<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity

ABSTRACT Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of a...

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Autores principales:	Laure Nicolas Annick Ries, Patricia Alves de Castro, Lilian Pereira Silva, Clara Valero, Thaila Fernanda dos Reis, Raquel Saborano, Iola F. Duarte, Gabriela Felix Persinoti, Jacob L. Steenwyk, Antonis Rokas, Fausto Almeida, Jonas Henrique Costa, Taicia Fill, Sarah Sze Wah Wong, Vishukumar Aimanianda, Fernando José Santos Rodrigues, Relber A. Gonçales, Cláudio Duarte-Oliveira, Agostinho Carvalho, Gustavo H. Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Aspergillus fumigatus acetate assimilation cell wall secondary metabolites transcription factor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0159b3f7f75a4c6cb40eb25bbdc84201
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spelling	oai:doaj.org-article:0159b3f7f75a4c6cb40eb25bbdc842012021-11-10T18:37:50Z<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity10.1128/mBio.01682-212150-7511https://doaj.org/article/0159b3f7f75a4c6cb40eb25bbdc842012021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01682-21https://doaj.org/toc/2150-7511ABSTRACT Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolized via different pathways in A. fumigatus and that acetate utilization is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilization is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, antifungal drugs, and human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilization in A. fumigatus, and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of antifungal strategies. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion. This work shows that A. fumigatus metabolizes acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus in vivo virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterizes acetate utilization in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.Laure Nicolas Annick RiesPatricia Alves de CastroLilian Pereira SilvaClara ValeroThaila Fernanda dos ReisRaquel SaboranoIola F. DuarteGabriela Felix PersinotiJacob L. SteenwykAntonis RokasFausto AlmeidaJonas Henrique CostaTaicia FillSarah Sze Wah WongVishukumar AimaniandaFernando José Santos RodriguesRelber A. GonçalesCláudio Duarte-OliveiraAgostinho CarvalhoGustavo H. GoldmanAmerican Society for MicrobiologyarticleAspergillus fumigatusacetate assimilationcell wallsecondary metabolitestranscription factorMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus acetate assimilation cell wall secondary metabolites transcription factor Microbiology QR1-502
spellingShingle	Aspergillus fumigatus acetate assimilation cell wall secondary metabolites transcription factor Microbiology QR1-502 Laure Nicolas Annick Ries Patricia Alves de Castro Lilian Pereira Silva Clara Valero Thaila Fernanda dos Reis Raquel Saborano Iola F. Duarte Gabriela Felix Persinoti Jacob L. Steenwyk Antonis Rokas Fausto Almeida Jonas Henrique Costa Taicia Fill Sarah Sze Wah Wong Vishukumar Aimanianda Fernando José Santos Rodrigues Relber A. Gonçales Cláudio Duarte-Oliveira Agostinho Carvalho Gustavo H. Goldman <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
description	ABSTRACT Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolized via different pathways in A. fumigatus and that acetate utilization is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilization is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, antifungal drugs, and human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilization in A. fumigatus, and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of antifungal strategies. IMPORTANCE Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion. This work shows that A. fumigatus metabolizes acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus in vivo virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterizes acetate utilization in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.
format	article
author	Laure Nicolas Annick Ries Patricia Alves de Castro Lilian Pereira Silva Clara Valero Thaila Fernanda dos Reis Raquel Saborano Iola F. Duarte Gabriela Felix Persinoti Jacob L. Steenwyk Antonis Rokas Fausto Almeida Jonas Henrique Costa Taicia Fill Sarah Sze Wah Wong Vishukumar Aimanianda Fernando José Santos Rodrigues Relber A. Gonçales Cláudio Duarte-Oliveira Agostinho Carvalho Gustavo H. Goldman
author_facet	Laure Nicolas Annick Ries Patricia Alves de Castro Lilian Pereira Silva Clara Valero Thaila Fernanda dos Reis Raquel Saborano Iola F. Duarte Gabriela Felix Persinoti Jacob L. Steenwyk Antonis Rokas Fausto Almeida Jonas Henrique Costa Taicia Fill Sarah Sze Wah Wong Vishukumar Aimanianda Fernando José Santos Rodrigues Relber A. Gonçales Cláudio Duarte-Oliveira Agostinho Carvalho Gustavo H. Goldman
author_sort	Laure Nicolas Annick Ries
title	<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
title_short	<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
title_full	<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
title_fullStr	<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
title_full_unstemmed	<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity
title_sort	<named-content content-type="genus-species">aspergillus fumigatus</named-content> acetate utilization impacts virulence traits and pathogenicity
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/0159b3f7f75a4c6cb40eb25bbdc84201
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<named-content content-type="genus-species">Aspergillus fumigatus</named-content> Acetate Utilization Impacts Virulence Traits and Pathogenicity

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