Biomaterial Database

Interaction between the pili of Pseudomonas aeruginosa PAK and its carbohydrate receptor beta-D-GalNAc(1-->4)beta-D-Gal analogs. 1998

F Schweizer, and H Jiao, and O Hindsgaul, and W Y Wong, and R T Irvin

Department of Chemistry, University of Alberta, Edmonton, Canada.

Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell surface receptors. Previously, it has been shown that the pilus adhesin of P. aeruginosa PAK binds to the ganglioside asialo-GM1. In particular, it was found that the carbohydrate sequence beta-D-GalNAc(1-->4)beta-D-Gal is the minimal carbohydrate receptor sequence of asialo-GM1. To study the binding specificity of P. aeruginosa, O-modified and N-modified sugar analogs, where each hydroxyl group was substituted either by O-methyl or O-propyl and the acetamido group was changed to a propionamido group, were synthesized. The sugar analogs were evaluated as inhibitors in a competitive solid phase binding assay. The results demonstrate that the pili of P. aeruginosa PAK accepts a variety of sugar analogs possessing the sequence beta-D-GalNAc(1-->4)beta-D-Gal. Most sugar analogs bind with a similar order of magnitude (50% inhibitory concentration (IC50) = 60-130 microM) except for the 2-O-propyl derivative 7 (IC50 = 8 +/- 4 microM) compared with an IC50 of 79 +/- 18 microM for the native compound. The significant increase in binding affinity of 2-O-propyl derivative 7 suggests that improved inhibitors of adhesion may be prepared by introducing a hydrophobic side chain at the 2-position of galactose.

UI	MeSH Term	Description	Entries
D010861	Fimbriae, Bacterial	Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly Enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins (ADHESINS, BACTERIAL). Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of "pili", which is confined to sex pili (PILI, SEX).	Bacterial Fimbriae,Bacterial Pili,Common Fimbriae,Common Pili,Pili, Bacterial,Pili, Common,Bacterial Fimbria,Bacterial Pilus,Common Fimbria,Common Pilus,Fimbria, Bacterial,Pilus, Bacterial,Fimbria, Common,Fimbriae, Common,Pilus, Common
D011550	Pseudomonas aeruginosa	A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.	Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D011971	Receptors, Immunologic	Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.	Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D002240	Carbohydrate Sequence	The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.	Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D004848	Epithelium	The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body.	Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D005677	G(M1) Ganglioside	A specific monosialoganglioside that accumulates abnormally within the nervous system due to a deficiency of GM1-b-galactosidase, resulting in GM1 gangliosidosis.	GM1 Ganglioside,Monosialosyl Tetraglycosyl Ceramide,GM1a Monosialoganglioside,Ceramide, Monosialosyl Tetraglycosyl,Ganglioside, GM1,Monosialoganglioside, GM1a,Tetraglycosyl Ceramide, Monosialosyl
D001422	Bacterial Adhesion	Physicochemical property of fimbriated (FIMBRIAE, BACTERIAL) and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity.	Adhesion, Bacterial,Adhesions, Bacterial,Bacterial Adhesions
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001667	Binding, Competitive	The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.	Competitive Binding
D050260	Carbohydrate Metabolism	Cellular processes in biosynthesis (anabolism) and degradation (catabolism) of CARBOHYDRATES.	Metabolism, Carbohydrate