The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>

ABSTRACT Polysaccharides are key components of both the fungal cell wall and biofilm matrix. Despite having distinct assembly and regulation pathways, matrix exopolysaccharide and cell wall polysaccharides share common substrates and intermediates in their biosynthetic pathways. It is not clear, how...

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Autores principales:	Yuan Chen, Francois Le Mauff, Yan Wang, Ruiyang Lu, Donald C. Sheppard, Ling Lu, Shizhu Zhang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	polysaccharides biofilm cell wall fungal pathogen Aspergillus fumigatus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5defdb444c7b4839a856a4a1d4c16034
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spelling	oai:doaj.org-article:5defdb444c7b4839a856a4a1d4c160342021-11-15T15:55:43ZThe Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>10.1128/mBio.02329-202150-7511https://doaj.org/article/5defdb444c7b4839a856a4a1d4c160342020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02329-20https://doaj.org/toc/2150-7511ABSTRACT Polysaccharides are key components of both the fungal cell wall and biofilm matrix. Despite having distinct assembly and regulation pathways, matrix exopolysaccharide and cell wall polysaccharides share common substrates and intermediates in their biosynthetic pathways. It is not clear, however, if the biosynthetic pathways governing the production of these polysaccharides are cooperatively regulated. Here, we demonstrate that cell wall stress promotes production of the exopolysaccharide galactosaminogalactan (GAG)-depend biofilm formation in the major fungal pathogen of humans Aspergillus fumigatus and that the transcription factor SomA plays a crucial role in mediating this process. A core set of SomA target genes were identified by transcriptome sequencing and chromatin immunoprecipitation coupled to sequencing (ChIP-Seq). We identified a novel SomA-binding site in the promoter regions of GAG biosynthetic genes agd3 and ega3, as well as its regulators medA and stuA. Strikingly, this SomA-binding site was also found in the upstream regions of genes encoding the cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Thus, SomA plays a direct regulation of both GAG and cell wall polysaccharide biosynthesis. Consistent with these findings, SomA is required for the maintenance of normal cell wall architecture and compositions in addition to its function in biofilm development. Moreover, SomA was found to globally regulate glucose uptake and utilization, as well as amino sugar and nucleotide sugar metabolism, which provides precursors for polysaccharide synthesis. Collectively, our work provides insight into fungal adaptive mechanisms in response to cell wall stress where biofilm formation and cell wall homeostasis were synchronously regulated. IMPORTANCE The cell wall is essential for fungal viability and is absent from human hosts; thus, drugs disrupting cell wall biosynthesis have gained more attention. Caspofungin is a member of a new class of clinically approved echinocandin drugs to treat invasive aspergillosis by blocking β-1,3-glucan synthase, thus damaging the fungal cell wall. Here, we demonstrate that caspofungin and other cell wall stressors can induce galactosaminogalactan (GAG)-dependent biofilm formation in the human pathogen Aspergillus fumigatus. We further identified SomA as a master transcription factor playing a dual role in both biofilm formation and cell wall homeostasis. SomA plays this dual role by direct binding to a conserved motif upstream of GAG biosynthetic genes and genes involved in cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Collectively, these findings reveal a transcriptional control pathway that integrates biofilm formation and cell wall homeostasis and suggest SomA as an attractive target for antifungal drug development.Yuan ChenFrancois Le MauffYan WangRuiyang LuDonald C. SheppardLing LuShizhu ZhangAmerican Society for Microbiologyarticlepolysaccharidesbiofilmcell wallfungal pathogenAspergillus fumigatusMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	polysaccharides biofilm cell wall fungal pathogen Aspergillus fumigatus Microbiology QR1-502
spellingShingle	polysaccharides biofilm cell wall fungal pathogen Aspergillus fumigatus Microbiology QR1-502 Yuan Chen Francois Le Mauff Yan Wang Ruiyang Lu Donald C. Sheppard Ling Lu Shizhu Zhang The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
description	ABSTRACT Polysaccharides are key components of both the fungal cell wall and biofilm matrix. Despite having distinct assembly and regulation pathways, matrix exopolysaccharide and cell wall polysaccharides share common substrates and intermediates in their biosynthetic pathways. It is not clear, however, if the biosynthetic pathways governing the production of these polysaccharides are cooperatively regulated. Here, we demonstrate that cell wall stress promotes production of the exopolysaccharide galactosaminogalactan (GAG)-depend biofilm formation in the major fungal pathogen of humans Aspergillus fumigatus and that the transcription factor SomA plays a crucial role in mediating this process. A core set of SomA target genes were identified by transcriptome sequencing and chromatin immunoprecipitation coupled to sequencing (ChIP-Seq). We identified a novel SomA-binding site in the promoter regions of GAG biosynthetic genes agd3 and ega3, as well as its regulators medA and stuA. Strikingly, this SomA-binding site was also found in the upstream regions of genes encoding the cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Thus, SomA plays a direct regulation of both GAG and cell wall polysaccharide biosynthesis. Consistent with these findings, SomA is required for the maintenance of normal cell wall architecture and compositions in addition to its function in biofilm development. Moreover, SomA was found to globally regulate glucose uptake and utilization, as well as amino sugar and nucleotide sugar metabolism, which provides precursors for polysaccharide synthesis. Collectively, our work provides insight into fungal adaptive mechanisms in response to cell wall stress where biofilm formation and cell wall homeostasis were synchronously regulated. IMPORTANCE The cell wall is essential for fungal viability and is absent from human hosts; thus, drugs disrupting cell wall biosynthesis have gained more attention. Caspofungin is a member of a new class of clinically approved echinocandin drugs to treat invasive aspergillosis by blocking β-1,3-glucan synthase, thus damaging the fungal cell wall. Here, we demonstrate that caspofungin and other cell wall stressors can induce galactosaminogalactan (GAG)-dependent biofilm formation in the human pathogen Aspergillus fumigatus. We further identified SomA as a master transcription factor playing a dual role in both biofilm formation and cell wall homeostasis. SomA plays this dual role by direct binding to a conserved motif upstream of GAG biosynthetic genes and genes involved in cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Collectively, these findings reveal a transcriptional control pathway that integrates biofilm formation and cell wall homeostasis and suggest SomA as an attractive target for antifungal drug development.
format	article
author	Yuan Chen Francois Le Mauff Yan Wang Ruiyang Lu Donald C. Sheppard Ling Lu Shizhu Zhang
author_facet	Yuan Chen Francois Le Mauff Yan Wang Ruiyang Lu Donald C. Sheppard Ling Lu Shizhu Zhang
author_sort	Yuan Chen
title	The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
title_short	The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
title_full	The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
title_fullStr	The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
title_full_unstemmed	The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>
title_sort	transcription factor soma synchronously regulates biofilm formation and cell wall homeostasis in <italic toggle="yes">aspergillus fumigatus</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5defdb444c7b4839a856a4a1d4c16034
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The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in <italic toggle="yes">Aspergillus fumigatus</italic>

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