Open AccessAspergillus fumigatus Hsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation
Author(s) -
Rocha Marina Campos,
Minari Karine,
Fabri João Henrique Tadini Marilhano,
Kerkaert Joshua D.,
Gava Lisandra Marques,
Cunha Anderson Ferreira,
Cramer Robert A.,
Borges Júlio César,
Malavazi Iran
Publication year - 2021
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13273
Subject(s) - aspergillus fumigatus , biology , hsp90 , heat shock protein , microbiology and biotechnology , hsp90 inhibitor , cell wall , chaperone (clinical) , biochemistry , gene , medicine , pathology
The initiation of Aspergillus fumigatus infection occurs via dormant conidia deposition into the airways. Therefore, conidial germination and subsequent hyphal extension and growth occur in a sustained heat shock (HS) environment promoted by the host. The cell wall integrity pathway (CWIP) and the essential eukaryotic chaperone Hsp90 are critical for fungi to survive HS. Although A. fumigatus is a thermophilic fungus, the mechanisms underpinning the HS response are not thoroughly described and important to define its role in pathogenesis, virulence and antifungal drug responses. Here, we investigate the contribution of the CWIP in A. fumigatus thermotolerance. We observed that the CWIP components PkcA, MpkA and RlmA are Hsp90 clients and that a PkcA G579R mutation abolishes this interaction. PkcA G579R also abolishes MpkA activation in the short‐term response to HS. Biochemical and biophysical analyses indicated that Hsp90 is a dimeric functional ATPase, which has a higher affinity for ADP than ATP and prevents MpkA aggregation in vitro. Our data suggest that the CWIP is constitutively required for A. fumigatus to cope with the temperature increase found in the mammalian lung environment, emphasising the importance of this pathway in supporting thermotolerance and cell wall integrity.