Transcription factor Afmac1 controls copper import machinery in Aspergillus fumigatus

Kusuya, Yoko; Hagiwara, Daisuke; Sakai, Kanae; Yaguchi, Takashi; Gonoi, Tohru; Takahashi, Hiroki

doi:10.1007/s00294-017-0681-z

Cited by 31 publications

(30 citation statements)

References 46 publications

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“…The strain used in this study was A. fumigatus Af293. Potato dextrose agar (PDA; Difco, Detroit, USA), YG [ 27 ], and AMM [ 52 ] were regularly used for culturing the strain. To collect fresh conidia, the stored conidia were incubated on a PDA plate at 30 °C, or an AMM at 37 °C for 1 week.…”

Section: Methodsmentioning

confidence: 99%

Global gene expression reveals stress-responsive genes in Aspergillus fumigatus mycelia

et al. 2017

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Background Aspergillus fumigatus is a human fungal pathogen that causes aspergillosis in immunocompromised hosts. A. fumigatus is believed to be exposed to diverse environmental stresses in the host cells. The adaptation mechanisms are critical for infections in human bodies. Transcriptional networks in response to diverse environmental challenges remain to be elucidated. To gain insights into the adaptation to environmental stresses in A. fumigatus mycelia, we conducted time series transcriptome analyses.ResultsWith the aid of RNA-seq, we explored the global gene expression profiles of mycelia in A. fumigatus upon exposure to diverse environmental changes, including heat, superoxide, and osmotic stresses. From the perspective of global transcriptomes, transient responses to superoxide and osmotic stresses were observed while responses to heat stresses were gradual. We identified the stress-responsive genes for particular stresses, and the 266 genes whose expression levels drastically fluctuated upon exposure to all tested stresses. Among these, the 77 environmental stress response genes are conserved in S. cerevisiae, suggesting that these genes might be more general prerequisites for adaptation to environmental stresses. Finally, we revealed the strong correlations among expression profiles of genes related to ‘rRNA processing’.ConclusionsThe time series transcriptome analysis revealed the stress-responsive genes underlying the adaptation mechanisms in A. fumigatus mycelia. These results will shed light on the regulatory networks underpinning the adaptation of the filamentous fungi.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4316-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Global gene expression reveals stress-responsive genes in Aspergillus fumigatus mycelia

et al. 2017

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“…Metal responsive transcription factors are able to sense the copper concentration within the cell and orchestrate a response by activating the copper import or copper detoxification, as required. These two regulatory paths are under the control of two separate transcription factors (Keller et al 2005) which were first discovered in S. cerevisiae as Mac1 and Ace1 (Balamurugan and Schaffner 2006), and later described in A. nidulans and A. fumigatus (Antsotegi-Uskola et al 2017;Cai et al 2019;Kusuya et al 2017;Wiemann et al 2017).…”

Section: Genetic Regulation Of Copper Homeostasismentioning

confidence: 99%

“…The N-terminal region contains a RGHR and GRP motifs and the BCu fist^domain, all together, they are responsible of the Cudependent DNA binding of the TF (Cai et al 2017). A Cterminal copper binding domain with two cysteine-rich motifs is responsible for copper sensing (Kusuya et al 2017). Sitedirected mutagenesis studies in A. fumigatus and A. nidulans have demonstrated that Cys residues of the N-terminal BCu fist^domain are essential for MacA DNA binding (Cai et al 2019).…”

Section: Genetic Regulation Of Copper Homeostasismentioning

confidence: 99%

“…It has recently been reported that AfMacA also regulates iron homeostasis and its localization in the cell varies depending on copper and iron concentration (Park et al 2018). AfmacA disruption generated a copper starvation phenotype with manifest growth defects in copper depletion conditions (Cai et al 2017;Kusuya et al 2017;Park et al 2017).…”

Section: Genetic Regulation Of Copper Homeostasismentioning

confidence: 99%

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New insights into copper homeostasis in filamentous fungi

Antsotegi-Uskola

Markina-Iñarrairaegui

Ugalde

2019

Int Microbiol

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Copper is a metal ion that is required as a micronutrient for growth and proliferation. However, copper accumulation generates toxicity by multiple mechanisms, potentially leading to cell death. Due to its toxic nature at high concentrations, different chemical variants of copper have been extensively used as antifungal agents in agriculture and medicine. Most studies on copper homeostasis have been carried out in bacteria, yeast, and mammalian organisms. However, knowledge on filamentous fungi is less well documented. This review summarizes the knowledge gathered in the last few years about copper homeostasis in the filamentous fungi Aspergillus fumigatus and Aspergillus nidulans: The mechanism of action of copper, the uptake and detoxification systems, their regulation at the transcriptional level, and the role of copper homeostasis in fungal pathogenicity are presented.

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“…As with other pathogenic microorganisms, metal homeostasis is closely related to the virulence of A. fumigatus [ 7 , 8 , 9 ]. In particular, copper has an important role in the growth of conidia [ 10 , 11 , 12 ], which directly affects the virulence of A. fumigatus , and the copper-responsive transcription factor AfMac1 is known to be directly related to the virulence of A. fumigatus [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Zinc in Copper Homeostasis of Aspergillus fumigatus

Kang

Seo

Moon

et al. 2020

IJMS

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Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the Δafmac1 strain on AMM. In addition, the growth defect of the Δafmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the Δafmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the Δafmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5′-CAA(G)GGT-3′ was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.

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Transcription factor Afmac1 controls copper import machinery in Aspergillus fumigatus

Cited by 31 publications

References 46 publications

Global gene expression reveals stress-responsive genes in Aspergillus fumigatus mycelia

Global gene expression reveals stress-responsive genes in Aspergillus fumigatus mycelia

New insights into copper homeostasis in filamentous fungi

The Role of Zinc in Copper Homeostasis of Aspergillus fumigatus

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