Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence

ABSTRACT Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l-arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candi...

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Autores principales:	Katja Schaefer, Jeanette Wagener, Ryan M. Ames, Stella Christou, Donna M. MacCallum, Steven Bates, Neil A. R. Gow
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida arginase guanidinobutyrase agmatinase immunity morphogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a25cee59556847d1a07e1213bea9ad88
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spelling	oai:doaj.org-article:a25cee59556847d1a07e1213bea9ad882021-11-15T15:56:43ZThree Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence10.1128/mBio.01845-202150-7511https://doaj.org/article/a25cee59556847d1a07e1213bea9ad882020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01845-20https://doaj.org/toc/2150-7511ABSTRACT Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l-arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candida albicans can metabolize and grow on arginine, agmatine, or guanidinobutyrate as the sole nitrogen source. Three related C. albicans genes whose sequences suggested that they were putative arginase or arginase-like genes were examined for their role in these metabolic pathways. Of these, Car1 encoded the only bona fide arginase, whereas we provide evidence that the other two open reading frames, orf19.5862 and orf19.3418, encode agmatinase and guanidinobutyrase (Gbase), respectively. Analysis of strains with single and multiple mutations suggested the presence of arginase-dependent and arginase-independent routes for polyamine production. CAR1 played a role in hyphal morphogenesis in response to arginine, and the virulence of a triple mutant was reduced in both Galleria mellonella and Mus musculus infection models. In the bloodstream, arginine is an essential amino acid that is required by phagocytes to synthesize nitric oxide (NO). However, none of the single or multiple mutants affected host NO production, suggesting that they did not influence the oxidative burst of phagocytes. IMPORTANCE We show that the C. albicans ureohydrolases arginase (Car1), agmatinase (Agt1), and guanidinobutyrase (Gbu1) can orchestrate an arginase-independent route for polyamine production and that this is important for C. albicans growth and survival in microenvironments of the mammalian host.Katja SchaeferJeanette WagenerRyan M. AmesStella ChristouDonna M. MacCallumSteven BatesNeil A. R. GowAmerican Society for MicrobiologyarticleCandidaarginaseguanidinobutyraseagmatinaseimmunitymorphogenesisMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida arginase guanidinobutyrase agmatinase immunity morphogenesis Microbiology QR1-502
spellingShingle	Candida arginase guanidinobutyrase agmatinase immunity morphogenesis Microbiology QR1-502 Katja Schaefer Jeanette Wagener Ryan M. Ames Stella Christou Donna M. MacCallum Steven Bates Neil A. R. Gow Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
description	ABSTRACT Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l-arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candida albicans can metabolize and grow on arginine, agmatine, or guanidinobutyrate as the sole nitrogen source. Three related C. albicans genes whose sequences suggested that they were putative arginase or arginase-like genes were examined for their role in these metabolic pathways. Of these, Car1 encoded the only bona fide arginase, whereas we provide evidence that the other two open reading frames, orf19.5862 and orf19.3418, encode agmatinase and guanidinobutyrase (Gbase), respectively. Analysis of strains with single and multiple mutations suggested the presence of arginase-dependent and arginase-independent routes for polyamine production. CAR1 played a role in hyphal morphogenesis in response to arginine, and the virulence of a triple mutant was reduced in both Galleria mellonella and Mus musculus infection models. In the bloodstream, arginine is an essential amino acid that is required by phagocytes to synthesize nitric oxide (NO). However, none of the single or multiple mutants affected host NO production, suggesting that they did not influence the oxidative burst of phagocytes. IMPORTANCE We show that the C. albicans ureohydrolases arginase (Car1), agmatinase (Agt1), and guanidinobutyrase (Gbu1) can orchestrate an arginase-independent route for polyamine production and that this is important for C. albicans growth and survival in microenvironments of the mammalian host.
format	article
author	Katja Schaefer Jeanette Wagener Ryan M. Ames Stella Christou Donna M. MacCallum Steven Bates Neil A. R. Gow
author_facet	Katja Schaefer Jeanette Wagener Ryan M. Ames Stella Christou Donna M. MacCallum Steven Bates Neil A. R. Gow
author_sort	Katja Schaefer
title	Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
title_short	Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
title_full	Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
title_fullStr	Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
title_full_unstemmed	Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence
title_sort	three related enzymes in <named-content content-type="genus-species">candida albicans</named-content> achieve arginine- and agmatine-dependent metabolism that is essential for growth and fungal virulence
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/a25cee59556847d1a07e1213bea9ad88
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Three Related Enzymes in <named-content content-type="genus-species">Candida albicans</named-content> Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence

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