Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint

Gustavo Bravo Ruiz; Zoe K. Ross; Neil A. R. Gow; Alexander Lorenz

doi:10.1101/832931

Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint

Gustavo Bravo Ruiz, Zoe K. Ross, Neil A. R. Gow, Alexander Lorenz^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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, causes filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signalled 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.

Original language	English
Article number	e00151-20
Number of pages	17
Journal	mSphere
Volume	5
Issue number	2
DOIs	https://doi.org/10.1101/832931 https://doi.org/10.1128/mSphere.00151-20
Publication status	Published - 11 Mar 2020

Bibliographical note

We are grateful to Arunaloke Chakrabarti, Anuradha Chowdhary, Elizabeth Johnson (PHE), Takashi Kubota, and Shawn Lockhart (CDC) for providing strains. We thank Fei Long for skillful technical assistance. Flow cytometry was performed at the Iain Fraser Cytometry Centre (IFCC), University of Aberdeen (Raif Yuecel). Microscopy was done at the Microscopy & Histology Facility, University of Aberdeen (Kevin S. Mackenzie). This work was supported by a Wellcome Trust Seed Award to AL [grant number 212524/Z/18/Z], and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Exeter [grant numbers MR/P501955/1, MR/N006364/1].

Keywords

candida auris
filamentous growth
S phase checkpoint
Rad51
Rad9
Mrc1
Candida auris
Filamentous growth

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http://biorxiv.org/content/early/2019/11/06/832931.abstractLicence: CC BY-ND

Cite this

@article{303d29d37a274b3185907bee78b35cab,

title = "Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint",

abstract = "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, causes filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signalled 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.",

keywords = "candida auris, filamentous growth, S phase checkpoint, Rad51, Rad9, Mrc1, Candida auris, Filamentous growth",

author = "{Bravo Ruiz}, Gustavo and Ross, {Zoe K.} and Gow, {Neil A. R.} and Alexander Lorenz",

note = "We are grateful to Arunaloke Chakrabarti, Anuradha Chowdhary, Elizabeth Johnson (PHE), Takashi Kubota, and Shawn Lockhart (CDC) for providing strains. We thank Fei Long for skillful technical assistance. Flow cytometry was performed at the Iain Fraser Cytometry Centre (IFCC), University of Aberdeen (Raif Yuecel). Microscopy was done at the Microscopy & Histology Facility, University of Aberdeen (Kevin S. Mackenzie). This work was supported by a Wellcome Trust Seed Award to AL [grant number 212524/Z/18/Z], and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Exeter [grant numbers MR/P501955/1, MR/N006364/1].",

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doi = "10.1101/832931",

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AU - Bravo Ruiz, Gustavo

AU - Ross, Zoe K.

AU - Gow, Neil A. R.

AU - Lorenz, Alexander

N1 - We are grateful to Arunaloke Chakrabarti, Anuradha Chowdhary, Elizabeth Johnson (PHE), Takashi Kubota, and Shawn Lockhart (CDC) for providing strains. We thank Fei Long for skillful technical assistance. Flow cytometry was performed at the Iain Fraser Cytometry Centre (IFCC), University of Aberdeen (Raif Yuecel). Microscopy was done at the Microscopy & Histology Facility, University of Aberdeen (Kevin S. Mackenzie). This work was supported by a Wellcome Trust Seed Award to AL [grant number 212524/Z/18/Z], and the Medical Research Council (MRC) Centre for Medical Mycology at the University of Exeter [grant numbers MR/P501955/1, MR/N006364/1].

PY - 2020/3/11

Y1 - 2020/3/11

N2 - 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, causes filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signalled 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.

AB - 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, causes filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signalled 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.

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KW - filamentous growth

KW - S phase checkpoint

KW - Rad51

KW - Rad9

KW - Mrc1

KW - Candida auris

KW - Filamentous growth

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Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint

Abstract

Bibliographical note

Keywords

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Alexander Lorenz

Iain Fraser Cytometry Centre

Microscopy and Histology

Cite this

Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Profiles

Alexander Lorenz

Equipment

Iain Fraser Cytometry Centre

Microscopy and Histology

Cite this