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Structure type: polymer chemical repeating unit
Trivial name: O-glycan
Compound class: CPS
Contained glycoepitopes: IEDB_130648,IEDB_135813,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_21,SB_7

• Article ID: 4562
  Lees-Miller RG, Iwashkiw JA, Scott NE, Seper A, Vinogradov E, Schild S, Feldman MF "A common pathway for O-linked protein-glycosylation and synthesis of capsule in Acinetobacter baumannii" - Molecular Microbiology 89(5) (2013) 816-830
  

  Multi-drug resistant strains of Acinetobacter baumannii are increasingly being isolated in hospitals worldwide. Among the virulence factors identified in this bacterium there is a general O-glycosylation system that appears to be important for biofilm formation and virulence, and the capsular polysaccharide, which is essential for resistance to complement killing. In this work, we identified a locus that is responsible for the synthesis of the O-pentasaccharide found on the glycoproteins. Besides the enzymes required for the assembly of the glycan, additional proteins typically involved in polymerization and transport of capsule were identified within or adjacently to the locus. Mutagenesis of PglC, the initiating glycosyltransferase prevented the synthesis of both glycoproteins and capsule, resulting in abnormal biofilm structures and attenuated virulence in mice. These results, together with the structural analysis of A. baumannii 17978 capsular polysaccharide via NMR, demonstrated that the pentasaccharides that decorate the glycoproteins are also the building blocks for capsule biosynthesis. Two linked subunits, but not longer glycan chains, were detected on proteins via MS. The discovery of a bifurcated pathway for O-glycosylation and capsule synthesis not only provides insight into the biology of A. baumannii but also identifies potential novel candidates for intervention against this emerging pathogen.

  Acinetobacter baumannii, capsular polysaccharide, capsule biosynthesis, genetic locus, O-pentasaccharide

  NCBI PubMed ID: 23782391
  Publication DOI: 10.1111/mmi.12300
  Journal NLM ID: 8712028
  Publisher: Blackwell Publishing
  Correspondence: mfeldman@ualberta.ca
  Institutions: Alberta Glycomics Centre, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
  Methods: 13C NMR, 1H NMR, NMR-2D, SDS-PAGE, DNA techniques, Western blotting, biological assays, microscopy, CID-MS, HILIC-MS
  
   
  
  Acinetobacter baumannii ATCC 17978
  CSDB ID 29254 (all data & tools)
• Article ID: 4819
  Giguere D "Surface polysaccharides from Acinetobacter baumannii: Structures and syntheses" - Carbohydrate Research 418 (2015) 29-43
  

  The emergence of multidrug-resistance Acinetobacter baumannii requires novel approaches for prevention, treatment and diagnosis. The structures of surface polysaccharides from A. baumannii are valuable tools to understand pathogenesis, virulence and immunogenicity. The synthesis of bacterial mono- or polysaccharides may result in novel probes to become important therapeutic options in the fight against A. baumannii. This report exemplifies the relevance of glycochemistry for the development of new antibiotics.

  lipopolysaccharides, capsular polysaccharides, Acinetobacter, Acinetobacter baumannii, polysaccharide synthesis, surface polysaccharides

  NCBI PubMed ID: 26531136
  Publication DOI: 10.1016/j.carres.2015.10.001
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: denis.giguere@chm.ulaval.ca
  Institutions: Département de Chimie, Université Laval, Québec City, Québec, Canada G1V 0A6
  
   
  
  Acinetobacter baumannii ATCC 17978
  CSDB ID 30940 (all data & tools)
• Article ID: 5056
  Yang FL, Lou TC, Kuo SC, Wu WL, Chern J, Lee YT, Chen ST, Zou W, Lin NT, Wu SH "A medically relevant capsular polysaccharide in Acinetobacter baumannii is a potential vaccine candidate" - Vaccine 35(10) (2017) 1440-1447
  

  Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection.

  Acinetobacter baumannii, capsular polysaccharide, Clinic population distribution, Passive immunity

  NCBI PubMed ID: 28190743
  Publication DOI: 10.1016/j.vaccine.2017.01.060
  Journal NLM ID: 8406899
  Publisher: Elsevier
  Correspondence: shwu@gate.sinica.edu.tw
  Institutions: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, National Health Research Institutes, Miaoli County 35053, Taiwan, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan, Human Health Therapeutics, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A0R, Canada, Institute of Microbiology, Tzu Chi University, Hualien 907, Taiwan
  Methods: 13C NMR, 1H NMR, methylation, NMR-2D, GC-MS, sugar analysis, acid hydrolysis, MS/MS, serological methods, enzymatic digestion, statistical analysis, SEC, immunization, conjugation, pulsed-field gel electrophoresis (PFGE)
  
   
  
  Acinetobacter baumannii SK44, Acinetobacter baumannii ATCC 17978, Acinetobacter baumannii SMAL, Acinetobacter baumannii ATCC 17961, Acinetobacter baumannii LUH5537
  CSDB ID 11986 (all data & tools)
• Article ID: 5500
  Singh JK, Adams FG, Brown MH "Diversity and Function of Capsular Polysaccharide in Acinetobacter baumannii" - Frontiers in Microbiology 9 (2019) 3301
  

  The Gram-negative opportunistic bacterium Acinetobacter baumannii is a significant cause of hospital-borne infections worldwide. Alarmingly, the rapid development of antimicrobial resistance coupled with the remarkable ability of isolates to persist on surfaces for extended periods of time has led to infiltration of A. baumannii into our healthcare environments. A major virulence determinant of A. baumannii is the presence of a capsule that surrounds the bacterial surface. This capsule is comprised of tightly packed repeating polysaccharide units which forms a barrier around the bacterial cell wall, providing protection from environmental pressures including desiccation and disinfection regimes as well as host immune responses such as serum complement. Additionally, capsule has been shown to confer resistance to a range of clinically relevant antimicrobial compounds. Distressingly, treatment options for A. baumannii infections are becoming increasingly limited, and the urgency to develop effective infection control strategies and therapies to combat infections is apparent. An increased understanding of the contribution of capsule to the pathobiology of A. baumannii is required to determine its feasibility as a target for new strategies to combat drug resistant infections. Significant variation in capsular polysaccharide structures between A. baumannii isolates has been identified, with over 100 distinct capsule types, incorporating a vast variety of sugars. This review examines the studies undertaken to elucidate capsule diversity and advance our understanding of the role of capsule in A. baumannii pathogenesis.

  polysaccharide, Acinetobacter, Acinetobacter baumannii, capsule, virulence factor, persistence

  NCBI PubMed ID: 30687280
  Publication DOI: 10.3389/fmicb.2018.03301
  Journal NLM ID: 101548977
  Publisher: Lausanne: Frontiers Research Foundation
  Correspondence: Melissa H. Brown
  Institutions: College of Science and Engineering, Flinders University, Bedford Park, SA, Australia.College of Science and Engineering, Flinders University, Bedford Park, SA, Australia
  
   
  
  Acinetobacter baumannii K3 ATCC 17978
  CSDB ID 2303 (all data & tools)
• Article ID: 5791
  Knirel YA, Van Calsteren M "Bacterial exopolysaccharides" - Book: Comprehensive Glycoscience: From Chemistry to Systems Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering (2021) 1-75
  

  Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.

  polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component

  Publication DOI: 10.1016/B978-0-12-819475-1.00005-5
  Publisher: Elsevier
  Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
  Editors: Barchi J, Kamerling H
  Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada
  
   
  
  Acinetobacter baumannii K3 ATCC 17978, Acinetobacter baumannii K3 SMAL, Acinetobacter baumannii K3 SK44
  CSDB ID 6708 (all data & tools)
• Article ID: 6148
  Talyansky Y, Nielsen TB, Yan J, Carlino-Macdonald U, Di Venanzio G, Chakravorty S, Ulhag A, Russo TA, Vinogradov E, Luna B, Wright MS, Adams MD, Spellberg B "Capsule carbohydrate structure determines virulence in Acinetobacter baumannii" - PLoS Pathogens 17(2) (2021) e1009291
  

  Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis.

  virulence, Acinetobacter baumannii, capsule, carbohydrate structure

  NCBI PubMed ID: 33529209
  Publication DOI: 10.1371/journal.ppat.1009291
  Journal NLM ID: 101238921
  Publisher: San Francisco, CA: Public Library of Science
  Correspondence: Brad Spellberg
  Institutions: Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, United States of America, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, United States of America, Division of Infectious Diseases, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Veterans Administration, Buffalo, New York, United States of America, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America, National Research Council Canada, Human Health Therapeutics Centre, Ottawa, Canada, Rady Children's Institute for Genomic Medicine, San Diego, California, United States of America, The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America, LAC+USC Medical Center, Los Angeles, California, United States of America
  Methods: PCR, genetic methods, RNA sequencing, flow cytometry, phagocytosis assay, mutant generation, genome BLAST analysis
  
   
  
  Acinetobacter baumannii ATCC 17978 (KL3), Acinetobacter baumannii ATCC 17978 Δgtr6/pSC1a, Acinetobacter baumannii NIH1 (KL3), Acinetobacter baumannii 15827 (KL22), Acinetobacter baumannii HUMC1::gtr6 (KL22)
  CSDB ID 9786 (all data & tools)