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

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