Journal
CELLULAR MICROBIOLOGY
Volume 20, Issue 10, Pages -Publisher
WILEY
DOI: 10.1111/cmi.12864
Keywords
AceA; Aspergillus fumigatus; copper (Cu); CrpA; transporter; virulence; zinc (Zn); ZrcA
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Funding
- National Natural Science Foundation of China [81330035, 31770086]
- China Postdoctoral Science Foundation [2016M591876]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Program for Jiangsu excellent scientific and technological innovation team [17CXTD00014]
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Copper (Cu) and zinc (Zn) are essential nutrients for both pathogens and hosts; however, their excess accumulation is toxic for all cells. The Aspergillus transcription factor AceA has been identified having function for Cu detoxification through up-regulation of the expression of the P-type ATPase, CrpA. Here, we demonstrate that Aspergillus fumigatus CrpA is involved in both Cu and Zn detoxification and a putative metallothionein AfCrdA plays a major function in Cu detoxification, and a putative transporter AfZrcA has a dominant role in Zn detoxification, but all three members are transcriptionally dependent on AfAceA. Moreover, the Cys, RGHR, and KGRP motifs in the conserved N-terminus of AfAceA are essential, but not sufficient for AfAceA-mediated Cu and Zn tolerance. Our findings suggest that fungal pathogens have developed very precise systems with overlapping machinery to respond to the two different metal stressors. Meanwhile, there is separate specific machinery for Zn detoxification in response to high environmental Zn. Importantly, virulence testing demonstrated that the conserved Cu and Zn detoxification-related Cys residues in AfAceA have key roles in pathogenesis. Therefore, these findings will broaden the current understanding of the adaption of saprophytic fungi to Cu and Zn stress and their survival in hosts and other environmental niches.
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