Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection

ABSTRACT Aspergillus fumigatus is one of the most common airborne molds capable of causing mycoses and allergies in humans. During infection, fungal surface proteins mediate the first contact with the human immune system to evade immune responses or to induce hypersensitivity. Several methods have b...

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Autores principales:	Lei-Jie Jia, Thomas Krüger, Matthew G. Blango, Ferdinand von Eggeling, Olaf Kniemeyer, Axel A. Brakhage
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus fumigatus surface biotinylation surfome LC-MS/MS allergens heat shock protein Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/04dbe7362d1b46078c8ae59b114d7349
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spelling	oai:doaj.org-article:04dbe7362d1b46078c8ae59b114d73492021-11-15T15:30:51ZBiotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection10.1128/mSphere.00535-202379-5042https://doaj.org/article/04dbe7362d1b46078c8ae59b114d73492020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00535-20https://doaj.org/toc/2379-5042ABSTRACT Aspergillus fumigatus is one of the most common airborne molds capable of causing mycoses and allergies in humans. During infection, fungal surface proteins mediate the first contact with the human immune system to evade immune responses or to induce hypersensitivity. Several methods have been established for surface proteomics (surfomics). Biotinylation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of peptides is a particularly efficient method to identify the surface-exposed regions of proteins that potentially mediate interaction with the host. After biotinylation of surface proteins during spore germination, we detected 231 different biotinylated surface proteins (including several well-known proteins such as RodA, CcpA, and DppV; allergens; and heat shock proteins [HSPs]), as well as some previously undescribed surface proteins. The dynamic change of the surface proteome was illustrated by detection of a relatively high number of proteins exclusively at one developmental stage. Using immunofluorescence microscopy, we confirmed the surface localization of several HSPs of the HSP70 family, which may have moonlighting functions. Collectively, by comparing our data with data representative of previously published A. fumigatus surface proteomes, our study generated a comprehensive data set corresponding to the A. fumigatus surfome and uncovered the surface-exposed regions of many proteins on the surface of conidia or hyphae. These surface-exposed regions are candidates for direct interaction with host cells and may represent antigenic epitopes that either induce protective immune responses or mediate immune evasion. Thus, our data sets provided and compiled here represent reasonable immunotherapy and diagnostic targets for future investigations. IMPORTANCE Aspergillus fumigatus is the most important airborne human-pathogenic mold, capable of causing both life-threatening invasive pulmonary aspergillosis in immunocompromised patients and allergy-inducing infections in individuals with atopic allergy. Despite its obvious medical relevance, timely diagnosis and efficient antifungal treatment of A. fumigatus infection remain major challenges. Proteins on the surface of conidia (asexually produced spores) and mycelium directly mediate host-pathogen interaction and also may serve as targets for diagnosis and immunotherapy. However, the similarity of protein sequences between A. fumigatus and other organisms, sometimes even including the human host, makes selection of targets for immunological-based studies difficult. Here, using surface protein biotinylation coupled with LC-MS/MS analysis, we identified hundreds of A. fumigatus surface proteins with exposed regions, further defining putative targets for possible diagnostic and immunotherapeutic design.Lei-Jie JiaThomas KrügerMatthew G. BlangoFerdinand von EggelingOlaf KniemeyerAxel A. BrakhageAmerican Society for MicrobiologyarticleAspergillus fumigatussurface biotinylationsurfomeLC-MS/MSallergensheat shock proteinMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus surface biotinylation surfome LC-MS/MS allergens heat shock protein Microbiology QR1-502
spellingShingle	Aspergillus fumigatus surface biotinylation surfome LC-MS/MS allergens heat shock protein Microbiology QR1-502 Lei-Jie Jia Thomas Krüger Matthew G. Blango Ferdinand von Eggeling Olaf Kniemeyer Axel A. Brakhage Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
description	ABSTRACT Aspergillus fumigatus is one of the most common airborne molds capable of causing mycoses and allergies in humans. During infection, fungal surface proteins mediate the first contact with the human immune system to evade immune responses or to induce hypersensitivity. Several methods have been established for surface proteomics (surfomics). Biotinylation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of peptides is a particularly efficient method to identify the surface-exposed regions of proteins that potentially mediate interaction with the host. After biotinylation of surface proteins during spore germination, we detected 231 different biotinylated surface proteins (including several well-known proteins such as RodA, CcpA, and DppV; allergens; and heat shock proteins [HSPs]), as well as some previously undescribed surface proteins. The dynamic change of the surface proteome was illustrated by detection of a relatively high number of proteins exclusively at one developmental stage. Using immunofluorescence microscopy, we confirmed the surface localization of several HSPs of the HSP70 family, which may have moonlighting functions. Collectively, by comparing our data with data representative of previously published A. fumigatus surface proteomes, our study generated a comprehensive data set corresponding to the A. fumigatus surfome and uncovered the surface-exposed regions of many proteins on the surface of conidia or hyphae. These surface-exposed regions are candidates for direct interaction with host cells and may represent antigenic epitopes that either induce protective immune responses or mediate immune evasion. Thus, our data sets provided and compiled here represent reasonable immunotherapy and diagnostic targets for future investigations. IMPORTANCE Aspergillus fumigatus is the most important airborne human-pathogenic mold, capable of causing both life-threatening invasive pulmonary aspergillosis in immunocompromised patients and allergy-inducing infections in individuals with atopic allergy. Despite its obvious medical relevance, timely diagnosis and efficient antifungal treatment of A. fumigatus infection remain major challenges. Proteins on the surface of conidia (asexually produced spores) and mycelium directly mediate host-pathogen interaction and also may serve as targets for diagnosis and immunotherapy. However, the similarity of protein sequences between A. fumigatus and other organisms, sometimes even including the human host, makes selection of targets for immunological-based studies difficult. Here, using surface protein biotinylation coupled with LC-MS/MS analysis, we identified hundreds of A. fumigatus surface proteins with exposed regions, further defining putative targets for possible diagnostic and immunotherapeutic design.
format	article
author	Lei-Jie Jia Thomas Krüger Matthew G. Blango Ferdinand von Eggeling Olaf Kniemeyer Axel A. Brakhage
author_facet	Lei-Jie Jia Thomas Krüger Matthew G. Blango Ferdinand von Eggeling Olaf Kniemeyer Axel A. Brakhage
author_sort	Lei-Jie Jia
title	Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
title_short	Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
title_full	Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
title_fullStr	Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
title_full_unstemmed	Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection
title_sort	biotinylated surfome profiling identifies potential biomarkers for diagnosis and therapy of <named-content content-type="genus-species">aspergillus fumigatus</named-content> infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/04dbe7362d1b46078c8ae59b114d7349
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Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Infection

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