Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells.
The basis for the unique association of Pseudomonas aeruginosa and the cystic fibrosis (CF) lung has remained obscure despite major advances in the understanding of the molecular genetic cause of this disease. There is evidence to suggest that abnormalities in CF transmembrane conductance regulator function result in alterations in the glycosylation of epithelial components. The number of asialoGM1 residues, as representative of a class of glycolipids which contain a GalNAc beta 1-4Gal sequence for P. aeruginosa attachment, was quantified by flow cytometric studies of respiratory epithelial cells in primary culture from both CF patients and normal subjects. Superficial asialoGM1 was detected on 12% of the CF cells as compared with 2.9% of the cells from normal control subjects (P = 0.03, chi 2 = 4.73), and more asialoGM1 residues were exposed on CF cells after modification by P. aeruginosa exoproducts. AsialoGM1, but not the sialylated glycolipid GM1, was demonstrated to be a receptor for 125I-labeled P. aeruginosa pilin, a major adhesin for this organism, and exogenous asialoGM1 was found to competitively inhibit P. aeruginosa adherence to epithelial cells, thus, confirming the biological role of the asialoGM1 receptor. Quantitative and qualitative differences in the sialylation of superficial glycolipids in CF epithelial cells may directly contribute to the colonization of the CF lung by P. aeruginosa.
Saiman
L
L
College of Physicians and Surgeons, Columbia University, New York 10032.
Prince
A
A
D001422:Bacterial Adhesion / Q000502:physiology*; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004848:Epithelium / Q000737:chemistry / Q000502:physiology; D010861:Fimbriae, Bacterial / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000032:analysis / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009298:Nasal Polyps / Q000473:pathology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D012016:Reference Values
D006017:Glycolipids; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D002772:Cholera Toxin