Found 6 structures.
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1. Compound ID: 11622
Structure type: polymer chemical repeating unit
Compound class: CPS, EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 4688
Kenyon JJ, Marzaioli AM, Hall RM, De Castro C "Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter baumannii" -
Glycobiology 24(6) (2014) 554-563
The repeat unit structure of the K2 capsule from an extensively antibiotic-resistant Acinetobacter baumannii global clone 2 (GC2) strain was determined. The oligosaccharide contains three simple sugars, d-glucopyranose, d-galatopyranose and N-acetyl-d-galactosamine, and the complex sugar, 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-non-2-ulosonic acid (Pse5Ac7Ac or pseudaminic acid), which has not previously been reported in any A. baumannii capsule. The strain was found to carry all the genes required for the synthesis of the sugars and construction of the K2 structure. The linkages catalyzed by the initiating transferase, three glycosyltransferases and the Wzy polymerase were also predicted. Examination of publicly available A. baumannii genome sequences revealed that the same gene cluster, KL2, often occurs in extensively antibiotic-resistant GC2 isolates and in further strain types. The gene module responsible for the synthesis of pseudaminic acid was also detected in four other K loci. A related module including genes for an acylated relative of pseudaminic acid was also found in two new KL types. A polymerase chain reaction scheme was developed to detect all modules containing genes for sugars based on pseudaminic acid and to specifically detect KL2.
Acinetobacter baumannii, capsule polysaccharide, K locus, global clone 2, K2
NCBI PubMed ID: 24688093Publication DOI: 10.1093/glycob/cwu024Journal NLM ID: 9104124Publisher: IRL Press at Oxford University Press
Correspondence: ruth.hall@sydney.edu.au
Institutions: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia
Methods: 13C NMR, 1H NMR, methylation, NMR-2D, PCR, GC-MS, sugar analysis, mild acid hydrolysis, chemical methods, genetic methods, bioinformatic analysis
- Article ID: 4721
Senchenkova SN, Shashkov AS, Shneider MM, Arbatsky NP, Popova AV, Miroshnikov KA, Volozhantsev NV, Knirel YA "Structure of the capsular polysaccharide of Acinetobacter baumannii ACICU containing di-N-acetylpseudaminic acid" -
Carbohydrate Research 391 (2014) 89-92
Capsular polysaccharide was isolated by the phenol-water extraction of Acinetobacter baumannii ACICU cells and studied by sugar analysis, partial acid hydrolysis, and 1D and 2D (1)H and (13)C NMR spectroscopy. The polysaccharide was found to contain 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno-non-2-ulosonic or di-N-acetylpseudaminic acid (Pse5Ac7Ac), and the following structure of the branched tetrasaccharide repeating unit was established: The genes present in the polysaccharide gene cluster of A. baumannii ACICU are appropriate to the structure established.
Acinetobacter baumannii, pseudaminic acid, capsular polysaccharide structure, polysaccharide gene cluster
NCBI PubMed ID: 24785392Publication DOI: 10.1016/j.carres.2014.04.002Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: Y.A. Knirel
Institutions: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, M. M. Shemyakin & Y. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia, State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russia
Methods: 13C NMR, 1H NMR, NMR-2D, GLC, mild acid hydrolysis, chemical methods, NMR-1D, GPC
- Article ID: 5016
Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, Huang KF, Wu SH "Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein" -
Scientific Reports 7 (2017) 42711
With an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage PhiAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The PhiAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-A resolution crystal structures of an N-terminally-truncated PhiAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric beta-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for PhiAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection.
Acinetobacter baumannii, pseudaminic acid, crystal structure, bacteriophage, glycoconjugate vaccine, Tailspike
NCBI PubMed ID: 28209973Publication DOI: 10.1038/srep42711Journal NLM ID: 101563288Publisher: London: Nature Publishing Group
Correspondence: huangkf@gate.sinica.edu.tw; shwu@gate.sinica.edu.tw
Institutions: Master program in Microbiology and Immunology, Tzu Chi University, Hualien 970, Taiwan, Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Core Facilities for Protein Structural Analysis (CFPSA), Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, gel filtration, NMR-2D, X-ray, SDS-PAGE, DNA techniques, crystallization, LC-ESI-MS, LC-ESI-MS/MS, enzyme kinetic assay, bacteriophage digestion, substrate binding
- Article ID: 5178
Lee IM, Yang FL, Chen TL, Liao KS, Ren CT, Lin NT, Chang YP, Wu CY, Wu SH "Pseudaminic acid on exopolysaccharide of Acinetobacter baumannii plays a critical role in phage-assisted preparation of glycoconjugate vaccine with high antigenicity" -
Journal of the American Chemical Society 140(28) (2018) 8639-8643
Pseudaminic acid (Pse) has been known for participating in crucial bacterial virulence and thus is an attractive target in the development of glycoconjugate vaccine. Particularly, this therapeutic alternative was suggested to be a potential solution against antibiotic resistant Acinetobacter baumannii that poses a serious global health threat. Also, Pse was found to be involved in the exopolysaccharide (EPS) of mild antibiotic resistant Acinetobacter baumannii strain 54149 (Ab-54149) of which specific glycosyl linkage can be depolymerized by phagePhiAB6 tailspike protein (PhiAB6TSP). In this study, we found that the antibodies induced by Ab-54149 EPS was capable of recognizing a range of EPS of other clinical A. baumannii strains, and deemed as a great potential material for vaccination. To efficiently acquire homogeneous EPS-derived oligosaccharide with significant immunogenic activity for the production of glycoconjugate, we used the PhiAB6TSP for the fragmentation of Ab-54149 EPS instead of chemical methods. Moreover, insight into the ligand binding characterization of PhiAB6TSP suggested the branched Pse on the Ab-54149 EPS served as a recognition site of PhiAB6TSP. The serum boosted by PhiAB6TSP-digested product and carrier protein CRM197 conjugate complex displayed specific sensitivity toward Ab-54149 EPS with bacterial killing activity. Strikingly, Pse is an ideal epitope with strong antigenicity, profiting the application of the probe for pathogen detection and glyco-based vaccine.
Acinetobacter baumannii, pseudaminic acid, exopolysaccharide, vaccine, CRM197, glycoconjugate vaccine
NCBI PubMed ID: 29965749Publication DOI: 10.1021/jacs.8b04078Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: shwu@gate.sinica.edu.tw; cyiwu@gate.sinica.edu.tw
Institutions: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Graduate Institute of Life Science, National Defense Medical Center, Taipei 112, Taiwan, Department of Microbiology , Tzu Chi University, Hualien 970, Taiwan, Department of Chemistry , National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, dot immunoblotting, ESI-MS, ESI-MS/MS, MALDI-TOF MS, STD NMR, extraction, serum bactericidal assays, conjugation, flow cytometry analysis, enzyme kinetic assay, bacteriophage digestion, substrate binding
- Article ID: 6211
Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" -
Chemical Reviews 122(20) (2022) 15672-15716
Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.
carbohydrates, glycan, glycoconjugate vaccine
NCBI PubMed ID: 35608633Publication DOI: 10.1021/acs.chemrev.2c00021Journal NLM ID: 2985134RPublisher: Chem Rev
Correspondence: J. Codée
; R. Adamo
Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
- Article ID: 6469
Sun K, Lian M, Li Q, Wang R, Gu Y, Lei P, He H, Xu H, Sha F, Sun L "Characterization of a novel exopolysaccharide from Acinetobacter rhizosphaerae with ability to enhance the salt stress resistance of rice seedlings" -
International Journal of Biological Macromolecules (2023) 128438
We here describe the isolation of a novel exopolysaccharide from Acinetobacter rhizosphaerae, named ArEPS. The structure of ArEPS was characterized by analysis of the monosaccharide composition, molecular weight, infrared spectrum, methylation, and nuclear magnetic resonance spectrum. ArEPS was found to be an acidic heteropolysaccharide composed of glucose, galactose, galacturonic acid, glucuronic acid, mannose, and glucosamine; the molecular weight was 1533 kDa. Structural analysis showed that the main-chain structure of ArEPS predominantly comprised 1,3,6-β-Glcp, 1,3,4-α-Galp, 1,2-β-Glcp, 1,4-β-GlcpA, 1,4-β-GalpA, and the side-chain structure comprised 1,6-β-Glcp, 1,3-β-Galp, 1-α-Glcp, 1-β-Galp, 1-α-Manp, 1,4,6-α-Glcp, 1,2,4-β-Glcp, 1,2,3-β-Glcp, and 1,3-β-GlcpN. ArEPS significantly enhanced the tolerance of rice seedlings to salt stress. Specifically, plant height, fresh weight, chlorophyll content, and the K+/Na+ ratio increased by 51 %, 63 %, 29 %, and 162 %, respectively, and the malondialdehyde content was reduced by 45 % after treatment with 100 mg/kg ArEPS compared to treatment with 100 mM NaCl. Finally, based on the quadratic regression between fresh weight and ArEPS addition, the optimal ArEPS addition level was estimated to be 135.12 mg/kg. These results indicate the prospects of ArEPS application in agriculture.
exopolysaccharides, Structural characterization, salt stress alleviation
NCBI PubMed ID: 38042318Publication DOI: 10.1016/j.ijbiomac.2023.128438Journal NLM ID: 7909578Publisher: Butterworth-Heinemann
Correspondence: F. Sha
; L. Sun
Institutions: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, China, Suzhou Cornigs Polyols CO., LTD., Suzhou 215000, China, Westa College, Southwest University, Chongqing 400715, China, School of Chemical Biology & Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
Methods: 13C NMR, 1H NMR, NMR-2D, GC-MS, FTIR, composition analysis, HPLC, statistical analysis, salt stress, HPGFC-MALLS-RI
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2. Compound ID: 12617
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-+
|
-3)-b-D-GalpNAc-(1-3)-b-D-Galp-(1- |
Show graphically |
Structure type: polymer chemical repeating unit
Compound class: EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 5016
Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, Huang KF, Wu SH "Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein" -
Scientific Reports 7 (2017) 42711
With an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage PhiAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The PhiAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-A resolution crystal structures of an N-terminally-truncated PhiAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric beta-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for PhiAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection.
Acinetobacter baumannii, pseudaminic acid, crystal structure, bacteriophage, glycoconjugate vaccine, Tailspike
NCBI PubMed ID: 28209973Publication DOI: 10.1038/srep42711Journal NLM ID: 101563288Publisher: London: Nature Publishing Group
Correspondence: huangkf@gate.sinica.edu.tw; shwu@gate.sinica.edu.tw
Institutions: Master program in Microbiology and Immunology, Tzu Chi University, Hualien 970, Taiwan, Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Core Facilities for Protein Structural Analysis (CFPSA), Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, gel filtration, NMR-2D, X-ray, SDS-PAGE, DNA techniques, crystallization, LC-ESI-MS, LC-ESI-MS/MS, enzyme kinetic assay, bacteriophage digestion, substrate binding
- Article ID: 5178
Lee IM, Yang FL, Chen TL, Liao KS, Ren CT, Lin NT, Chang YP, Wu CY, Wu SH "Pseudaminic acid on exopolysaccharide of Acinetobacter baumannii plays a critical role in phage-assisted preparation of glycoconjugate vaccine with high antigenicity" -
Journal of the American Chemical Society 140(28) (2018) 8639-8643
Pseudaminic acid (Pse) has been known for participating in crucial bacterial virulence and thus is an attractive target in the development of glycoconjugate vaccine. Particularly, this therapeutic alternative was suggested to be a potential solution against antibiotic resistant Acinetobacter baumannii that poses a serious global health threat. Also, Pse was found to be involved in the exopolysaccharide (EPS) of mild antibiotic resistant Acinetobacter baumannii strain 54149 (Ab-54149) of which specific glycosyl linkage can be depolymerized by phagePhiAB6 tailspike protein (PhiAB6TSP). In this study, we found that the antibodies induced by Ab-54149 EPS was capable of recognizing a range of EPS of other clinical A. baumannii strains, and deemed as a great potential material for vaccination. To efficiently acquire homogeneous EPS-derived oligosaccharide with significant immunogenic activity for the production of glycoconjugate, we used the PhiAB6TSP for the fragmentation of Ab-54149 EPS instead of chemical methods. Moreover, insight into the ligand binding characterization of PhiAB6TSP suggested the branched Pse on the Ab-54149 EPS served as a recognition site of PhiAB6TSP. The serum boosted by PhiAB6TSP-digested product and carrier protein CRM197 conjugate complex displayed specific sensitivity toward Ab-54149 EPS with bacterial killing activity. Strikingly, Pse is an ideal epitope with strong antigenicity, profiting the application of the probe for pathogen detection and glyco-based vaccine.
Acinetobacter baumannii, pseudaminic acid, exopolysaccharide, vaccine, CRM197, glycoconjugate vaccine
NCBI PubMed ID: 29965749Publication DOI: 10.1021/jacs.8b04078Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: shwu@gate.sinica.edu.tw; cyiwu@gate.sinica.edu.tw
Institutions: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Graduate Institute of Life Science, National Defense Medical Center, Taipei 112, Taiwan, Department of Microbiology , Tzu Chi University, Hualien 970, Taiwan, Department of Chemistry , National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, dot immunoblotting, ESI-MS, ESI-MS/MS, MALDI-TOF MS, STD NMR, extraction, serum bactericidal assays, conjugation, flow cytometry analysis, enzyme kinetic assay, bacteriophage digestion, substrate binding
- Article ID: 6211
Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" -
Chemical Reviews 122(20) (2022) 15672-15716
Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.
carbohydrates, glycan, glycoconjugate vaccine
NCBI PubMed ID: 35608633Publication DOI: 10.1021/acs.chemrev.2c00021Journal NLM ID: 2985134RPublisher: Chem Rev
Correspondence: J. Codée
; R. Adamo
Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
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3. Compound ID: 12618
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-+
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-b-D-Galp-(1-3)-b-D-GalpNAc-(1-3)-b-D-Galp-(1-3)-D-GalpNAc |
Show graphically |
Structure type: oligomer
; 1727.6364
Compound class: EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_1391961,IEDB_1391963,IEDB_141584,IEDB_141794,IEDB_142488,IEDB_143260,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_885822,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 5016
Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, Huang KF, Wu SH "Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein" -
Scientific Reports 7 (2017) 42711
With an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage PhiAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The PhiAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-A resolution crystal structures of an N-terminally-truncated PhiAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric beta-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for PhiAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection.
Acinetobacter baumannii, pseudaminic acid, crystal structure, bacteriophage, glycoconjugate vaccine, Tailspike
NCBI PubMed ID: 28209973Publication DOI: 10.1038/srep42711Journal NLM ID: 101563288Publisher: London: Nature Publishing Group
Correspondence: huangkf@gate.sinica.edu.tw; shwu@gate.sinica.edu.tw
Institutions: Master program in Microbiology and Immunology, Tzu Chi University, Hualien 970, Taiwan, Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Core Facilities for Protein Structural Analysis (CFPSA), Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, gel filtration, NMR-2D, X-ray, SDS-PAGE, DNA techniques, crystallization, LC-ESI-MS, LC-ESI-MS/MS, enzyme kinetic assay, bacteriophage digestion, substrate binding
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4. Compound ID: 12619
|
b-D-Glcp-(1-6)-+
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-b-D-Galp-(1-3)-b-D-GalpNAc-(1-3)-b-D-Galp-(1-3)-D-GalpNAc |
Show graphically |
Structure type: oligomer
; 1410.69123
Compound class: EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_1391961,IEDB_1391963,IEDB_141584,IEDB_141794,IEDB_142488,IEDB_143260,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_885822,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 5016
Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, Huang KF, Wu SH "Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein" -
Scientific Reports 7 (2017) 42711
With an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage PhiAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The PhiAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-A resolution crystal structures of an N-terminally-truncated PhiAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric beta-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for PhiAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection.
Acinetobacter baumannii, pseudaminic acid, crystal structure, bacteriophage, glycoconjugate vaccine, Tailspike
NCBI PubMed ID: 28209973Publication DOI: 10.1038/srep42711Journal NLM ID: 101563288Publisher: London: Nature Publishing Group
Correspondence: huangkf@gate.sinica.edu.tw; shwu@gate.sinica.edu.tw
Institutions: Master program in Microbiology and Immunology, Tzu Chi University, Hualien 970, Taiwan, Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Core Facilities for Protein Structural Analysis (CFPSA), Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, gel filtration, NMR-2D, X-ray, SDS-PAGE, DNA techniques, crystallization, LC-ESI-MS, LC-ESI-MS/MS, enzyme kinetic assay, bacteriophage digestion, substrate binding
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5. Compound ID: 13061
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-+
|
b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-b-D-Galp-(1-3)-b-D-GalpNAc-(1-3)-b-D-Galp-(1-3)-D-GalpNAc |
Show graphically |
Structure type: oligomer
Compound class: EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_1391961,IEDB_1391963,IEDB_141584,IEDB_141794,IEDB_142488,IEDB_143260,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_885822,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 5178
Lee IM, Yang FL, Chen TL, Liao KS, Ren CT, Lin NT, Chang YP, Wu CY, Wu SH "Pseudaminic acid on exopolysaccharide of Acinetobacter baumannii plays a critical role in phage-assisted preparation of glycoconjugate vaccine with high antigenicity" -
Journal of the American Chemical Society 140(28) (2018) 8639-8643
Pseudaminic acid (Pse) has been known for participating in crucial bacterial virulence and thus is an attractive target in the development of glycoconjugate vaccine. Particularly, this therapeutic alternative was suggested to be a potential solution against antibiotic resistant Acinetobacter baumannii that poses a serious global health threat. Also, Pse was found to be involved in the exopolysaccharide (EPS) of mild antibiotic resistant Acinetobacter baumannii strain 54149 (Ab-54149) of which specific glycosyl linkage can be depolymerized by phagePhiAB6 tailspike protein (PhiAB6TSP). In this study, we found that the antibodies induced by Ab-54149 EPS was capable of recognizing a range of EPS of other clinical A. baumannii strains, and deemed as a great potential material for vaccination. To efficiently acquire homogeneous EPS-derived oligosaccharide with significant immunogenic activity for the production of glycoconjugate, we used the PhiAB6TSP for the fragmentation of Ab-54149 EPS instead of chemical methods. Moreover, insight into the ligand binding characterization of PhiAB6TSP suggested the branched Pse on the Ab-54149 EPS served as a recognition site of PhiAB6TSP. The serum boosted by PhiAB6TSP-digested product and carrier protein CRM197 conjugate complex displayed specific sensitivity toward Ab-54149 EPS with bacterial killing activity. Strikingly, Pse is an ideal epitope with strong antigenicity, profiting the application of the probe for pathogen detection and glyco-based vaccine.
Acinetobacter baumannii, pseudaminic acid, exopolysaccharide, vaccine, CRM197, glycoconjugate vaccine
NCBI PubMed ID: 29965749Publication DOI: 10.1021/jacs.8b04078Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: shwu@gate.sinica.edu.tw; cyiwu@gate.sinica.edu.tw
Institutions: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Graduate Institute of Life Science, National Defense Medical Center, Taipei 112, Taiwan, Department of Microbiology , Tzu Chi University, Hualien 970, Taiwan, Department of Chemistry , National Taiwan University, Taipei 106, Taiwan
Methods: 13C NMR, 1H NMR, dot immunoblotting, ESI-MS, ESI-MS/MS, MALDI-TOF MS, STD NMR, extraction, serum bactericidal assays, conjugation, flow cytometry analysis, enzyme kinetic assay, bacteriophage digestion, substrate binding
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6. Compound ID: 16048
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b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-+
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b-Psep5Ac7Ac-(2-6)-b-D-Glcp-(1-6)-b-D-Galp-(1-3)-b-D-GalpNAc-(1-3)-b-D-Galp-(1-3)-b-D-GalpNAc-(1--/spacer-CRM197/ |
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Structure type: oligomer
Aglycon: spacer-CRM197
Trivial name: repeating unit conjugate
Compound class: EPS
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_147450,IEDB_190606,IEDB_983931,SB_165,SB_166,SB_187,SB_192,SB_195,SB_21,SB_23,SB_24,SB_7,SB_8,SB_88
The structure is contained in the following publication(s):
- Article ID: 6211
Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" -
Chemical Reviews 122(20) (2022) 15672-15716
Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.
carbohydrates, glycan, glycoconjugate vaccine
NCBI PubMed ID: 35608633Publication DOI: 10.1021/acs.chemrev.2c00021Journal NLM ID: 2985134RPublisher: Chem Rev
Correspondence: J. Codée
; R. Adamo
Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
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