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Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner

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Annick Ries, Laure Nicolas [1] ; Steenwyk, Jacob L. [2] ; de Castro, Patricia Alves [3] ; Almeida de Lima, Pollyne Borborema [3] ; Almeida, Fausto [1] ; de Assis, Leandro Jose [3] ; Manfiolli, Adriana Oliveira [3] ; Takahashi-Nakaguchi, Azusa [4] ; Kusuya, Yoko [4] ; Hagiwara, Daisuke [4] ; Takahashi, Hiroki [4] ; Wang, Xi [5] ; Obar, Joshua J. [5] ; Rokas, Antonis [2] ; Goldman, Gustavo H. [3]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Sao Paulo - Brazil
[2] Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37235 - USA
[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil
[4] Chiba Univ, Med Mycol Res Ctr, Chiba - Japan
[5] Dartmouth Geisel Sch Med, Dept Microbiol & Immunol, Lebanon, NH - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Citações Web of Science: 0

Acquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner. (AU)

Processo FAPESP: 16/03322-7 - Papel de galectina-3 na infecção por Cryptococcus neoformans
Beneficiário:Fausto Bruno dos Reis Almeida
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 17/14159-2 - O papel do metabolismo da lactose e do acetato na virulência de Aspergillus fumigatus
Beneficiário:Laure Nicolas Annick Ries
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores