16S Illumina MiSeq bacterial metagenomics reveal CF lung microbiome

We conclude that: 1) Both MUC5AC and MUC5B are hyperconcentrated in CF secretions and contribute to CF airway disease pathogenesis, 2) Both MUC5AC and MUC5B in CF are subject to enzymatic cleavage by a combination of glycosylhydrolases from pathogens and proteases from neutrophils. 3) These enzymatic modifications slightly but not significantly alter the molecular weight of mucins, while likely providing sugar substrates for bacteria and rendering CF mucins more susceptible to large molecular weight reductions by mucolytics targeting S-S bonds. And finally 4) The shift in CF mucin O-linked glycan diversity toward greater sialylation and less sulfation, with the notable exception of specific sulfated glycans of significant inflammatory importance, e.g. sulfo-sialyl-Lewis type structures, which were enriched in CF mucins, suggests an interaction among the airway epithelium, mucosal gland cells, and pathogens which promulgates proteomic and glycomic changes that are essential components of CF pathogenesis.