HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.

Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of the ER becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt ER homeostasis. In yeast and other fungi, the accumulation of unfolded proteins is detected by the ER-tra...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xizhi Feng, Karthik Krishnan, Daryl L Richie, Vishukumar Aimanianda, Lukas Hartl, Nora Grahl, Margaret V Powers-Fletcher, Minlu Zhang, Kevin K Fuller, William C Nierman, Long Jason Lu, Jean-Paul Latgé, Laura Woollett, Simon L Newman, Robert A Cramer, Judith C Rhodes, David S Askew
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e8921120d708438bbfb7eba100185cce
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e8921120d708438bbfb7eba100185cce
record_format	dspace
spelling	oai:doaj.org-article:e8921120d708438bbfb7eba100185cce2021-11-18T06:05:13ZHacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.1553-73661553-737410.1371/journal.ppat.1002330https://doaj.org/article/e8921120d708438bbfb7eba100185cce2011-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028661/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of the ER becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt ER homeostasis. In yeast and other fungi, the accumulation of unfolded proteins is detected by the ER-transmembrane sensor IreA/Ire1, which responds by cleaving an intron from the downstream cytoplasmic mRNA HacA/Hac1, allowing for the translation of a transcription factor that coordinates a series of adaptive responses that are collectively known as the unfolded protein response (UPR). Here, we examined the contribution of IreA to growth and virulence in the human fungal pathogen Aspergillus fumigatus. Gene expression profiling revealed that A. fumigatus IreA signals predominantly through the canonical IreA-HacA pathway under conditions of severe ER stress. However, in the absence of ER stress IreA controls dual signaling circuits that are both HacA-dependent and HacA-independent. We found that a ΔireA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasts the partial virulence of a ΔhacA mutant, suggesting that IreA contributes to pathogenesis independently of HacA. In support of this conclusion, we found that the ΔireA mutant had more severe defects in the expression of multiple virulence-related traits relative to ΔhacA, including reduced thermotolerance, decreased nutritional versatility, impaired growth under hypoxia, altered cell wall and membrane composition, and increased susceptibility to azole antifungals. In addition, full or partial virulence could be restored to the ΔireA mutant by complementation with either the induced form of the hacA mRNA, hacA(i), or an ireA deletion mutant that was incapable of processing the hacA mRNA, ireA(Δ10). Together, these findings demonstrate that IreA has both HacA-dependent and HacA-independent functions that contribute to the expression of traits that are essential for virulence in A. fumigatus.Xizhi FengKarthik KrishnanDaryl L RichieVishukumar AimaniandaLukas HartlNora GrahlMargaret V Powers-FletcherMinlu ZhangKevin K FullerWilliam C NiermanLong Jason LuJean-Paul LatgéLaura WoollettSimon L NewmanRobert A CramerJudith C RhodesDavid S AskewPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 10, p e1002330 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Xizhi Feng Karthik Krishnan Daryl L Richie Vishukumar Aimanianda Lukas Hartl Nora Grahl Margaret V Powers-Fletcher Minlu Zhang Kevin K Fuller William C Nierman Long Jason Lu Jean-Paul Latgé Laura Woollett Simon L Newman Robert A Cramer Judith C Rhodes David S Askew HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
description	Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of the ER becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt ER homeostasis. In yeast and other fungi, the accumulation of unfolded proteins is detected by the ER-transmembrane sensor IreA/Ire1, which responds by cleaving an intron from the downstream cytoplasmic mRNA HacA/Hac1, allowing for the translation of a transcription factor that coordinates a series of adaptive responses that are collectively known as the unfolded protein response (UPR). Here, we examined the contribution of IreA to growth and virulence in the human fungal pathogen Aspergillus fumigatus. Gene expression profiling revealed that A. fumigatus IreA signals predominantly through the canonical IreA-HacA pathway under conditions of severe ER stress. However, in the absence of ER stress IreA controls dual signaling circuits that are both HacA-dependent and HacA-independent. We found that a ΔireA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasts the partial virulence of a ΔhacA mutant, suggesting that IreA contributes to pathogenesis independently of HacA. In support of this conclusion, we found that the ΔireA mutant had more severe defects in the expression of multiple virulence-related traits relative to ΔhacA, including reduced thermotolerance, decreased nutritional versatility, impaired growth under hypoxia, altered cell wall and membrane composition, and increased susceptibility to azole antifungals. In addition, full or partial virulence could be restored to the ΔireA mutant by complementation with either the induced form of the hacA mRNA, hacA(i), or an ireA deletion mutant that was incapable of processing the hacA mRNA, ireA(Δ10). Together, these findings demonstrate that IreA has both HacA-dependent and HacA-independent functions that contribute to the expression of traits that are essential for virulence in A. fumigatus.
format	article
author	Xizhi Feng Karthik Krishnan Daryl L Richie Vishukumar Aimanianda Lukas Hartl Nora Grahl Margaret V Powers-Fletcher Minlu Zhang Kevin K Fuller William C Nierman Long Jason Lu Jean-Paul Latgé Laura Woollett Simon L Newman Robert A Cramer Judith C Rhodes David S Askew
author_facet	Xizhi Feng Karthik Krishnan Daryl L Richie Vishukumar Aimanianda Lukas Hartl Nora Grahl Margaret V Powers-Fletcher Minlu Zhang Kevin K Fuller William C Nierman Long Jason Lu Jean-Paul Latgé Laura Woollett Simon L Newman Robert A Cramer Judith C Rhodes David S Askew
author_sort	Xizhi Feng
title	HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
title_short	HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
title_full	HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
title_fullStr	HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
title_full_unstemmed	HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.
title_sort	haca-independent functions of the er stress sensor irea synergize with the canonical upr to influence virulence traits in aspergillus fumigatus.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/e8921120d708438bbfb7eba100185cce
work_keys_str_mv	AT xizhifeng hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT karthikkrishnan hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT daryllrichie hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT vishukumaraimanianda hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT lukashartl hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT noragrahl hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT margaretvpowersfletcher hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT minluzhang hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT kevinkfuller hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT williamcnierman hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT longjasonlu hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT jeanpaullatge hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT laurawoollett hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT simonlnewman hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT robertacramer hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT judithcrhodes hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus AT davidsaskew hacaindependentfunctionsoftheerstresssensorireasynergizewiththecanonicaluprtoinfluencevirulencetraitsinaspergillusfumigatus
_version_	1718424639151013888

HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus.

Ejemplares similares