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Disparate proteome responses of pathogenic and nonpathogenic aspergilli to human serum measured by activity-based protein profiling (ABPP).

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Disparate proteome responses of pathogenic and nonpathogenic aspergilli to human serum measured by activity-based protein profiling (ABPP).

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wiedner, Susan D. Ansong, Charles Webb-Robertson, Bobbie-Jo Pederson, LeeAnna M. Fortuin, Suereta Hofstad, Beth A. Shukla, Anil K. Panisko, Ellen A. Smith, Richard D. Wright, Aaron T.
Description	Country affiliation: United States Author Affiliation: Wiedner SD ( Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.)
Abstract	Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. There is high genomic synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. We applied activity-based protein profiling to compare unique or overexpressed activity-based probe-reactive proteins of all three fungi over time in minimal media growth and in response to human serum. We found 360 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culture in serum. Though the fungi are highly orthologous, A. fumigatus has a significantly greater number of ABP-reactive proteins across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Activity-based protein profiling identified a number of processes that were induced by human serum in A. fumigatus relative to N. fischeri and A. clavatus. These included actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher activity-based probe-protein reaction over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely pathogenic aspergilli. These unique activity-based probe-protein responses to culture condition may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M112.026534
Journal	Molecular & Cellular Proteomics
Issue Number	7
Volume Number	12
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Aspergillus Fumigatus Metabolism Fungal Proteins Growth & Development Pathogenicity Protein Array Analysis Proteome Serum Virulence Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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Disparate Proteome Responses of Pathogenic and Nonpathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)*

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