title: Host mucin glycosylation plays a role in bacterial adhesion in lungs of individuals with cystic fibrosis.
abstract: Malfunction of the cell surface glycoprotein, cystic fibrosis transmembrane conductance regulator, is the molecular hallmark of cystic fibrosis (CF), causing salt imbalance across the lung epithelium and biochemical and biophysical alterations of the mucous secretion and airway surfaces. Abnormal glycosylation of both secreted and membrane-tethered airway mucins in CF hosts are reported by a substantial body of literature and correlates with bacterial infection and inflammation in CF airways, features that are linked to the CF pathology. It is established that Pseudomonas aeruginosa and other CF-typic bacteria use the altered host mucin glycosylation as receptors for adhesion by dedicated lectins and adhesins recognizing an array of the aberrantly expressed glycan determinants. This review aims to describe the aberrant mucin glycosylation phenotype observed in CF airways relative to the non-CF equivalent by summarizing the wealth of literature on this topic. The possible causes and effects of altered glycosylation in the respiratory system are discussed. Specific attention is given to the adhesion mechanisms of the opportunistic P. aeruginosa, which utilizes the molecular alterations of the lung to gain access to the normally sterile airways. Finally, the emerging glycosylation-based therapeutics that show promising potential for reducing bacterial infection in individuals with CF by molecular mimicry mechanisms are discussed.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Vignesh
authors.initials: V
authors.lastname: Venkatakrishnan
authors.forename: Nicolle H
authors.initials: NH
authors.lastname: Packer
authors.forename: Morten
authors.initials: M
authors.lastname: Thaysen-Andersen
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D015195:Drug Design; D006031:Glycosylation; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D018716:Molecular Mimicry; D009077:Mucins / Q000378:metabolism*; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology
chemical_list: D009077:Mucins