title: Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition.
abstract: The high incidence of colonization of the cystic fibrosis (CF) airway with Pseudomonas aeruginosa has been attributed to several mechanisms including increased numbers of asialoglycolipid receptors, which may be further increased by exposure to the bacterial exoproduct, neuraminidase. This study examined whether the adherence of P. aeruginosa to fresh CF respiratory epithelial cells can be reduced in vitro by anti-asialoGM1 (anti-aGM1) antibody, neuraminidase inhibition, or the use of asialoGM1 tetrasaccharide as a competitive inhibitor. CF nasal epithelial cells were incubated with a nonmucoid strain of P. aeruginosa, in the presence or absence of a polyclonal anti-aGM1 antibody, the neuraminidase inhibitor 2,3-dehydro-2-deoxy-N-acetyl-neuraminic acid (DANA), or the tetrasaccharide moiety of aGM1. Adherence of bacteria to the apical surface of ciliated epithelial cells was quantified using scanning electron microscopy. Incubation of the cells with bacteria in the presence of either anti-aGM1 antibody or DANA significantly reduced bacterial adherence by 51(7)%, (p<0.01), and 34(9)%, (p<0.01), respectively. In contrast, no significant effect on P. aeruginosa binding was seen in the presence of aGM1 tetrasaccharide. The data are consistent with previous studies on cultured cells, and suggest that the in vivo effects of such interventions should be explored as potential mechanisms to reduce Pseudomonas aeruginosa colonization in cystic fibrosis.
authors.affiliation: Dept of Paediatric Respiratory Medicine, Imperial College at the National Heart and Lung Institute, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: A
authors.initials: A
authors.lastname: Dewar
authors.forename: A
authors.initials: A
authors.lastname: Bush
authors.forename: T
authors.initials: T
authors.lastname: Pitt
authors.forename: D
authors.initials: D
authors.lastname: Gruenert
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000328:Adult; D001422:Bacterial Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology; D018709:Statistics, Nonparametric
chemical_list: D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D009439:Neuraminidase