Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> 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 c...

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Autores principales:	Gustavo Bravo Ruiz, Zoe K. Ross, Neil A. R. Gow, Alexander Lorenz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida auris filamentous growth S phase checkpoint Rad51 Rad9 Mrc1 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b3e0ba1cb782473cb894fbf091bcec13
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spelling	oai:doaj.org-article:b3e0ba1cb782473cb894fbf091bcec132021-11-15T15:29:16ZPseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint10.1128/mSphere.00151-202379-5042https://doaj.org/article/b3e0ba1cb782473cb894fbf091bcec132020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00151-20https://doaj.org/toc/2379-5042ABSTRACT 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.Gustavo Bravo RuizZoe K. RossNeil A. R. GowAlexander LorenzAmerican Society for MicrobiologyarticleCandida aurisfilamentous growthS phase checkpointRad51Rad9Mrc1MicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida auris filamentous growth S phase checkpoint Rad51 Rad9 Mrc1 Microbiology QR1-502
spellingShingle	Candida auris filamentous growth S phase checkpoint Rad51 Rad9 Mrc1 Microbiology QR1-502 Gustavo Bravo Ruiz Zoe K. Ross Neil A. R. Gow Alexander Lorenz Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
description	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, 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.
format	article
author	Gustavo Bravo Ruiz Zoe K. Ross Neil A. R. Gow Alexander Lorenz
author_facet	Gustavo Bravo Ruiz Zoe K. Ross Neil A. R. Gow Alexander Lorenz
author_sort	Gustavo Bravo Ruiz
title	Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
title_short	Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
title_full	Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
title_fullStr	Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
title_full_unstemmed	Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint
title_sort	pseudohyphal growth of the emerging pathogen <named-content content-type="genus-species">candida auris</named-content> is triggered by genotoxic stress through the s phase checkpoint
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b3e0ba1cb782473cb894fbf091bcec13
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Pseudohyphal Growth of the Emerging Pathogen <named-content content-type="genus-species">Candida auris</named-content> Is Triggered by Genotoxic Stress through the S Phase Checkpoint

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