The effect of Staphylococcus aureus on the persistence of Pseudomonas aeruginosa due to aggregation in cystic fibrosis airway infections

Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) co-infection has been associated with worse clinical outcomes in people with cystic fibrosis (pwCF); however, the nature of their interaction is poorly understood. This was a 3-year prospective study of pwCF with chronic Pa infection. Pa, Sa,and staphylococcal protein A (SpA) were visualized by confocal microscopy in sputum samples obtained at baseline, exacerbation, after antibiotic treatment,and recovery. Forty-five participants were enrolled. At exacerbation, Pa biovolume and aggregate number increased in children, as well as geospatial distancing of Pa from Sa. With IV antibiotics, Pa (0.5–20 μm diameter) decreased significantly more than large Pa aggregates (>20 μm). Increasing sputum SpA concentrations were correlated with higher Pa biovolume in children ( p = 0.04, r=0.54). Within CF airways, Pa and Sa occupy spatially distinct niches but may interact through SpA production in children. Large Pa aggregates persisted despite antibiotics, indicating sustained infection.