Characterization of the Proteomic Response of A549 Cells Following Sequential Exposure to Aspergillus fumigatus and Pseudomonas aeruginosa

Aspergillus fumigatus and Pseudomonas aeruginosa are the most prevalent fungal and bacterial pathogens associated with cystic-fibrosis-related infections, respectively. P. aeruginosa eventually predominates as the primary pathogen, though it is unknown why this is the case. Label-free quantitative p...

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Bibliographic Details
Published in:Journal of proteome research 2020-01, Vol.19 (1), p.279-291
Main Authors: Margalit, Anatte, Kavanagh, Kevin, Carolan, James C
Format: Article
Language:English
Subjects:
A549 Cells
Aspergillosis - metabolism
Aspergillus fumigatus - pathogenicity
Cluster Analysis
Coinfection
Cystic Fibrosis - microbiology
Humans
Mitochondrial Proteins - metabolism
Proteome - analysis
Proteome - genetics
Proteome - metabolism
Proteomics - methods
Pseudomonas aeruginosa - pathogenicity
Pseudomonas Infections - metabolism
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Summary:Aspergillus fumigatus and Pseudomonas aeruginosa are the most prevalent fungal and bacterial pathogens associated with cystic-fibrosis-related infections, respectively. P. aeruginosa eventually predominates as the primary pathogen, though it is unknown why this is the case. Label-free quantitative proteomics was employed to investigate the cellular response of the alveolar epithelial cell line, A549, to coexposure of A. fumigatus and P. aeruginosa. These studies revealed a significant increase in the rate of P. aeruginosa proliferation where A. fumigatus was present. Shotgun proteomics performed on A549 cells exposed to either A. fumigatus or P. aeruginosa or to A. fumigatus and P. aeruginosa sequentially revealed distinct changes to the host cell proteome in response to either or both pathogens. While key signatures of infection were retained among all pathogen-exposed groups, including changes in mitochondrial activity and energy output, the relative abundance of proteins associated with endocytosis, phagosomes, and lysosomes was decreased in sequentially exposed cells compared to cells exposed to either pathogen. Our findings indicate that A. fumigatus renders A549 cells unable to internalize bacteria, thus providing an environment in which P. aeruginosa can proliferate. This research provides novel insights into the whole-cell proteomic response of A549 cells to A. fumigatus and P. aeruginosa and highlights distinct differences in the proteome following sequential exposure to both pathogens, which may explain why P. aeruginosa can predominate.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.9b00520