication checkpoint, impaired DNA synthesis and caused cell elongation even in the absence of external genotoxic insults. Together, the results indicate that the DNA-replication/damage checkpoints are critically required for the induction of filamentous growth by genotoxic stress. In addition, either of two mutations in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the filamentous-growth response but had no significant deleterious effect on cell-cycle arrest. These results suggest that the FHA domain, known for its ability to bind phosphopeptides, has an important role in mediating genotoxic-stress-induced filamentous growth and that such growth is a specific, Rad53p-regulated cellular response in C. albicans. INTRODUCTIONThe polymorphic fungus Candida albicans has proven to be a very useful model for the study of cell morphogenesis (Odds, 1994;Sudbery et al., 2004;Wightman et al., 2004;Zheng et al., 2004). This organism can switch between several morphological forms including yeast, pseudohyphae, and hyphae (Berman and Sudbery, 2002;Sudbery et al., 2004). The yeast-hypha transition has attracted much attention because of its established importance for infection and virulence (Csank et al., 1997;Lo et al., 1997;Gale et al., 1998;Gow et al., 2002;Zheng et al., 2004). Several signal-transduction pathways are known to play roles in growth-form selection (Liu, 2001;Berman and Sudbery, 2002). The cAMPprotein kinase A (PKA) pathway has a key role, because blocking it abolishes true hyphal growth under most experimental conditions (Lo et al., 1997;Stoldt et al., 1997;Rocha et al., 2001). Another important pathway contains a MAPkinase cascade that seems to have a more important role in regulating pseudohyphal than true hyphal growth (Liu et al., 1994). The two pathways control the transcription factors Efg1p and Cph1p, respectively, which activate the expression of hypha-specific genes for a suite of infection-related functions (Lane et al., 2001).A diverse range of environmental stimuli can induce C. albicans hyphal or pseudohyphal growth, such as serum, neutral pH, appropriate temperature, certain amino acids and sugars, and some synthetic growth media (Ernst, 2000;Sudbery et al., 2004). These conditions more-or-less mimic certain host c...

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“…C. albicans protein phosphatases so far reported include Cyr1p/Orf19.5148 (Jain et al, 2003;Mallet et al, 2000), Cpp1p/Orf19.4866 (Csank et al, 1997), Cmp2p/Orf19.6033 (Blankenship et al, 2003;Sanglard et al, 2003) and Sit4p/Orf19.5200 (Lee et al, 2004), which were characterized from the phenotypes of disruptants of these genes. CYR1 encodes an adenyl cyclase, which functions in the Efg1-mediated pathway of morphological transition, although it is similar to the protein phosphatase 2C subclass (Jain et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…CYR1 encodes an adenyl cyclase, which functions in the Efg1-mediated pathway of morphological transition, although it is similar to the protein phosphatase 2C subclass (Jain et al, 2003). CPP1 encodes a DSP, which is involved in the repression of the hyphal signalling pathway, and may directly act on MAP kinase Cek1p (Csank et al, 1997). CMP2 encodes calcineurin, which is essential for cell tolerance to various growth inhibitors (Sanglard et al, 2003), and cell viability in a serum-based growth medium (Blankenship et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

et al. 2005

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In response to stimulants, such as serum, the yeast cells of the opportunistic fungal pathogen Candida albicans form germ tubes, which develop into hyphae. Yvh1p, one of the 29 protein phosphatases encoded in the C. albicans genome, has 45 % identity with the dual-specific phosphatase Yvh1p of the model yeast Saccharomyces cerevisiae. In this study, Yvh1p expression was not observed during the initial step of germ tube formation, although Yvh1p was expressed constitutively in cell cycle progression of yeast or hyphal cells. In an attempt to analyse the function of Yvh1p phosphatase, the complete ORFs of both alleles were deleted by replacement with hph200-URA3-hph200 and ARG4. Although YVH1 has nine single-nucleotide polymorphisms in its coding sequence, both YVH1 alleles were able to complement the YVH1 gene disruptant. The vegetative growth of Dyvh1 was significantly slower than the wild-type. The hyphal growth of Dyvh1 on agar, or in a liquid medium, was also slower than the wild-type because of the delay in nuclear division and septum formation, although germ tube formation was similar between the wild-type and the disruptant. Despite the slow hyphal growth, the expression of several hypha-specific genes in Dyvh1 was not delayed or repressed compared with that of the wild-type. Infection studies using mouse models revealed that the virulence of Dyvh1 was less than that of the wild-type. Thus, YVH1 contributes to normal vegetative yeast or hyphal cell cycle progression and pathogenicity, but not to germ tube formation.

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Derepressed Hyphal Growth and Reduced Virulence in a VH1 Family-related Protein Phosphatase Mutant of the Human PathogenCandida albicans

Cited by 105 publications

References 63 publications

Signal Transduction Cascades Regulating Fungal Development and Virulence

Signal Transduction Cascades Regulating Fungal Development and Virulence

Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth inCandida albicans

A putative dual-specific protein phosphatase encoded by YVH1 controls growth, filamentation and virulence in Candida albicans

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