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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Aspergillusfumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence

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Autor(es):
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Manfiolli, Adriana Oliveira [1] ; de Castro, Patricia Alves [1] ; dos Reis, Thaila Fernanda [1] ; Dolan, Stephen [2] ; Doyle, Sean [2] ; Jones, Gary [2] ; Riano Pachon, Diego M. [3] ; Ulas, Mevluet [2] ; Noble, Luke M. [4] ; Mattern, Derek J. [5, 6] ; Brakhage, Axel A. [6, 5] ; Valiante, Vito [7] ; Silva-Rocha, Rafael [8] ; Bayram, Ozgur [2] ; Goldman, Gustavo H. [1]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil
[2] Maynooth Univ, Dept Biol, Maynooth, Kildare - Ireland
[3] CNPEM, Lab Nacl Ciencia & Tecnol Bioetanol CTBE, Campinas, SP - Brazil
[4] NYU, New York, NY - USA
[5] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, Jena - Germany
[6] Univ Jena, Jena - Germany
[7] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Leibniz Res Grp Biobricks Microbial Nat Prod Synt, Jena - Germany
[8] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: Cellular Microbiology; v. 19, n. 12 DEC 2017.
Citações Web of Science: 12
Resumo

Metal restriction imposed by mammalian hosts during an infection is a common mechanism of defence to reduce or avoid the pathogen infection. Metals are essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis, a disease that typically manifests in immunocompromised patients. A.fumigatus PpzA, the catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as associated with iron assimilation. A.fumigatus has 2 high-affinity mechanisms of iron acquisition during infection: reductive iron assimilation and siderophore-mediated iron uptake. It has been shown that siderophore production is important for A.fumigatus virulence, differently to the reductive iron uptake system. Transcriptomic and proteomic comparisons between ppzA and wild-type strains under iron starvation showed that PpzA has a broad influence on genes involved in secondary metabolism. Liquid chromatography-mass spectrometry under standard and iron starvation conditions confirmed that the ppzA mutant had reduced production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl-fusarinine C, and helvolic acid. The Delta ppzA was shown to be avirulent in a neutropenic murine model of invasive pulmonary aspergillosis. PpzA plays an important role at the interface between iron starvation, regulation of SM production, and pathogenicity in A.fumigatus. (AU)

Processo FAPESP: 12/23942-9 - A função de genes que codificam fosfatases na virulência e na patogenicidade de Aspergillus fumigatus
Beneficiário:Gustavo Henrique Goldman
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 14/24951-7 - Identificação de alvos regulados pela fosfatase PhzA de Aspergillus fumigatus
Beneficiário:Adriana Oliveira Manfiolli
Linha de fomento: Bolsas no Brasil - Pós-Doutorado