Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence

Vinícius Leite Pedro Bom, Patrícia Alves de Castro, Lizziane K Winkelströter, Marçal Marine, Juliana I Hori, Leandra Naira Zambelli Ramalho, Thaila Fernanda Dos Reis, Maria Helena S Goldman, Neil Andrew Brown, Ranjith Rajendran, Gordon Ramage, Louise A Walker, Carol A Munro, Marina Campos Rocha, Iran Malavazi, Daisuke Hagiwara, Gustavo H Goldman

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26 Citations (Scopus)

Abstract

Aspergillus fumigatus is an opportunistic pathogenic fungus able to infect immunocompromised patients, eventually causing disseminated infections that are difficult to control and lead to high mortality rates. It is important to understand how the signalling pathways that regulate these factors involved in virulence are orchestrated. Protein phosphatases are central to numerous signal transduction pathways. Here we characterize A. fumigatus protein phosphatase 2A SitA, the S. cerevisiae Sit4p homologue. The sitA gene is not an essential gene and we were able to construct an A. fumigatus null mutant. The ΔsitA strain had decreased MpkA phosphorylation levels, was more sensitive to cell wall damaging agents, had increased β-1,3-glucan and chitin, was impaired in biofilm formation, and had decreased protein kinase C activity. The ΔsitA strain is more sensitive to several metals and ions such as MnCl2, CaCl2, and LiCl, however, it is more resistant to ZnSO4. The ΔsitA strain was avirulent in a murine model of invasive pulmonary aspergillosis and induces an augmented TNF-α response in mouse macrophages. These results stress the importance of A. fumigatus SitA as a possible modulator of PkcA/MpkA activity and its involvement in the cell wall integrity pathway.

Original languageEnglish
Pages (from-to)728-744
Number of pages17
JournalEukaryotic Cell
Volume14
Issue number8
Early online date24 Apr 2015
DOIs
Publication statusPublished - Aug 2015

Keywords

  • Aspergillus fumigatus
  • sitA
  • pathogenic fungus

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    Bom, V. L. P., de Castro, P. A., Winkelströter, L. K., Marine, M., Hori, J. I., Ramalho, L. N. Z., Dos Reis, T. F., Goldman, M. H. S., Brown, N. A., Rajendran, R., Ramage, G., Walker, L. A., Munro, C. A., Rocha, M. C., Malavazi, I., Hagiwara, D., & Goldman, G. H. (2015). Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence. Eukaryotic Cell, 14(8), 728-744. https://doi.org/10.1128/EC.00008-15