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The Aspergillus fumigatus pkcA (G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model
Aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In A. fumigatus this signaling cascade is partially characterized,...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546635/ https://www.ncbi.nlm.nih.gov/pubmed/26295576 http://dx.doi.org/10.1371/journal.pone.0135195 |
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author | Rocha, Marina Campos de Godoy, Krissia Franco de Castro, Patrícia Alves Hori, Juliana Issa Bom, Vinícius Leite Pedro Brown, Neil Andrew da Cunha, Anderson Ferreira Goldman, Gustavo Henrique Malavazi, Iran |
author_facet | Rocha, Marina Campos de Godoy, Krissia Franco de Castro, Patrícia Alves Hori, Juliana Issa Bom, Vinícius Leite Pedro Brown, Neil Andrew da Cunha, Anderson Ferreira Goldman, Gustavo Henrique Malavazi, Iran |
author_sort | Rocha, Marina Campos |
collection | PubMed |
description | Aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In A. fumigatus this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. In this study we investigated the role of protein kinase C (PkcA) in this signaling cascade. Our results suggest that pkcA is an essential gene and is activated in response to cell wall stress. Subsequently, we constructed and analyzed a non-essential A. fumigatus pkcA (G579R) mutant, carrying a Gly579Arg substitution in the PkcA C1B regulatory domain. The pkcA (G579R) mutation has a reduced activation of the downstream Mitogen-Activated Protein Kinase, MpkA, resulting in the altered expression of genes encoding cell wall-related proteins, markers of endoplasmic reticulum stress and the unfolded protein response. Furthermore, PkcA(G579R) is involved in the formation of proper conidial architecture and protection to oxidative damage. The pkcA (G579R) mutant elicits increased production of TNF-α and phagocytosis but it has no impact on virulence in a murine model of invasive pulmonary aspergillosis. These results highlight the importance of PkcA to the CWI pathway but also indicated that additional regulatory circuits may be involved in the biosynthesis and/or reinforcement of the A. fumigatus cell wall during infection. |
format | Online Article Text |
id | pubmed-4546635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45466352015-09-01 The Aspergillus fumigatus pkcA (G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model Rocha, Marina Campos de Godoy, Krissia Franco de Castro, Patrícia Alves Hori, Juliana Issa Bom, Vinícius Leite Pedro Brown, Neil Andrew da Cunha, Anderson Ferreira Goldman, Gustavo Henrique Malavazi, Iran PLoS One Research Article Aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In A. fumigatus this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. In this study we investigated the role of protein kinase C (PkcA) in this signaling cascade. Our results suggest that pkcA is an essential gene and is activated in response to cell wall stress. Subsequently, we constructed and analyzed a non-essential A. fumigatus pkcA (G579R) mutant, carrying a Gly579Arg substitution in the PkcA C1B regulatory domain. The pkcA (G579R) mutation has a reduced activation of the downstream Mitogen-Activated Protein Kinase, MpkA, resulting in the altered expression of genes encoding cell wall-related proteins, markers of endoplasmic reticulum stress and the unfolded protein response. Furthermore, PkcA(G579R) is involved in the formation of proper conidial architecture and protection to oxidative damage. The pkcA (G579R) mutant elicits increased production of TNF-α and phagocytosis but it has no impact on virulence in a murine model of invasive pulmonary aspergillosis. These results highlight the importance of PkcA to the CWI pathway but also indicated that additional regulatory circuits may be involved in the biosynthesis and/or reinforcement of the A. fumigatus cell wall during infection. Public Library of Science 2015-08-21 /pmc/articles/PMC4546635/ /pubmed/26295576 http://dx.doi.org/10.1371/journal.pone.0135195 Text en © 2015 Rocha et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rocha, Marina Campos de Godoy, Krissia Franco de Castro, Patrícia Alves Hori, Juliana Issa Bom, Vinícius Leite Pedro Brown, Neil Andrew da Cunha, Anderson Ferreira Goldman, Gustavo Henrique Malavazi, Iran The Aspergillus fumigatus pkcA (G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title | The Aspergillus fumigatus pkcA
(G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title_full | The Aspergillus fumigatus pkcA
(G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title_fullStr | The Aspergillus fumigatus pkcA
(G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title_full_unstemmed | The Aspergillus fumigatus pkcA
(G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title_short | The Aspergillus fumigatus pkcA
(G579R) Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model |
title_sort | aspergillus fumigatus pkca
(g579r) mutant is defective in the activation of the cell wall integrity pathway but is dispensable for virulence in a neutropenic mouse infection model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546635/ https://www.ncbi.nlm.nih.gov/pubmed/26295576 http://dx.doi.org/10.1371/journal.pone.0135195 |
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