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Richard G, MacKenzie CR, Henry KA, Vinogradov E, Hall JC, Hussack G
Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth
Antimicrobial Agents and Chemotherapy 64(4) (2020)
e02168
|
-4)-b-D-ManpNAc3NAmA-(1-4)-b-D-ManpNAc3NAcA-(1-3)-a-D-FucpNAc-(1- |
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Pseudomonas aeruginosa O5 PAO1
(NCBI TaxID 208964,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Pseudomonas aeruginosa [ICD11:
XN5L6 
]
NCBI PubMed ID: 32015038Publication DOI: 10.1128/AAC.02168-19Journal NLM ID: 0315061Correspondence: Greg.Hussack
nrc-cnrc.gc.ca
Institutions: School of Environmental Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada K1A 0R6
Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O-antigen of a second lipopolysaccharide type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.
Lipopolysaccharide, LPS, AFM, atomic force microscopy, antibacterial antibodies, O-specific antigen, outer membrane disruption
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1a, O5 (PAO1)
Trivial name: B band polysaccharide, B-band polysaccharide
Compound class: O-polysaccharide, O-antigen
Methods: ELISA, serological methods, SPR, AFM, antibody sequence analyses
Related record ID(s): 6488, 6489, 32188
NCBI Taxonomy refs (TaxIDs): 208964Reference(s) to other database(s): GlycomeDB:
33661
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Richard G, MacKenzie CR, Henry KA, Vinogradov E, Hall JC, Hussack G
Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth
Antimicrobial Agents and Chemotherapy 64(4) (2020)
e02168
|
-3)-a-L-Rhap-(1-4)-a-D-GalpNAcA3Ac6NH2-(1-4)-a-D-GalpNFoA6(40%)NH2-(1-3)-b-D-QuipNAc-(1- |
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Pseudomonas aeruginosa O6a,6d
(Ancestor NCBI TaxID 287,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Pseudomonas aeruginosa [ICD11:
XN5L6 ]
NCBI PubMed ID: 32015038Publication DOI: 10.1128/AAC.02168-19Journal NLM ID: 0315061Correspondence: Greg.Hussack
nrc-cnrc.gc.ca
Institutions: School of Environmental Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada K1A 0R6
Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O-antigen of a second lipopolysaccharide type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.
Lipopolysaccharide, LPS, AFM, atomic force microscopy, antibacterial antibodies, O-specific antigen, outer membrane disruption
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1a, O6a,6d
Compound class: O-antigen
Contained glycoepitopes: IEDB_136105,IEDB_225177,IEDB_885823
Methods: ELISA, serological methods, SPR, AFM, antibody sequence analyses
Related record ID(s): 6487, 6489, 32188
NCBI Taxonomy refs (TaxIDs): 287Reference(s) to other database(s): GTC:G02697KO
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There is only one chemically distinct structure:
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Richard G, MacKenzie CR, Henry KA, Vinogradov E, Hall JC, Hussack G
Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth
Antimicrobial Agents and Chemotherapy 64(4) (2020)
e02168
|
-4)-a-D-GalpNAcA3Ac6NH2-(1-4)-a-D-GalpNFoA6NH2-(1-3)-a-D-QuipNAc-(1-2)-a-L-Rhap-(1- |
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Pseudomonas aeruginosa Fisher 1
(Ancestor NCBI TaxID 287,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Pseudomonas aeruginosa [ICD11:
XN5L6 ]
NCBI PubMed ID: 32015038Publication DOI: 10.1128/AAC.02168-19Journal NLM ID: 0315061Correspondence: Greg.Hussack
nrc-cnrc.gc.ca
Institutions: School of Environmental Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada K1A 0R6
Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O-antigen of a second lipopolysaccharide type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.
Lipopolysaccharide, LPS, AFM, atomic force microscopy, antibacterial antibodies, O-specific antigen, outer membrane disruption
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1a, Fisher 1
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_136105,IEDB_225177,IEDB_885823
Methods: ELISA, serological methods, SPR, AFM, antibody sequence analyses
Comments, role: published polymerization frame was shifted for conformity with other records.
Related record ID(s): 6487, 6488, 32188
NCBI Taxonomy refs (TaxIDs): 287Reference(s) to other database(s): GTC:G36772HX, GlycomeDB:
25506
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Richard G, MacKenzie CR, Henry KA, Vinogradov E, Hall JC, Hussack G
Antibody Binding to the O-Specific Antigen of Pseudomonas aeruginosa O6 Inhibits Cell Growth
Antimicrobial Agents and Chemotherapy 64(4) (2020)
e02168
|
-4)-a-D-GalpNAcA3Ac6NH2-(1-4)-a-D-GalpNFoA-(1-3)-a-D-QuipNAc-(1-3)-a-L-Rhap-(1- |
Show graphically |
Pseudomonas aeruginosa O6 (O6 IATS)
(Ancestor NCBI TaxID 287,
species name lookup)
Pseudomonas aeruginosa PAK
(NCBI TaxID 1009714,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Pseudomonas aeruginosa [ICD11:
XN5L6 ]
NCBI PubMed ID: 32015038Publication DOI: 10.1128/AAC.02168-19Journal NLM ID: 0315061Correspondence: Greg.Hussack
nrc-cnrc.gc.ca
Institutions: School of Environmental Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5, Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON, Canada K1A 0R6
Pseudomonas aeruginosa is an opportunistic pathogen that is inherently resistant to many antibiotics and represents an increasing threat due to the emergence of drug-resistant strains. There is a pressing need to develop innovative antimicrobials against this pathogen. In this study we identified the O-specific antigen (OSA) of P. aeruginosa serotype O6 as a novel target for therapeutic intervention. Binding of monoclonal antibodies and antigen-binding fragments therefrom to O6 OSA leads to rapid outer membrane destabilization and inhibition of cell growth. The antimicrobial effect correlated directly with antibody affinity. Antibody binding to the O-antigen of a second lipopolysaccharide type present in P. aeruginosa or to the LPS core did not affect cell viability. Atomic force microscopy showed that antibody binding to OSA resulted in early flagellum loss, formation of membrane blebs, and eventually complete outer membrane loss. We hypothesize that antibody binding to OSA disrupts a key interaction in the P. aeruginosa outer membrane.
Lipopolysaccharide, LPS, AFM, atomic force microscopy, antibacterial antibodies, O-specific antigen, outer membrane disruption
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1a, O6 IATS, PAK
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_136105,IEDB_225177,IEDB_885823
Methods: ELISA, serological methods, SPR, AFM, antibody sequence analyses
Comments, role: published polymerization frame was shifted for conformity with other records.
Related record ID(s): 6487, 6488, 6489
NCBI Taxonomy refs (TaxIDs): 287,
1009714Reference(s) to other database(s): GTC:G72106LC, GlycomeDB:
37362
Show glycosyltransferases
There is only one chemically distinct structure:
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