An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection
| Autor: | Branagh Crealock-Ashurst, Marwa M. Hassan, Matthew N Hurley, Esther Sweeney, Freya Harrison, Alicia G Harley Henriques, Alan R. Smyth, María Ángeles Tormo-Más, Niamh E. Harrington |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Multidrug tolerance business.industry 030106 microbiology respiratory system medicine.disease_cause medicine.disease Microbiology Mucus Cystic fibrosis Phenotype 03 medical and health sciences Chronic infection 030104 developmental biology Antibiotic resistance Staphylococcus aureus medicine business Ex vivo RC |
| ISSN: | 1350-0872 |
| Popis: | Staphylococcus aureusis the most prevalent organism isolated from the airways of people with cystic fibrosis (CF), predominantly 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 establishedex vivomodel of CF infection comprising porcine bronchiolar tissue and synthetic mucus,S. aureusdemonstrates 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 toS. aureusin people with CF. |
| Databáze: | OpenAIRE |
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