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An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic staphylococcus aureus infection

Sweeney, Esther; Harrington, Niamh E.; Harley Henriques, Alicia G.; Hassan, Marwa M.; Crealock-Ashurst, Branagh; Smyth, Alan R.; Hurley, Matthew N.; Tormo-Mas, Mar�a �ngeles; Harrison, Freya

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Authors

Esther Sweeney

Niamh E. Harrington

Alicia G. Harley Henriques

Marwa M. Hassan

Branagh Crealock-Ashurst

Alan R. Smyth

Matthew N. Hurley

Mar�a �ngeles Tormo-Mas

Freya Harrison



Abstract

Staphylococcus aureus is the most prevalent organism isolated from the airways of people with cystic fibrosis (CF), predomi-nantly early in life. Yet its role in the pathology of lung disease is poorly understood. In mice, and many experiments using cell lines, the bacterium invades cells or interstitium, and forms abscesses. This is at odds with the limited available clinical data: interstitial bacteria are rare in CF biopsies and abscesses are highly unusual. Bacteria instead appear to localize in mucus plugs in the lumens of bronchioles. We show that, in an established ex vivo model of CF infection comprising porcine bronchiolar tissue and synthetic mucus, S. aureus demonstrates clinically significant characteristics including colonization of the airway lumen, with preferential localization as multicellular aggregates in mucus, initiation of a small colony variant phenotype and increased antibiotic tolerance of tissue-associated aggregates. Tissue invasion and abscesses were not observed. Our results may inform ongoing debates relating to clinical responses to S. aureus in people with CF.

Citation

Sweeney, E., Harrington, N. E., Harley Henriques, A. G., Hassan, M. M., Crealock-Ashurst, B., Smyth, A. R., …Harrison, F. (2021). An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic staphylococcus aureus infection. Microbiology, 167(1), Article 000987. https://doi.org/10.1099/mic.0.000987

Journal Article Type Article
Acceptance Date Oct 12, 2020
Online Publication Date Nov 13, 2020
Publication Date 2021-01
Deposit Date Dec 29, 2020
Publicly Available Date Mar 28, 2024
Journal Microbiology
Print ISSN 1350-0872
Electronic ISSN 1465-2080
Publisher Microbiology Society
Peer Reviewed Peer Reviewed
Volume 167
Issue 1
Article Number 000987
DOI https://doi.org/10.1099/mic.0.000987
Keywords Microbiology
Public URL https://nottingham-repository.worktribe.com/output/5040311
Publisher URL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000987
Additional Information © Niamh E. Harrington, Alicia G. Harley Henriques, Marwa M. Hassan, Branagh Crealock- Ashurst, Alan R. Smyth, Matthew N. Hurley, María Ángeles Tormo- Mas and Freya Harrison, 2020. The definitive peer reviewed, edited version of this article is published in [Micrbiology, 167, 1, 2021, https://doi.org/10.1099/mic.0.000987

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