Aspergillus fumigatusHsp90 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 ^[1] ; Minari, Karine ^{[2, 1]} ; Fabri, Joao Henrique Tadini Marilhano ^[1] ; Kerkaert, Joshua D. ^[3] ; Gava, Lisandra Marques ^[1] ; da Cunha, Anderson Ferreira ^[1] ; Cramer, Robert A. ^[3] ; Borges, Julio Cesar ^[2] ; Malavazi, Iran ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Genet & Evolucao, Ctr Ciencias Biol & Saude, Sao Carlos - Brazil

^[2] Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos - Brazil

^[3] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH - USA

• Document type: Journal article
• Source: Cellular Microbiology; v. 23, n. 2 FEB 2021.
• Web of Science Citations: 1

Abstract

The initiation ofAspergillus fumigatusinfection 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. AlthoughA. fumigatusis 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 inA. fumigatusthermotolerance. 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 forA. fumigatusto cope with the temperature increase found in the mammalian lung environment, emphasising the importance of this pathway in supporting thermotolerance and cell wall integrity. (AU)

• FAPESP's process: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/07206-6 - Studies of the mitochondrial HSP70 of human and protozoa: structural and functional approaches
• Grantee: Julio Cesar Borges
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/19694-3 - The role of heat shock proteins HsfA and Hsp90 and the regulator SmiA at cell wall integrity pathway activity in the opportunistic human pathogen Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/17541-0 - Study of the relationship between genes involved in the cell wall integrity maintenance and thermotolerance in the human pathogenic fungi Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis
• Grantee: Carlos Henrique Inacio Ramos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/07335-9 - Studies of human HSP70 isoforms residing in the cytoplasm and mitochondria and their high molecular weight oligomers: interaction with co-chaperones and client proteins
• Grantee: Julio Cesar Borges
• Support Opportunities: Regular Research Grants