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

Research output: Contribution to journalArticle

19 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

Fingerprint

Aspergillus fumigatus
Biofilms
Phosphoric Monoester Hydrolases
Cell Wall
Virulence
Invasive Pulmonary Aspergillosis
Protein Phosphatase 2
Chitin
Glucans
Phosphoprotein Phosphatases
Essential Genes
Immunocompromised Host
Protein Kinase C
Saccharomyces cerevisiae
Signal Transduction
Fungi
Metals
Macrophages
Phosphorylation
Ions

Keywords

  • Aspergillus fumigatus
  • sitA
  • pathogenic fungus

Cite this

Bom, V. L. P., de Castro, P. A., Winkelströter, L. K., Marine, M., Hori, J. I., Ramalho, L. N. Z., ... 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

Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence. / Bom, Vinícius Leite Pedro; de Castro, Patrícia Alves; Winkelströter, Lizziane K; Marine, Marçal; Hori, Juliana I; Ramalho, Leandra Naira Zambelli; Dos Reis, Thaila Fernanda; Goldman, Maria Helena S; Brown, Neil Andrew; Rajendran, Ranjith; Ramage, Gordon; Walker, Louise A; Munro, Carol A; Rocha, Marina Campos; Malavazi, Iran; Hagiwara, Daisuke; Goldman, Gustavo H.

In: Eukaryotic Cell, Vol. 14, No. 8, 08.2015, p. 728-744.

Research output: Contribution to journalArticle

Bom, VLP, de Castro, PA, Winkelströter, LK, Marine, M, Hori, JI, Ramalho, LNZ, Dos Reis, TF, Goldman, MHS, Brown, NA, Rajendran, R, Ramage, G, Walker, LA, Munro, CA, Rocha, MC, Malavazi, I, Hagiwara, D & Goldman, GH 2015, 'Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence', Eukaryotic Cell, vol. 14, no. 8, pp. 728-744. https://doi.org/10.1128/EC.00008-15
Bom, Vinícius Leite Pedro ; de Castro, Patrícia Alves ; Winkelströter, Lizziane K ; Marine, Marçal ; Hori, Juliana I ; Ramalho, Leandra Naira Zambelli ; Dos Reis, Thaila Fernanda ; Goldman, Maria Helena S ; Brown, Neil Andrew ; Rajendran, Ranjith ; Ramage, Gordon ; Walker, Louise A ; Munro, Carol A ; Rocha, Marina Campos ; Malavazi, Iran ; Hagiwara, Daisuke ; Goldman, Gustavo H. / Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence. In: Eukaryotic Cell. 2015 ; Vol. 14, No. 8. pp. 728-744.
@article{dfc71bde726d438696151e25c216a11d,
title = "Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence",
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.",
keywords = "Aspergillus fumigatus, sitA, pathogenic fungus",
author = "Bom, {Vin{\'i}cius Leite Pedro} and {de Castro}, {Patr{\'i}cia Alves} and Winkelstr{\"o}ter, {Lizziane K} and Mar{\cc}al Marine and Hori, {Juliana I} and Ramalho, {Leandra Naira Zambelli} and {Dos Reis}, {Thaila Fernanda} and Goldman, {Maria Helena S} and Brown, {Neil Andrew} and Ranjith Rajendran and Gordon Ramage and Walker, {Louise A} and Munro, {Carol A} and Rocha, {Marina Campos} and Iran Malavazi and Daisuke Hagiwara and Goldman, {Gustavo H}",
note = "Copyright {\circledC} 2015, American Society for Microbiology. All Rights Reserved.",
year = "2015",
month = "8",
doi = "10.1128/EC.00008-15",
language = "English",
volume = "14",
pages = "728--744",
journal = "Eukaryotic Cell",
issn = "1535-9778",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Aspergillus fumigatus sitA phosphatase homologue is important for adhesion, cell wall integrity, biofilm formation and virulence

AU - Bom, Vinícius Leite Pedro

AU - de Castro, Patrícia Alves

AU - Winkelströter, Lizziane K

AU - Marine, Marçal

AU - Hori, Juliana I

AU - Ramalho, Leandra Naira Zambelli

AU - Dos Reis, Thaila Fernanda

AU - Goldman, Maria Helena S

AU - Brown, Neil Andrew

AU - Rajendran, Ranjith

AU - Ramage, Gordon

AU - Walker, Louise A

AU - Munro, Carol A

AU - Rocha, Marina Campos

AU - Malavazi, Iran

AU - Hagiwara, Daisuke

AU - Goldman, Gustavo H

N1 - Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

KW - Aspergillus fumigatus

KW - sitA

KW - pathogenic fungus

U2 - 10.1128/EC.00008-15

DO - 10.1128/EC.00008-15

M3 - Article

VL - 14

SP - 728

EP - 744

JO - Eukaryotic Cell

JF - Eukaryotic Cell

SN - 1535-9778

IS - 8

ER -