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

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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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, AUG 17 2018.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 09/53546-5 - Caracterização molecular da via de sinalização celular mediada pela proteína Quinase C no fungo patogênico humano Aspergillus fumigatus
• Beneficiário: Iran Malavazi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/16636-4 - Análise funcional das peroxirredoxinas no fungo patogênico oportunista humano Aspergillus fumigatus
• Beneficiário: Krissia Franco de Godoy
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/03322-7 - Papel de galectina-3 na infecção por Cryptococcus neoformans
• Beneficiário: Fausto Bruno dos Reis Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/17541-0 - Estudo da relação da via da integridade da parede celular e de genes de resposta ao estresse térmico no fungo patogênico humano Aspergillus fumigatus
• Beneficiário: Iran Malavazi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/22375-6 - Caracterização funcional e bioquímica do fator de transcrição rlmA e da interação de PkcA e Hsp90 no fungo Aspergillus fumigatus
• Beneficiário: Marina Campos Rocha
• Modalidade de apoio: Bolsas no Brasil - Doutorado