Oligosaccharide receptor mimics inhibit Legionella pneumophila attachment to human respiratory epithelial cells.
Legionnaire's disease is caused by the intracellular pathogen Legionella pneumophila, presenting as an acute pneumonia. Attachment is the key step during infection, often relying on an interaction between host cell oligosaccharides and bacterial adhesins. Inhibition of this interaction by receptor mimics offers possible novel therapeutic treatments. L. pneumophila attachment to the A549 cell line was significantly reduced by treatment with tunicamycin (73.6%) and sodium metaperiodate (63.7%). This indicates the importance of cell surface oligosaccharide chains in adhesion. A number of putative anti-adhesion compounds inhibited attachment to the A549 and U937 cell lines. The most inhibitory compounds were polymeric saccharides, GalNAcbeta1-4Gal, Galbeta1-4GlcNAc and para-nitrophenol. These compounds inhibited adhesion to a range of human respiratory cell lines, including nasal epithelial, bronchial epithelial and alveolar epithelial cell lines and the human monocytic cell line, U937. Some eukaryotic receptors for L. pneumophila were determined to be the glycolipids, asialo-GM1 and asialo-GM2 that contain the inhibitory saccharide moiety, GalNAcbeta1-4Gal. The identified compounds have the potential to be used as novel treatments for Legionnaire's disease.
Thomas
Richard J
RJ
Defence, science and technology laboratories, Biomedical Sciences, CBS Porton Down, Salisbury, Wiltshire, UK.rjthomas@dstl.gov.uk
Brooks
Tim J
TJ
D018829:Adhesins, Bacterial / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D002460:Cell Line; D015169:Colony Count, Microbial; D004847:Epithelial Cells / Q000382:microbiology*; D005677:G(M1) Ganglioside / Q000032:analysis; D005732:Gangliosides; D006017:Glycolipids / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis; D006801:Humans; D007700:Kinetics; D016952:Legionella pneumophila / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D010504:Periodic Acid / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D013997:Time Factors; D014415:Tunicamycin / Q000494:pharmacology; D020298:U937 Cells
D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D005732:Gangliosides; D006017:Glycolipids; D006028:Glycosphingolipids; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D010504:Periodic Acid; D014415:Tunicamycin; C038244:ganglio-N-triaosylceramide; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; C009288:metaperiodate