Abstract
Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung.
Highlights
Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein cause an imbalance of ion transport that leads to mucus hyperviscosity and impaired mucociliary clearance [1]
Persistent CF lung infections are composed of hundreds of microbial taxa whose interactions contribute to respiratory failure
We reveal that a subset of CF microbiota is capable of fermenting mucins for carbon and energy which, in-turn, can support the carbon demands of other
Summary
Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein cause an imbalance of ion transport that leads to mucus hyperviscosity and impaired mucociliary clearance [1]. Within the airways, prolonged residence time of mucus provides a stagnant nidus for chronic bacterial infections–the predominant cause of mortality in CF patients [2]. The respiratory tract contains a number of host compounds that can be used by microbes as nutrient sources, including immunoglobulins, cytokines, defensins and lactoferrin [8,9], yet these are unlikely to be present at concentrations to support the dense microbiota of the CF airways [10,11,12,13]. Studies of CF sputum from adult patients have shown an abundance of small molecules that can support the growth of pathogens in vitro, including sugars, fatty acids, phospholipids, and amino acids [14,15,16,17]. The mechanism by which these compounds reach high abundance in airway mucus remains poorly defined
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