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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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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