title: Characterization of lipopolysaccharides of polymyxin-resistant and polymyxin-sensitive Klebsiella pneumoniae O3.
abstract: Lipopolysaccharides isolated from the polymyxin-resistant Klebsiella pneumoniae O3 mutant OM-5 and its polymyxin-sensitive parent LEN-1 were analyzed for chemical composition, and their lipid A portions were structurally characterized. The lipopolysaccharide of OM-5 contained approximately five times more 4-amino-4-deoxy-L-arabinopyranose than that of LEN-1. Other saccharide and phosphate components exhibited no significant differences. Structural characterization, including analyses by phosphorus magnetic resonance spectroscopy and by fast atom bombardment mass spectrometry, revealed a novel type of lipid A. In the OM-5 lipopolysaccharide, both phosphates of lipid A were almost totally present as phosphodiesters with 4-amino-4-deoxy-L-arabinopyranose. In the sensitive-type LEN-1 lipid A, the extent of this substitution was much lower, especially in the glycosidically linked phosphate. Phosphate in these K. pneumoniae lipopolysaccharides was almost exclusively found in lipid A. These results show that cationic substituents of phosphates of lipid A play a decisive role in determining polymyxin reactivity. OM-5 was also found to contain a large proportion of heptaacyl lipid A, which represented only a small fraction of lipid A in LEN-1.
authors.affiliation: Department of Vaccines, KTL, Helsinki, Finland.
authors.forename: I M
authors.initials: IM
authors.lastname: Helander
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: I
authors.initials: I
authors.lastname: Kilpeläinen
authors.forename: R
authors.initials: R
authors.lastname: Kostiainen
authors.forename: B
authors.initials: B
authors.lastname: Lindner
authors.forename: K
authors.initials: K
authors.lastname: Nummila
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D004352:Drug Resistance, Microbial; D007711:Klebsiella pneumoniae / Q000737:chemistry* / Q000187:drug effects; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D008969:Molecular Sequence Data; D011113:Polymyxins / Q000494:pharmacology*; D013057:Spectrum Analysis
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides; D011113:Polymyxins