Mitogen activated kinases (MAPK) and protein phosphatases are involved in Aspergillus fumigatus adhesion and biofilm formation

Adriana Manfiolli, Thaila Fernanda Dos Reis, Leandro José de Assis, Patrícia Alves de Castro, Lilian Pereira Silva, Juliana Hori, Louise A Walker, Carol A Munro, Ranjith Rajendran, Gordon Ramage, Gustavo H Goldman (Corresponding Author)

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Abstract

The main characteristic of biofilm formation is extracellular matrix (ECM) production. The cells within the biofilm are surrounded by ECM which provides structural integrity and protection. During an infection, this protection is mainly against cells of the immune system and antifungal drugs. A. fumigatus forms biofilms during static growth on a solid substratum and in chronic aspergillosis infections. It is important to understand how, and which, A. fumigatus signal transduction pathways are important for the adhesion and biofilm formation in a host during infection. Here we investigated the role of MAP kinases and protein phosphatases in biofilm formation. The loss of the MAP kinases MpkA, MpkC and SakA had an impact on the cell surface and the ECM during biofilm formation and reduced the adherence of A. fumigatus to polystyrene and fibronectin-coated plates. The phosphatase null mutants ΔsitA and ΔptcB, involved in regulation of MpkA and SakA phosphorylation, influenced cell wall carbohydrate exposure. Moreover, we characterized the A. fumigatus protein phosphatase PphA. The ΔpphA strain was more sensitive to cell wall-damaging agents, had increased β-(1,3)-glucan and reduced chitin, decreased conidia phagocytosis by Dictyostelium discoideum and reduced adhesion and biofilm formation. Finally, ΔpphA strain was avirulent in a murine model of invasive pulmonary aspergillosis and increased the released of tumor necrosis factor alpha (TNF-α) from bone marrow derived macrophages (BMDMs). These results show that MAP kinases and phosphatases play an important role in signaling pathways that regulate the composition of the cell wall, extracellular matrix production as well as adhesion and biofilm formation in A. fumigatus.
Original languageEnglish
Pages (from-to)43-56
Number of pages14
JournalThe Cell Surface
Volume1
Early online date26 Mar 2018
DOIs
Publication statusPublished - Mar 2018

Keywords

  • aspergillus fumigatus
  • polysaccharide
  • extracellular matrix
  • biofilm
  • mitogen activated kinases
  • phosphatases

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    Manfiolli, A., Dos Reis, T. F., de Assis, L. J., de Castro, P. A., Pereira Silva, L., Hori, J., Walker, L. A., Munro, C. A., Rajendran, R., Ramage, G., & Goldman, G. H. (2018). Mitogen activated kinases (MAPK) and protein phosphatases are involved in Aspergillus fumigatus adhesion and biofilm formation. The Cell Surface, 1, 43-56. https://doi.org/10.1016/j.tcsw.2018.03.002