G1 and S phase arrest in <i>Candida albicans</i> induces filamentous growth via distinct mechanisms

Chen, Cuilan; Zeng, Guisheng; Wang, Yan Ming

doi:10.1111/mmi.14097

Cited by 18 publications

(24 citation statements)

References 58 publications

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“…This process involves ϳ700 genes for pseudohypha formation in S. cerevisiae (27,28) and more than 2,000 genes in C. albicans filamentous growth (29). However, mutation of key genes regulating filamentous growth, such as HGC1, UME6, FLO8, TEC1, NRG1, CPH1 (STE12 in S. cerevisiae), or EFG1, does not affect HU-induced pseudohypha formation (19,49,50). Therefore, pseudohyphal growth upon genotoxic stress apparently involves, at least partially, different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Pseudohyphal Growth of the Emerging Pathogen Candida auris Is Triggered by Genotoxic Stress through the S Phase Checkpoint

Ruiz

Ross

Gow

et al. 2020

mSphere

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The morphogenetic switching between yeast cells and filaments (true hyphae and pseudohyphae) is a key cellular feature required for full virulence in many polymorphic fungal pathogens, such as Candida albicans. In the recently emerged yeast pathogen Candida auris, occasional elongation of cells has been reported. However, environmental conditions and genetic triggers for filament formation have remained elusive. Here, we report that induction of DNA damage and perturbation of replication forks by treatment with genotoxins, such as hydroxyurea, methyl methanesulfonate, and the clinically relevant fungistatic 5-fluorocytosine, cause filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signaled through the S phase checkpoint and, interestingly, is Tup1 independent in C. auris. Intriguingly, the morphogenetic switching capability is strain specific in C. auris, highlighting the heterogenous nature of the species as a whole. IMPORTANCE Candida auris is a newly emerged fungal pathogen of humans. This species was first reported in 2009 when it was identified in an ear infection of a patient in Japan. However, despite intense interest in this organism as an often multidrug-resistant fungus, there is little knowledge about its cellular biology. During infection of human patients, fungi are able to change cell shape from ellipsoidal yeast cells to elongated filaments to adapt to various conditions within the host organism. There are different types of filaments, which are triggered by reactions to different cues. Candida auris fails to form filaments when exposed to triggers that stimulate yeast filament morphogenesis in other fungi. Here, we show that it does form filaments when its DNA is damaged. These conditions might arise when Candida auris cells interact with host immune cells or during growth in certain host tissues (kidney or bladder) or during treatment with antifungal drugs.

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Section: Discussionmentioning

confidence: 99%

“…Hence, mutation of CLB2, CDC28, and CDC5 triggers constitutive pseudohyphal growth in yeasts (49,70,71). Furthermore, the cAMP and MAPK pathways have been implicated in pseudohyphal growth in response to genotoxic stress via downstream regulators (18,42,50,72). A plausible model for C. auris is depicted in Fig.…”

Section: Discussionmentioning

confidence: 99%

Pseudohyphal Growth of the Emerging Pathogen Candida auris Is Triggered by Genotoxic Stress through the S Phase Checkpoint

Ruiz

Ross

Gow

et al. 2020

mSphere

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“…The pathways for hyphal induction upon interference with the cell cycle progression include the transcription factor Ume6 and the Cdc28 cyclin Hgc1 in the case of the depletion of Cdc5 or Cln3, but not for hydroxyurea-induced filamentous growth. The latter, however, still required the Ras-cAMP pathway activity [133,134]. HSG expression induced by diminished CAK1 expression was surprisingly resistant to the deletion of TFs that are normally essential for hyphal growth under many conditions, in particular, Ume6 and Brg1.…”

Section: Regulation Of Hyphal Morphogenesis and Hsg Expression By mentioning

confidence: 99%

Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals

Kornitzer

2019

JoF

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Candida albicans is a human commensal fungus that is able to assume several morphologies, including yeast, hyphal, and pseudohyphal. Under a range of conditions, C. albicans performs a regulated switch to the filamentous morphology, characterized by the emergence of a germ tube from the yeast cell, followed by a mold-like growth of branching hyphae. This transition from yeast to hyphal growth has attracted particular attention, as it has been linked to the virulence of C. albicans as an opportunistic human pathogen. Signal transduction pathways that mediate the induction of the hyphal transcription program upon the imposition of external stimuli have been extensively investigated. However, the hyphal morphogenesis transcription program can also be induced by internal cellular signals, such as inhibition of cell cycle progression, and conversely, the inhibition of hyphal extension can repress hyphal-specific gene expression, suggesting that endogenous cellular signals are able to modulate hyphal gene expression as well. Here we review recent developments in the regulation of the hyphal morphogenesis of C. albicans, with emphasis on endogenous morphogenetic signals.

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“…Also, an investigation into the cAMP requirement for hyphal morphogenesis showed that basal levels of cAMP are sufficient for hyphal formation in response to N -acetylglucosamine (GlcNAc), suggesting that cAMP-independent signals are also important for hyphal induction 47 . Both G 1 and S phase arrest can induce filamentous growth and this has been shown to require the cAMP/PKA pathway 48 .…”

Section: Hyphal Growth Signalingmentioning

confidence: 99%

Recent advances in understanding Candida albicans hyphal growth

Arkowitz

Bassilana

2019

F1000Res

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Morphological changes are critical for the virulence of a range of plant and human fungal pathogens. Candida albicans is a major human fungal pathogen whose ability to switch between different morphological states is associated with its adaptability and pathogenicity. In particular, C. albicans can switch from an oval yeast form to a filamentous hyphal form, which is characteristic of filamentous fungi. What mechanisms underlie hyphal growth and how are they affected by environmental stimuli from the host or resident microbiota? These questions are the focus of intensive research, as understanding C. albicans hyphal growth has broad implications for cell biological and medical research.

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G1 and S phase arrest in Candida albicans induces filamentous growth via distinct mechanisms

Cited by 18 publications

References 58 publications

Pseudohyphal Growth of the Emerging Pathogen Candida auris Is Triggered by Genotoxic Stress through the S Phase Checkpoint

Pseudohyphal Growth of the Emerging Pathogen Candida auris Is Triggered by Genotoxic Stress through the S Phase Checkpoint

Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals

Recent advances in understanding Candida albicans hyphal growth

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