Proteomic analysis uncovers distinct signatures of bacterial-viral coinfections in cystic fibrosis cells

Adrian Endres*, Philipp Kastl, Helena Boland, Christian Hügel, Konstantinos Kalogeropoulos, Peter Braubach, Danny Jonigk, Michael Hogardt, Gernot Rohde, Ulrich Auf Dem Keller, Carla Bellinghausen

*Corresponding author for this work

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

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.
Original languageEnglish
Article numberOA1495
JournalThe European Respiratory Journal
Volume58
Issue numberSuppl. 65
ISSN0903-1936
DOIs
Publication statusPublished - 2021
EventERS International Congress 2021 - Virtual event
Duration: 5 Sep 20218 Sep 2021

Conference

ConferenceERS International Congress 2021
CityVirtual event
Period05/09/202108/09/2021

Fingerprint

Dive into the research topics of 'Proteomic analysis uncovers distinct signatures of bacterial-viral coinfections in cystic fibrosis cells'. Together they form a unique fingerprint.

Cite this