Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>

ABSTRACT Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remainin...

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Autores principales:	Rafael Wesley Bastos, Clara Valero, Lilian Pereira Silva, Taylor Schoen, Milton Drott, Verônica Brauer, Rafael Silva-Rocha, Abigail Lind, Jacob L. Steenwyk, Antonis Rokas, Fernando Rodrigues, Agustin Resendiz-Sharpe, Katrien Lagrou, Marina Marcet-Houben, Toni Gabaldón, Erin McDonnell, Ian Reid, Adrian Tsang, Berl R. Oakley, Flávio Vieira Loures, Fausto Almeida, Anna Huttenlocher, Nancy P. Keller, Laure Nicolas Annick Ries, Gustavo H. Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus nidulans clinical isolates genome sequencing metabolomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6bd789c5c13847228c1a150b73b27800
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spelling	oai:doaj.org-article:6bd789c5c13847228c1a150b73b278002021-11-15T15:29:16ZFunctional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>10.1128/mSphere.00153-202379-5042https://doaj.org/article/6bd789c5c13847228c1a150b73b278002020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00153-20https://doaj.org/toc/2379-5042ABSTRACT Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, nonclinical FGSC A4 strain. Both CIs presented increased growth in comparison to that of the reference strain in the presence of physiologically relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall-perturbing agents but not to other physiologically relevant stresses. Genome analyses identified several frameshift variants in genes encoding cell wall integrity (CWI) signaling components. Significant differences in CWI signaling were confirmed by Western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function than the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just as in Aspergillus fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity. IMPORTANCE Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.Rafael Wesley BastosClara ValeroLilian Pereira SilvaTaylor SchoenMilton DrottVerônica BrauerRafael Silva-RochaAbigail LindJacob L. SteenwykAntonis RokasFernando RodriguesAgustin Resendiz-SharpeKatrien LagrouMarina Marcet-HoubenToni GabaldónErin McDonnellIan ReidAdrian TsangBerl R. OakleyFlávio Vieira LouresFausto AlmeidaAnna HuttenlocherNancy P. KellerLaure Nicolas Annick RiesGustavo H. GoldmanAmerican Society for MicrobiologyarticleAspergillus nidulansclinical isolatesgenome sequencingmetabolomicsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus nidulans clinical isolates genome sequencing metabolomics Microbiology QR1-502
spellingShingle	Aspergillus nidulans clinical isolates genome sequencing metabolomics Microbiology QR1-502 Rafael Wesley Bastos Clara Valero Lilian Pereira Silva Taylor Schoen Milton Drott Verônica Brauer Rafael Silva-Rocha Abigail Lind Jacob L. Steenwyk Antonis Rokas Fernando Rodrigues Agustin Resendiz-Sharpe Katrien Lagrou Marina Marcet-Houben Toni Gabaldón Erin McDonnell Ian Reid Adrian Tsang Berl R. Oakley Flávio Vieira Loures Fausto Almeida Anna Huttenlocher Nancy P. Keller Laure Nicolas Annick Ries Gustavo H. Goldman Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
description	ABSTRACT Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, nonclinical FGSC A4 strain. Both CIs presented increased growth in comparison to that of the reference strain in the presence of physiologically relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall-perturbing agents but not to other physiologically relevant stresses. Genome analyses identified several frameshift variants in genes encoding cell wall integrity (CWI) signaling components. Significant differences in CWI signaling were confirmed by Western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function than the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just as in Aspergillus fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity. IMPORTANCE Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.
format	article
author	Rafael Wesley Bastos Clara Valero Lilian Pereira Silva Taylor Schoen Milton Drott Verônica Brauer Rafael Silva-Rocha Abigail Lind Jacob L. Steenwyk Antonis Rokas Fernando Rodrigues Agustin Resendiz-Sharpe Katrien Lagrou Marina Marcet-Houben Toni Gabaldón Erin McDonnell Ian Reid Adrian Tsang Berl R. Oakley Flávio Vieira Loures Fausto Almeida Anna Huttenlocher Nancy P. Keller Laure Nicolas Annick Ries Gustavo H. Goldman
author_facet	Rafael Wesley Bastos Clara Valero Lilian Pereira Silva Taylor Schoen Milton Drott Verônica Brauer Rafael Silva-Rocha Abigail Lind Jacob L. Steenwyk Antonis Rokas Fernando Rodrigues Agustin Resendiz-Sharpe Katrien Lagrou Marina Marcet-Houben Toni Gabaldón Erin McDonnell Ian Reid Adrian Tsang Berl R. Oakley Flávio Vieira Loures Fausto Almeida Anna Huttenlocher Nancy P. Keller Laure Nicolas Annick Ries Gustavo H. Goldman
author_sort	Rafael Wesley Bastos
title	Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
title_short	Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
title_full	Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
title_fullStr	Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
title_full_unstemmed	Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>
title_sort	functional characterization of clinical isolates of the opportunistic fungal pathogen <named-content content-type="genus-species">aspergillus nidulans</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6bd789c5c13847228c1a150b73b27800
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Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen <named-content content-type="genus-species">Aspergillus nidulans</named-content>

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