Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence

Author(s):Show less -

Rocha, Marina Campos ^[1] ; de Godoy, Krissia Franco ^[1] ; Bannitz-Fernandes, Renata ^[2] ; Marilhano Fabri, Joao H. T. ^[1] ; Ferrari Barbosa, Mayra M. ^{[1, 3]} ; de Castro, Patricia Alves ^[4] ; Almeida, Fausto ^[5] ; Goldman, Gustavo Henrique ^[4] ; da Cunha, Anderson Ferreira ^[1] ; Netto, Luis E. S. ^[2] ; de Oliveira, Marcos Antonio ^[6] ; Malavazi, Iran ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Genet & Evolucao, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo, SP - Brazil

^[3] Inst Butantan, BR-05503900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14040900 Ribeirao Preto, SP - Brazil

^[6] Univ Estadual Paulista, Inst Biociencias, Campus Litoral Paulista, BR-11380972 Sao Vicente, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, AUG 17 2018.
• Web of Science Citations: 5

Abstract

Standing among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence and persistence of pathogens in distinct hosts. Here, we revealed that the opportunistic human pathogen A. fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol. As observed for other Prxs, recombinant Prx1 and PrxC decomposed H2O2 at elevated velocities (rate constants in the 10(7) M(-1)s(-1) range). Deletion mutants for each Prx displayed higher sensitivity to oxidative challenge in comparison with the wild-type strain. Additionally, cytosolic Prx1 was important for A. fumigatus survival upon electron transport dysfunction. Expression of Prxs was dependent on the SakA(HOG1) MAP kinase and the Yap1(YAP1) transcription factor, a global regulator of the oxidative stress response in fungi. Finally, cytosolic Prx1 played a major role in pathogenicity, since it is required for full virulence, using a neutropenic mouse infection model. Our data indicate that the three 1-Cys Prxs act together to maintain the redox balance of A. fumigatus. (AU)

• FAPESP's process: 16/03322-7 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support type: Research Grants - Young Investigators 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 type: Regular Research Grants
• FAPESP's process: 13/22375-6 - Biochemical and functional characterization of the transcription factor rlmA and the interaction of pkcA and Hsp90 in the fungus Aspergillus fumigatus
• Grantee: Marina Campos Rocha
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/16636-4 - Functional analysis of peroxiredoxins in the human opportunistic fungal pathogen Aspergillus fumigatus
• Grantee: Krissia Franco de Godoy
• Support type: Scholarships in Brazil - Master