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

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Mitogen-Activated Protein Kinase Phosphatases
Aspergillus fumigatus
Biofilms
Mitogen-Activated Protein Kinases
Extracellular Matrix
Cell Wall
Phosphotransferases
Phosphoprotein Phosphatases
Phosphoric Monoester Hydrolases
Infection
Invasive Pulmonary Aspergillosis
Dictyostelium
Chitin
Aspergillosis
Fungal Spores
Glucans
Polystyrenes
Fibronectins
Phagocytosis
Immune System

Keywords

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

Cite this

Manfiolli, A., Dos Reis, T. F., de Assis, L. J., de Castro, P. A., Pereira Silva, L., Hori, J., ... 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

Mitogen activated kinases (MAPK) and protein phosphatases are involved in Aspergillus fumigatus adhesion and biofilm formation. / Manfiolli, Adriana ; Dos Reis, Thaila Fernanda; de Assis, Leandro José ; de Castro, Patrícia Alves; Pereira Silva, Lilian ; Hori, Juliana; Walker, Louise A; Munro, Carol A; Rajendran, Ranjith; Ramage, Gordon; Goldman, Gustavo H (Corresponding Author).

In: The Cell Surface, Vol. 1, 03.2018, p. 43-56.

Research output: Contribution to journalArticle

Manfiolli, A, Dos Reis, TF, de Assis, LJ, de Castro, PA, Pereira Silva, L, Hori, J, Walker, LA, Munro, CA, Rajendran, R, Ramage, G & Goldman, GH 2018, 'Mitogen activated kinases (MAPK) and protein phosphatases are involved in Aspergillus fumigatus adhesion and biofilm formation', The Cell Surface, vol. 1, pp. 43-56. https://doi.org/10.1016/j.tcsw.2018.03.002
Manfiolli, Adriana ; Dos Reis, Thaila Fernanda ; de Assis, Leandro José ; de Castro, Patrícia Alves ; Pereira Silva, Lilian ; Hori, Juliana ; Walker, Louise A ; Munro, Carol A ; Rajendran, Ranjith ; Ramage, Gordon ; Goldman, Gustavo H. / Mitogen activated kinases (MAPK) and protein phosphatases are involved in Aspergillus fumigatus adhesion and biofilm formation. In: The Cell Surface. 2018 ; Vol. 1. pp. 43-56.
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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.",
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AU - de Assis, Leandro José

AU - de Castro, Patrícia Alves

AU - Pereira Silva, Lilian

AU - Hori, Juliana

AU - Walker, Louise A

AU - Munro, Carol A

AU - Rajendran, Ranjith

AU - Ramage, Gordon

AU - Goldman, Gustavo H

N1 - We would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for providing financial support. LW and CM would like to acknowledge support from the University of Aberdeen and the MRC Centre for Medical Mycology (MR/N006364/1). All authors declare no financial conflict of interest.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

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KW - aspergillus fumigatus

KW - polysaccharide

KW - extracellular matrix

KW - biofilm

KW - mitogen activated kinases

KW - phosphatases

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JO - The Cell Surface

JF - The Cell Surface

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