Conference paper
Proteomic analysis uncovers distinct signatures of bacterial-viral coinfections in cystic fibrosis cells
Frankfurt University Hospital1
Department of Biotechnology and Biomedicine, Technical University of Denmark2
Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark3
Protease Network Degradomics, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark4
Hannover Medical School5
Pseudomonas aeruginosa (PA) is the dominating bacterial pathogen in cystic fibrosis (CF) lungs, whereas respiratory viruses can trigger exacerbations of CF lung disease. We studied in vitro how PA and Human Rhinovirus (HRV) infection influence each other. Differentiated bronchial epithelial cells from CF patients and healthy controls (HC) were repeatedly infected with a clinical PA isolate for 20 days and then coinfected with HRV.
Whole proteome analysis was combined with N-terminal enrichment by tandem mass tag (TMT)-terminal amine isotopic labeling of substrates (TAILS). In total, almost 6500 host, viral and bacterial proteins were detected. HRV infection led to increase in abundance of 50 proteins in CF and 44 proteins in HC cells, mainly interferon-induced and antigen-presenting proteins.
Compared to virus infection alone, coinfection with PA and HRV led to increased abundance of 25 host proteins in HC and lower levels of 5 proteins. In CF cells, additional proteins were detected with differential abundance. Host proteins with increased abundance included proteins linked to IL-1ß production (CARD8, ZFP91) and pathogen internalization (CAV1, NDRG1), while proteins with decreased levels included proteins with functions in immunity (HLA-B, TLR2), epithelial repair (DDR1) and ciliary movement (CFAP70).
Of note, coinfection with HRV also significantly affected the bacterial proteome. Our analysis highlights differences in host and bacterial proteomes during coinfections, distinct from changes induced by single pathogens. Understanding the interactions between PA, viruses and the host could improve management of virus-induced exacerbations in PA-infected patients with CF.
Language: | English |
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Year: | 2021 |
Proceedings: | ERS International Congress 2021 |
ISSN: | 09041850 and 09031936 |
Types: | Conference paper |
DOI: | 10.1183/13993003.congress-2021.OA1495 |
ORCIDs: | Kalogeropoulos, Konstantinos and Keller, Ulrich Auf Dem |