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Abstract
Muco-obstructive lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, primary ciliary dyskinesia, and non-CF bronchiectasis, are characterized by hypersecretion of mucins, dehydration of the mucus, and development of obstructions. Mucociliary clearance from both ciliary action and cough is disrupted due to the high viscoelasticity of the affected mucus, leading to subsequent failure to clear pathogens from the airway. Respiratory infections are one of the leading causes of morbidity and mortality for people with muco-obstructive lung disease even with antibiotic therapies and therapeutics designed to improve mucus clearance.
Pseudomonas aeruginosa and Staphylococcus aureus are bacterial pathogens prevalent in muco-obstructive lung disease. Mechanisms of virulence for both have been investigated in the context of respiratory infections, but a missing facet of this interaction between the mucus and bacteria is the effect of the bacteria on viscoelasticity. Our work has determined that both bacteria are capable of directly increasing the viscoelasticity and decreasing the transportability of artificial mucus. P. aeruginosa utilizes a putative mucinase and production of exopolysaccharides to alter viscoelasticity. S. aureus effects on viscoelasticity are determined by mucin concentration and polymer size and by phenol-soluble modulins. Our results indicate that the bacteria directly alter mucus viscoelasticity in a manner that can impede mucociliary transport and that disruption of these mechanisms may reduce the likelihood of developing mucus obstructions and exacerbations for people with muco-obstructive lung diseases.