Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>

ABSTRACT Aspergillus fumigatus mitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage com...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Leandro José de Assis, Adriana Manfiolli, Eliciane Mattos, João H. T. Marilhano Fabri, Iran Malavazi, Ilse D. Jacobsen, Matthias Brock, Robert A. Cramer, Arsa Thammahong, Daisuke Hagiwara, Laure Nicolas Annick Ries, Gustavo Henrique Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Aspergillus fumigatus cell wall glycogen high-osmotic glycerol pathway protein kinase A trehalose Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3aef535fc0a64151ad7811eec055334e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3aef535fc0a64151ad7811eec055334e
record_format	dspace
spelling	oai:doaj.org-article:3aef535fc0a64151ad7811eec055334e2021-11-15T15:52:19ZProtein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>10.1128/mBio.01952-182150-7511https://doaj.org/article/3aef535fc0a64151ad7811eec055334e2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01952-18https://doaj.org/toc/2150-7511ABSTRACT Aspergillus fumigatus mitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage compounds. Here we show that this process is dependent on cAMP-dependent protein kinase A (PKA) activity and regulated by the high-osmolarity glycerol response (HOG) MAPKs SakA and MpkC. These protein kinases are necessary for normal accumulation/degradation of trehalose and glycogen, and the lack of these genes reduces glucose uptake and glycogen synthesis. Alterations in glycogen synthesis were observed for the sakA and mpkC deletion mutants, which also displayed alterations in carbohydrate exposure on the cell wall. Carbohydrate mobilization is controlled by SakA interaction with PkaC1 and PkaR, suggesting a putative mechanism where the PkaR regulatory subunit leaves the complex and releases the SakA-PkaC1 complex for activation of enzymes involved in carbohydrate mobilization. This work reveals the communication between the HOG and PKA pathways for carbohydrate mobilization for cell wall construction. IMPORTANCE Aspergillus fumigatus is an opportunistic human pathogen causing allergic reactions or systemic infections such as invasive pulmonary aspergillosis, especially in immunocompromised patients. The fungal cell wall is the main component responsible for recognition by the immune system, due to the specific composition of polysaccharide carbohydrates exposed on the surface of the fungal cell wall called pathogen-associated molecular patterns (PAMPs). Key enzymes in the fungal cell wall biosynthesis are a good target for fungal drug development. This report elucidates the cooperation between the HOG and PKA pathways in the mobilization of carbohydrates for fungal cell wall biosynthesis. We suggest that the reduced mobilization of simple sugars causes defects in the structure of the fungal cell wall. In summary, we propose that SakA is important for PKA activity, therefore regulating the availability and mobilization of monosaccharides for fungal cell wall biosynthesis during cell wall damage and the osmotic stress response.Leandro José de AssisAdriana ManfiolliEliciane MattosJoão H. T. Marilhano FabriIran MalavaziIlse D. JacobsenMatthias BrockRobert A. CramerArsa ThammahongDaisuke HagiwaraLaure Nicolas Annick RiesGustavo Henrique GoldmanAmerican Society for MicrobiologyarticleAspergillus fumigatuscell wallglycogenhigh-osmotic glycerol pathwayprotein kinase AtrehaloseMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus cell wall glycogen high-osmotic glycerol pathway protein kinase A trehalose Microbiology QR1-502
spellingShingle	Aspergillus fumigatus cell wall glycogen high-osmotic glycerol pathway protein kinase A trehalose Microbiology QR1-502 Leandro José de Assis Adriana Manfiolli Eliciane Mattos João H. T. Marilhano Fabri Iran Malavazi Ilse D. Jacobsen Matthias Brock Robert A. Cramer Arsa Thammahong Daisuke Hagiwara Laure Nicolas Annick Ries Gustavo Henrique Goldman Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
description	ABSTRACT Aspergillus fumigatus mitogen-activated protein kinases (MAPKs) are involved in maintaining the normal morphology of the cell wall and providing resistance against cell wall-damaging agents. Upon cell wall stress, cell wall-related sugars need to be synthesized from carbohydrate storage compounds. Here we show that this process is dependent on cAMP-dependent protein kinase A (PKA) activity and regulated by the high-osmolarity glycerol response (HOG) MAPKs SakA and MpkC. These protein kinases are necessary for normal accumulation/degradation of trehalose and glycogen, and the lack of these genes reduces glucose uptake and glycogen synthesis. Alterations in glycogen synthesis were observed for the sakA and mpkC deletion mutants, which also displayed alterations in carbohydrate exposure on the cell wall. Carbohydrate mobilization is controlled by SakA interaction with PkaC1 and PkaR, suggesting a putative mechanism where the PkaR regulatory subunit leaves the complex and releases the SakA-PkaC1 complex for activation of enzymes involved in carbohydrate mobilization. This work reveals the communication between the HOG and PKA pathways for carbohydrate mobilization for cell wall construction. IMPORTANCE Aspergillus fumigatus is an opportunistic human pathogen causing allergic reactions or systemic infections such as invasive pulmonary aspergillosis, especially in immunocompromised patients. The fungal cell wall is the main component responsible for recognition by the immune system, due to the specific composition of polysaccharide carbohydrates exposed on the surface of the fungal cell wall called pathogen-associated molecular patterns (PAMPs). Key enzymes in the fungal cell wall biosynthesis are a good target for fungal drug development. This report elucidates the cooperation between the HOG and PKA pathways in the mobilization of carbohydrates for fungal cell wall biosynthesis. We suggest that the reduced mobilization of simple sugars causes defects in the structure of the fungal cell wall. In summary, we propose that SakA is important for PKA activity, therefore regulating the availability and mobilization of monosaccharides for fungal cell wall biosynthesis during cell wall damage and the osmotic stress response.
format	article
author	Leandro José de Assis Adriana Manfiolli Eliciane Mattos João H. T. Marilhano Fabri Iran Malavazi Ilse D. Jacobsen Matthias Brock Robert A. Cramer Arsa Thammahong Daisuke Hagiwara Laure Nicolas Annick Ries Gustavo Henrique Goldman
author_facet	Leandro José de Assis Adriana Manfiolli Eliciane Mattos João H. T. Marilhano Fabri Iran Malavazi Ilse D. Jacobsen Matthias Brock Robert A. Cramer Arsa Thammahong Daisuke Hagiwara Laure Nicolas Annick Ries Gustavo Henrique Goldman
author_sort	Leandro José de Assis
title	Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
title_short	Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
title_full	Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
title_fullStr	Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
title_full_unstemmed	Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>
title_sort	protein kinase a and high-osmolarity glycerol response pathways cooperatively control cell wall carbohydrate mobilization in <italic toggle="yes">aspergillus fumigatus</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/3aef535fc0a64151ad7811eec055334e
work_keys_str_mv	AT leandrojosedeassis proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT adrianamanfiolli proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT elicianemattos proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT joaohtmarilhanofabri proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT iranmalavazi proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT ilsedjacobsen proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT matthiasbrock proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT robertacramer proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT arsathammahong proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT daisukehagiwara proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT laurenicolasannickries proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic AT gustavohenriquegoldman proteinkinaseaandhighosmolarityglycerolresponsepathwayscooperativelycontrolcellwallcarbohydratemobilizationinitalictoggleyesaspergillusfumigatusitalic
_version_	1718427268791926784

Protein Kinase A and High-Osmolarity Glycerol Response Pathways Cooperatively Control Cell Wall Carbohydrate Mobilization in <italic toggle="yes">Aspergillus fumigatus</italic>

Ejemplares similares