The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System

ABSTRACT Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsibl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Isabella Luísa da Silva Gurgel, Karina Talita de Oliveira Santana Jorge, Nathália Luísa Sousa de Oliveira Malacco, Jéssica Amanda Marques Souza, Marina Campos Rocha, Marina Faria Fernandes, Flávia Rayssa Braga Martins, Iran Malavazi, Mauro Martins Teixeira, Frederico Marianetti Soriani
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Aspergillus fumigatus cell wall integrity immune response msb2 mucin virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3fa619b008c643f7a1125801125eb32a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3fa619b008c643f7a1125801125eb32a
record_format	dspace
spelling	oai:doaj.org-article:3fa619b008c643f7a1125801125eb32a2021-11-15T15:22:20ZThe <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System10.1128/mSphere.00350-192379-5042https://doaj.org/article/3fa619b008c643f7a1125801125eb32a2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00350-19https://doaj.org/toc/2379-5042ABSTRACT Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsible for activation of a variety of mitogen-activated protein kinase (MAPK)-dependent signaling pathways that regulate cell growth in several organisms, such as the cell wall integrity (CWI) pathway. Here, we aimed to characterize the MSB2 homologue in A. fumigatus. Our results showed that MsbA plays a role in the vegetative and reproductive development of the fungus, in stress adaptation, and in resistance to antifungal drugs by modulating the CWI pathway gene expression. Importantly, cell wall composition is also responsible for activation of diverse receptors of the host immune system, thus leading to a proper immune response. In a model of acute Aspergillus pulmonary infection, results demonstrate that the ΔmsbA mutant strain induced less inflammation with diminished cell influx into the lungs and lower cytokine production, culminating in increased lethality rate. These results characterize for the first time the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis and an important regulator of virulence. IMPORTANCE Aspergillus fumigatus is an opportunistic fungus with great medical importance. During infection, Aspergillus grows, forming hyphae that colonize the lung tissue and invade and spread over the mammal host, resulting in high mortality rates. The knowledge of the mechanisms responsible for regulation of fungal growth and virulence comprises an important point to better understand fungal physiology and host-pathogen interactions. Msb2 is a mucin that acts as a sensor and an upstream regulator of the MAPK pathway responsible for fungal development in Candida albicans and Aspergillus nidulans. Here, we show the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis, fungal growth, and virulence. Moreover, we show that cell wall composition, controlled by MsbA, is detrimental for fungal recognition and clearance by immune cells. Our findings are important for the understanding of how fungal sensors modulate cell physiology.Isabella Luísa da Silva GurgelKarina Talita de Oliveira Santana JorgeNathália Luísa Sousa de Oliveira MalaccoJéssica Amanda Marques SouzaMarina Campos RochaMarina Faria FernandesFlávia Rayssa Braga MartinsIran MalavaziMauro Martins TeixeiraFrederico Marianetti SorianiAmerican Society for MicrobiologyarticleAspergillus fumigatuscell wall integrityimmune responsemsb2mucinvirulenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus cell wall integrity immune response msb2 mucin virulence Microbiology QR1-502
spellingShingle	Aspergillus fumigatus cell wall integrity immune response msb2 mucin virulence Microbiology QR1-502 Isabella Luísa da Silva Gurgel Karina Talita de Oliveira Santana Jorge Nathália Luísa Sousa de Oliveira Malacco Jéssica Amanda Marques Souza Marina Campos Rocha Marina Faria Fernandes Flávia Rayssa Braga Martins Iran Malavazi Mauro Martins Teixeira Frederico Marianetti Soriani The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
description	ABSTRACT Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsible for activation of a variety of mitogen-activated protein kinase (MAPK)-dependent signaling pathways that regulate cell growth in several organisms, such as the cell wall integrity (CWI) pathway. Here, we aimed to characterize the MSB2 homologue in A. fumigatus. Our results showed that MsbA plays a role in the vegetative and reproductive development of the fungus, in stress adaptation, and in resistance to antifungal drugs by modulating the CWI pathway gene expression. Importantly, cell wall composition is also responsible for activation of diverse receptors of the host immune system, thus leading to a proper immune response. In a model of acute Aspergillus pulmonary infection, results demonstrate that the ΔmsbA mutant strain induced less inflammation with diminished cell influx into the lungs and lower cytokine production, culminating in increased lethality rate. These results characterize for the first time the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis and an important regulator of virulence. IMPORTANCE Aspergillus fumigatus is an opportunistic fungus with great medical importance. During infection, Aspergillus grows, forming hyphae that colonize the lung tissue and invade and spread over the mammal host, resulting in high mortality rates. The knowledge of the mechanisms responsible for regulation of fungal growth and virulence comprises an important point to better understand fungal physiology and host-pathogen interactions. Msb2 is a mucin that acts as a sensor and an upstream regulator of the MAPK pathway responsible for fungal development in Candida albicans and Aspergillus nidulans. Here, we show the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis, fungal growth, and virulence. Moreover, we show that cell wall composition, controlled by MsbA, is detrimental for fungal recognition and clearance by immune cells. Our findings are important for the understanding of how fungal sensors modulate cell physiology.
format	article
author	Isabella Luísa da Silva Gurgel Karina Talita de Oliveira Santana Jorge Nathália Luísa Sousa de Oliveira Malacco Jéssica Amanda Marques Souza Marina Campos Rocha Marina Faria Fernandes Flávia Rayssa Braga Martins Iran Malavazi Mauro Martins Teixeira Frederico Marianetti Soriani
author_facet	Isabella Luísa da Silva Gurgel Karina Talita de Oliveira Santana Jorge Nathália Luísa Sousa de Oliveira Malacco Jéssica Amanda Marques Souza Marina Campos Rocha Marina Faria Fernandes Flávia Rayssa Braga Martins Iran Malavazi Mauro Martins Teixeira Frederico Marianetti Soriani
author_sort	Isabella Luísa da Silva Gurgel
title	The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
title_short	The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
title_full	The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
title_fullStr	The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
title_full_unstemmed	The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System
title_sort	<italic toggle="yes">aspergillus fumigatus</italic> mucin msba regulates the cell wall integrity pathway and controls recognition of the fungus by the immune system
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/3fa619b008c643f7a1125801125eb32a
work_keys_str_mv	AT isabellaluisadasilvagurgel theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT karinatalitadeoliveirasantanajorge theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT nathalialuisasousadeoliveiramalacco theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT jessicaamandamarquessouza theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT marinacamposrocha theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT marinafariafernandes theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT flaviarayssabragamartins theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT iranmalavazi theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT mauromartinsteixeira theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT fredericomarianettisoriani theitalictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT isabellaluisadasilvagurgel italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT karinatalitadeoliveirasantanajorge italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT nathalialuisasousadeoliveiramalacco italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT jessicaamandamarquessouza italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT marinacamposrocha italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT marinafariafernandes italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT flaviarayssabragamartins italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT iranmalavazi italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT mauromartinsteixeira italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem AT fredericomarianettisoriani italictoggleyesaspergillusfumigatusitalicmucinmsbaregulatesthecellwallintegritypathwayandcontrolsrecognitionofthefungusbytheimmunesystem
_version_	1718428004083826688

The <italic toggle="yes">Aspergillus fumigatus</italic> Mucin MsbA Regulates the Cell Wall Integrity Pathway and Controls Recognition of the Fungus by the Immune System

Ejemplares similares