Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones

Aspergillus fumigatus is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the...

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Main Authors: Duaa Anabosi, Zohar Meir, Yana Shadkchan, Mariana Handelman, Ammar Abou-Kandil, Annie Yap, Daniel Urlings, Morgan S. Gold, Sven Krappmann, Hubertus Haas, Nir Osherov
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Virulence
Subjects:
Online Access:http://dx.doi.org/10.1080/21505594.2021.1958057
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spelling doaj-b36694be212d4034bf7dbe25b2a07ff72021-09-06T14:06:26ZengTaylor & Francis GroupVirulence2150-55942150-56082021-01-011212186220010.1080/21505594.2021.19580571958057Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperonesDuaa Anabosi0Zohar Meir1Yana Shadkchan2Mariana Handelman3Ammar Abou-Kandil4Annie Yap5Daniel Urlings6Morgan S. Gold7Sven Krappmann8Hubertus Haas9Nir Osherov10Sackler School of Medicine Ramat-AvivSackler School of Medicine Ramat-AvivSackler School of Medicine Ramat-AvivSackler School of Medicine Ramat-AvivSackler School of Medicine Ramat-AvivInstitute for Molecular Biology, Medical University InnsbruckSackler School of Medicine Ramat-AvivSackler School of Medicine Ramat-AvivClinical Microbiology, Immunology and Hygiene University Hospital and Friedrich-Alexander-University (FAU) of Erlangen-NürnbergInstitute for Molecular Biology, Medical University InnsbruckSackler School of Medicine Ramat-AvivAspergillus fumigatus is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the phagosomes of macrophages and neutrophils. We previously established that at high levels, Cu binds and activates the A. fumigatus transcription factor AceA, which upregulates the expression of the Cu exporter CrpA to expel excess Cu. Deletion of aceA or crpA result in extreme Cu sensitivity and attenuated virulence. To identify other elements participating in resistance to Cu, we performed a genome-wide analysis of the transcriptome by RNAseq to analyze the AceA-dependent response of A. fumigatus to excess Cu. We deleted key genes whose transcription was strongly upregulated by high Cu, including those encoding homologs of the three Cu chaperones cox17, atx1 and ccs1. Detailed analysis of these genes indicates that in A. fumigatus, cox17 is an essential gene with a possible role in respiration, the atxA gene product participates in reductive iron uptake and ccsA encodes the Cu chaperone activating A. fumigatus Sod1. Interestingly, although the ccsA-null strain was extremely sensitive to high Cu and oxidative stress, it was not attenuated in virulence in a mouse model of invasive pulmonary aspergillosis. Our work provides (i) a detailed view of the genome-wide transcriptional response of A. fumigatus to excess Cu, (ii) identification of the AceA-dependent transcriptome and (iii) analysis of the roles of the three Cu chaperones cox17, atxA and ccsA.http://dx.doi.org/10.1080/21505594.2021.1958057aspergillus fumigatuscu transcriptomecu chaperonesoxidative stressvirulence
collection DOAJ
language English
format Article
sources DOAJ
author Duaa Anabosi
Zohar Meir
Yana Shadkchan
Mariana Handelman
Ammar Abou-Kandil
Annie Yap
Daniel Urlings
Morgan S. Gold
Sven Krappmann
Hubertus Haas
Nir Osherov
spellingShingle Duaa Anabosi
Zohar Meir
Yana Shadkchan
Mariana Handelman
Ammar Abou-Kandil
Annie Yap
Daniel Urlings
Morgan S. Gold
Sven Krappmann
Hubertus Haas
Nir Osherov
Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
Virulence
aspergillus fumigatus
cu transcriptome
cu chaperones
oxidative stress
virulence
author_facet Duaa Anabosi
Zohar Meir
Yana Shadkchan
Mariana Handelman
Ammar Abou-Kandil
Annie Yap
Daniel Urlings
Morgan S. Gold
Sven Krappmann
Hubertus Haas
Nir Osherov
author_sort Duaa Anabosi
title Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
title_short Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
title_full Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
title_fullStr Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
title_full_unstemmed Transcriptional response of Aspergillus fumigatus to copper and the role of the Cu chaperones
title_sort transcriptional response of aspergillus fumigatus to copper and the role of the cu chaperones
publisher Taylor & Francis Group
series Virulence
issn 2150-5594
2150-5608
publishDate 2021-01-01
description Aspergillus fumigatus is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the phagosomes of macrophages and neutrophils. We previously established that at high levels, Cu binds and activates the A. fumigatus transcription factor AceA, which upregulates the expression of the Cu exporter CrpA to expel excess Cu. Deletion of aceA or crpA result in extreme Cu sensitivity and attenuated virulence. To identify other elements participating in resistance to Cu, we performed a genome-wide analysis of the transcriptome by RNAseq to analyze the AceA-dependent response of A. fumigatus to excess Cu. We deleted key genes whose transcription was strongly upregulated by high Cu, including those encoding homologs of the three Cu chaperones cox17, atx1 and ccs1. Detailed analysis of these genes indicates that in A. fumigatus, cox17 is an essential gene with a possible role in respiration, the atxA gene product participates in reductive iron uptake and ccsA encodes the Cu chaperone activating A. fumigatus Sod1. Interestingly, although the ccsA-null strain was extremely sensitive to high Cu and oxidative stress, it was not attenuated in virulence in a mouse model of invasive pulmonary aspergillosis. Our work provides (i) a detailed view of the genome-wide transcriptional response of A. fumigatus to excess Cu, (ii) identification of the AceA-dependent transcriptome and (iii) analysis of the roles of the three Cu chaperones cox17, atxA and ccsA.
topic aspergillus fumigatus
cu transcriptome
cu chaperones
oxidative stress
virulence
url http://dx.doi.org/10.1080/21505594.2021.1958057
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