title: Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.
abstract: Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Wiedner
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Burnum
authors.forename: LeeAnna M
authors.initials: LM
authors.lastname: Pederson
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Anderson
authors.forename: Suereta
authors.initials: S
authors.lastname: Fortuin
authors.forename: Lacie M
authors.initials: LM
authors.lastname: Chauvigné-Hines
authors.forename: Anil K
authors.initials: AK
authors.lastname: Shukla
authors.forename: Charles
authors.initials: C
authors.lastname: Ansong
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Panisko
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wright
mesh_terms: D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001671:Biochemistry / Q000379:methods; D016895:Culture Media, Serum-Free / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008168:Lung / Q000382:microbiology; D008171:Lung Diseases / Q000382:microbiology; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D008956:Models, Chemical; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods; D044967:Serum / Q000382:microbiology*; D013997:Time Factors
chemical_list: D016895:Culture Media, Serum-Free; D005656:Fungal Proteins