Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 19; pp. 7868 - 7873
• Main Authors: Willis, Lisa M., Stupak, Jacek, Richards, Michele R., Lowary, Todd L., Li, Jianjun, Whitfield, Chris
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07.05.2013; National Acad Sciences
• Subjects: Adenosine triphosphatase; Adenosine Triphosphate - metabolism; ATP binding cassette transporters; ATP-Binding Cassette Transporters - metabolism; Bacteria; Bacterial Capsules - metabolism; Binding sites; Biochemistry; Biological Sciences; Biological Transport; Biosynthesis; Capsules; Carbohydrates; Enzymes; Escherichia coli; Escherichia coli - metabolism; Glycolipids; Glycolipids - metabolism; Gram-negative bacteria; Gram-Negative Bacteria - metabolism; Lipids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Methylation; Mutation; Neisseria meningitidis - metabolism; Pathogens; Polysaccharides; Polysaccharides - metabolism; Virulence Factors - metabolism; capsule assembly; polysaccharide export
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1222317110

Bacterial capsules are surface layers made of long-chain polysaccharides. They are anchored to the outer membrane of many Gram-negative bacteria, including pathogens such as Escherichia coli , Neisseria meningitidis , Haemophilus influenzae , and Pasteurella multocida . Capsules protect pathogens from host defenses including complement-mediated killing and phagocytosis and therefore represent a major virulence factor. Capsular polysaccharides are synthesized by enzymes located in the inner (cytoplasmic) membrane and are then translocated to the cell surface. Whereas the enzymes that synthesize the polysaccharides have been studied in detail, the structure and biosynthesis of the anchoring elements have not been definitively resolved. Here we determine the structure of the glycolipid attached to the reducing terminus of the polysialic acid capsular polysaccharides from E. coli K1 and N. meningitidis group B and the heparosan-like capsular polysaccharide from E. coli K5. All possess the same unique glycolipid terminus consisting of a lyso-phosphatidylglycerol moiety with a β-linked poly-(3-deoxy- d - manno -oct-2-ulosonic acid) (poly-Kdo) linker attached to the reducing terminus of the capsular polysaccharide.