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Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus

Aspergillus fumigatus causes most of aspergillosis in clinic and comprehensive function analysis of its key protein would promote anti-aspergillosis. In a previous study, we speculated actin depolymerizing factor cofilin might be essential for A. fumigatus viability and found its overexpression upre...

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Autores principales: Jia, Xiaodong, Zhang, Xi, Hu, Yingsong, Hu, Mandong, Han, Xuelin, Sun, Yansong, Han, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230985/
https://www.ncbi.nlm.nih.gov/pubmed/30455681
http://dx.doi.org/10.3389/fmicb.2018.02667
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author Jia, Xiaodong
Zhang, Xi
Hu, Yingsong
Hu, Mandong
Han, Xuelin
Sun, Yansong
Han, Li
author_facet Jia, Xiaodong
Zhang, Xi
Hu, Yingsong
Hu, Mandong
Han, Xuelin
Sun, Yansong
Han, Li
author_sort Jia, Xiaodong
collection PubMed
description Aspergillus fumigatus causes most of aspergillosis in clinic and comprehensive function analysis of its key protein would promote anti-aspergillosis. In a previous study, we speculated actin depolymerizing factor cofilin might be essential for A. fumigatus viability and found its overexpression upregulated oxidative response and cell wall polysaccharide synthesis of this pathogen. Here, we constructed a conditional cofilin mutant to determine the essential role of cofilin. And the role of cofilin downregulation and phosphorylation in A. fumigatus was further analyzed. Cofilin was required for the polarized growth and heat sensitivity of A. fumigatus. Downregulation of cofilin caused hyphal cytoplasmic leakage, increased the sensitivity of A. fumigatus to sodium dodecyl sulfonate but not to calcofluor white and Congo Red and farnesol, and enhanced the basal phosphorylation level of MpkA, suggesting that cofilin affected the cell wall integrity (CWI) signaling. Downregulation of cofilin also increased the sensitivity of A. fumigatus to alkaline pH and H(2)O(2). Repressing cofilin expression in A. fumigatus lead to attenuated virulence, which manifested as lower adherence and internalization rates, weaker host inflammatory response and shorter survival rate in a Galleria mellonella model. Expression of non-phosphorylated cofilin with a mutation of S5A had little impacts on A. fumigatus, whereas expression of a mimic-phosphorylated cofilin with a mutation of S5E resulted in inhibited growth, increased phospho-MpkA level, and decreased pathogenicity. In conclusion, cofilin is crucial to modulating the polarized growth, stress response, CWI and virulence of A. fumigatus.
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spelling pubmed-62309852018-11-19 Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus Jia, Xiaodong Zhang, Xi Hu, Yingsong Hu, Mandong Han, Xuelin Sun, Yansong Han, Li Front Microbiol Microbiology Aspergillus fumigatus causes most of aspergillosis in clinic and comprehensive function analysis of its key protein would promote anti-aspergillosis. In a previous study, we speculated actin depolymerizing factor cofilin might be essential for A. fumigatus viability and found its overexpression upregulated oxidative response and cell wall polysaccharide synthesis of this pathogen. Here, we constructed a conditional cofilin mutant to determine the essential role of cofilin. And the role of cofilin downregulation and phosphorylation in A. fumigatus was further analyzed. Cofilin was required for the polarized growth and heat sensitivity of A. fumigatus. Downregulation of cofilin caused hyphal cytoplasmic leakage, increased the sensitivity of A. fumigatus to sodium dodecyl sulfonate but not to calcofluor white and Congo Red and farnesol, and enhanced the basal phosphorylation level of MpkA, suggesting that cofilin affected the cell wall integrity (CWI) signaling. Downregulation of cofilin also increased the sensitivity of A. fumigatus to alkaline pH and H(2)O(2). Repressing cofilin expression in A. fumigatus lead to attenuated virulence, which manifested as lower adherence and internalization rates, weaker host inflammatory response and shorter survival rate in a Galleria mellonella model. Expression of non-phosphorylated cofilin with a mutation of S5A had little impacts on A. fumigatus, whereas expression of a mimic-phosphorylated cofilin with a mutation of S5E resulted in inhibited growth, increased phospho-MpkA level, and decreased pathogenicity. In conclusion, cofilin is crucial to modulating the polarized growth, stress response, CWI and virulence of A. fumigatus. Frontiers Media S.A. 2018-11-02 /pmc/articles/PMC6230985/ /pubmed/30455681 http://dx.doi.org/10.3389/fmicb.2018.02667 Text en Copyright © 2018 Jia, Zhang, Hu, Hu, Han, Sun and Han. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Jia, Xiaodong
Zhang, Xi
Hu, Yingsong
Hu, Mandong
Han, Xuelin
Sun, Yansong
Han, Li
Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title_full Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title_fullStr Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title_full_unstemmed Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title_short Role of Downregulation and Phosphorylation of Cofilin in Polarized Growth, MpkA Activation and Stress Response of Aspergillus fumigatus
title_sort role of downregulation and phosphorylation of cofilin in polarized growth, mpka activation and stress response of aspergillus fumigatus
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230985/
https://www.ncbi.nlm.nih.gov/pubmed/30455681
http://dx.doi.org/10.3389/fmicb.2018.02667
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