Increased low-molecular-weight mucins in muco-obstructive airway disease limit Staphylococcus aureus growth

Muco-obstructive airway diseases result in an increase in mucus accumulation and a decrease in mucus clearance. MUC5B is the most abundant secreted mucin in the human airways, and MUC5B mucin strands dimerize to create the mucus mesh network in the healthy respiratory tract. In muco-obstructive airway diseases like cystic fibrosis (CF), immune cells and bacteria release enzymes that degrade MUC5B into smaller fragments that become entangled and compacted, contributing to pathogenesis. We utilized synthetic cystic fibrosis sputum media (SCFM) to examine how mucin polymers can impact Staphylococcus aureus, a common CF pathogen that persists despite highly effective modulator therapies to correct CF disease. We found that low-molecular-weight (LMW) mucin negatively impacts S. aureus survival and biofilm biomass compared to high-molecular-weight (HMW) mucin. Adding extracellular DNA to SCFM with LMW mucin was not sufficient to restore growth. LMW mucin had a broad negative impact on S. aureus laboratory strains and CF clinical isolates. We next tested other CF pathogens, including Pseudomonas aeruginosa and nontypeable Haemophilus influenzae, and saw no significant differences in growth in HMW or LMW mucin. LMW mucin did not significantly impact Staphylococcus epidermidis growth, indicating that there may be specific interactions with S. aureus. Overall, this work highlights how interactions with pathogenic mucins may limit S. aureus growth in the diseased airways while supporting low-level persistence, and its ability to thrive in the presence of longer mucin strands may help explain why S. aureus is well adapted to survive in the healthy respiratory tract.