Margalit, Anatte and Kavanagh, Kevin and Carolan, James C. (2020) Characterization of the proteomic response of A549 cells following sequential exposure to Aspergillus fumigatus and Pseudomonas aeruginosa. Journal of Proteome Research, 19. pp. 279-291. ISSN 1535-3893

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Abstract

Aspergillus fumigatus and Pseudomonas aeruginosa are the most prevalent fungal and bacterial pathogens associated with cystic-fibrosisrelated 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.

Item Type:	Article
Additional Information:	Cite as: J. Proteome Res. 2020, 19, 279−291
Keywords:	Aspergillus; cellular response; cystic fibrosis; fungal infection; Pseudomonas;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	13512
Identification Number:	https://doi.org/10.1021/acs.jproteome.9b00520
Depositing User:	James Carolan
Date Deposited:	10 Nov 2020 14:48
Journal or Publication Title:	Journal of Proteome Research
Publisher:	American Chemical Society
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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