Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens
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 fr...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 19; pp. 7868 - 7873 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
07.05.2013
National Acad Sciences |
Subjects | |
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Abstract | 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. |
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AbstractList | 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. 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. 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. [PUBLICATION ABSTRACT] |
Author | Whitfield, Chris Stupak, Jacek Willis, Lisa M. Richards, Michele R. Li, Jianjun Lowary, Todd L. |
Author_xml | – sequence: 1 givenname: Lisa M. surname: Willis fullname: Willis, Lisa M. – sequence: 2 givenname: Jacek surname: Stupak fullname: Stupak, Jacek – sequence: 3 givenname: Michele R. surname: Richards fullname: Richards, Michele R. – sequence: 4 givenname: Todd L. surname: Lowary fullname: Lowary, Todd L. – sequence: 5 givenname: Jianjun surname: Li fullname: Li, Jianjun – sequence: 6 givenname: Chris surname: Whitfield fullname: Whitfield, Chris |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23610430$$D View this record in MEDLINE/PubMed |
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Notes | http://dx.doi.org/10.1073/pnas.1222317110 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: L.M.W. and C.W. designed research; L.M.W., J.S., M.R.R., and J.L. performed research; L.M.W., J.S., M.R.R., T.L.L., J.L., and C.W. analyzed data; and L.M.W., M.R.R., T.L.L., J.L., and C.W. wrote the paper. Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved April 1, 2013 (received for review December 20, 2012) |
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Snippet | Bacterial capsules are surface layers made of long-chain polysaccharides. They are anchored to the outer membrane of many Gram-negative bacteria, including... |
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SubjectTerms | 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 |
Title | Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens |
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