Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates

The ubiquitous filamentous fungus Aspergillus fumigatus secretes a number of allergens with protease activity and has been linked to a variety of allergic conditions such as Severe Asthma with Fungal Sensitization (SAFS) and Allergic Bronchopulmonary Aspergillosis (ABPA). However, it is unclear whic...

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Main Authors:	Farnell, Edward, Rousseau, Karine, Thornton, David J., Bowyer, Paul, Herrick, Sarah E.
Format:	Online
Language:	English
Published:	Published by Elsevier, copyright by British Mycological Society 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605576/

id	pubmed-3605576
recordtype	oai_dc
spelling	pubmed-36055762013-03-22 Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates Farnell, Edward Rousseau, Karine Thornton, David J. Bowyer, Paul Herrick, Sarah E. Article The ubiquitous filamentous fungus Aspergillus fumigatus secretes a number of allergens with protease activity and has been linked to a variety of allergic conditions such as Severe Asthma with Fungal Sensitization (SAFS) and Allergic Bronchopulmonary Aspergillosis (ABPA). However, it is unclear which allergen proteases are being secreted during fungal invasion and whether the local biological environment regulates their expression. Understanding the dynamic expression of allergen proteases during growth of A. fumigatus may lead to further characterisation of the pathogenesis of these disorders as well as improved standardisation in the commercial production of these allergens. Secretion of proteases during germination and early growth of A. fumigatus was investigated in response to various complex protein sources (pig lung homogenate, mucin or casein). Protease inhibitor studies demonstrated that A. fumigatus (AF293 strain) secretes predominately serine proteases during growth in pig lung based medium and mainly metalloproteases during growth in casein based medium but suppressed protease secretion in unmodified Vogel's minimal medium and secreted both types in mucin based medium. Analysis of gene transcription and protein identification by mass spectrometry showed that the matrix metalloprotease, Mep/Asp f 5 and the serine protease, Alp1/Asp f 13, were upregulated and secreted during growth in pig lung medium, whereas Alp1 was predominately expressed and secreted in mucin based medium. In casein medium, the matrix metalloprotease, Lap1, was also upregulated and secreted in addition to Mep and Alp1. These findings suggest that A. fumigatus is able to detect different complex proteins available as substrates in its environment and regulate protease secretion accordingly. There is a requirement for the standardisation of A. fumigatus allergen extracts used both in clinical diagnosis of A. fumigatus allergy and in research studies. Published by Elsevier, copyright by British Mycological Society 2012-09 /pmc/articles/PMC3605576/ /pubmed/22954343 http://dx.doi.org/10.1016/j.funbio.2012.07.004 Text en © 2012 British Mycological Society. Published by Elsevier Ltd. All rights reserved. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Farnell, Edward Rousseau, Karine Thornton, David J. Bowyer, Paul Herrick, Sarah E.
spellingShingle	Farnell, Edward Rousseau, Karine Thornton, David J. Bowyer, Paul Herrick, Sarah E. Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
author_facet	Farnell, Edward Rousseau, Karine Thornton, David J. Bowyer, Paul Herrick, Sarah E.
author_sort	Farnell, Edward
title	Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
title_short	Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
title_full	Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
title_fullStr	Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
title_full_unstemmed	Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates
title_sort	expression and secretion of aspergillus fumigatus proteases are regulated in response to different protein substrates
description	The ubiquitous filamentous fungus Aspergillus fumigatus secretes a number of allergens with protease activity and has been linked to a variety of allergic conditions such as Severe Asthma with Fungal Sensitization (SAFS) and Allergic Bronchopulmonary Aspergillosis (ABPA). However, it is unclear which allergen proteases are being secreted during fungal invasion and whether the local biological environment regulates their expression. Understanding the dynamic expression of allergen proteases during growth of A. fumigatus may lead to further characterisation of the pathogenesis of these disorders as well as improved standardisation in the commercial production of these allergens. Secretion of proteases during germination and early growth of A. fumigatus was investigated in response to various complex protein sources (pig lung homogenate, mucin or casein). Protease inhibitor studies demonstrated that A. fumigatus (AF293 strain) secretes predominately serine proteases during growth in pig lung based medium and mainly metalloproteases during growth in casein based medium but suppressed protease secretion in unmodified Vogel's minimal medium and secreted both types in mucin based medium. Analysis of gene transcription and protein identification by mass spectrometry showed that the matrix metalloprotease, Mep/Asp f 5 and the serine protease, Alp1/Asp f 13, were upregulated and secreted during growth in pig lung medium, whereas Alp1 was predominately expressed and secreted in mucin based medium. In casein medium, the matrix metalloprotease, Lap1, was also upregulated and secreted in addition to Mep and Alp1. These findings suggest that A. fumigatus is able to detect different complex proteins available as substrates in its environment and regulate protease secretion accordingly. There is a requirement for the standardisation of A. fumigatus allergen extracts used both in clinical diagnosis of A. fumigatus allergy and in research studies.
publisher	Published by Elsevier, copyright by British Mycological Society
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605576/
_version_	1611964679197818880

Expression and secretion of Aspergillus fumigatus proteases are regulated in response to different protein substrates

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