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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
|
b-D-GlcpNAc3NAcA4Ac-(1-4)-+
|
-3)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1-
|
b-D-GlcpNAc-(1-6)-+ |
Show graphically |
Acinetobacter baumannii ATCC 17978 (KL3)
(NCBI TaxID 400667,
species name lookup)
Acinetobacter baumannii ATCC 17978 Δgtr6/pSC1a
(Ancestor NCBI TaxID 400667,
species name lookup)
Acinetobacter baumannii NIH1 (KL3)
(Ancestor NCBI TaxID 470,
species name lookup)
Acinetobacter baumannii 15827 (KL22)
(NCBI TaxID 1310631,
species name lookup)
Acinetobacter baumannii HUMC1::gtr6 (KL22)
(Ancestor NCBI TaxID 470,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Acinetobacter baumannii [ICD11:
XN8LS 
]
NCBI PubMed ID: 33529209Publication DOI: 10.1371/journal.ppat.1009291Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: Brad Spellberg <bspellberg
dhs.lacounty.gov>
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
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
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1B (Bottom)
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
Methods: PCR, genetic methods, RNA sequencing, flow cytometry, phagocytosis assay, mutant generation, genome BLAST analysis
Comments, role: review
Related record ID(s): 10948
NCBI Taxonomy refs (TaxIDs): 400667,
470,
1310631Reference(s) to other database(s): GTC:G64997NS
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There is only one chemically distinct structure:
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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
|
b-D-GlcpNAc3NAcA4(%)Ac-(1-4)-+
|
-3)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1- |
Show graphically |
Acinetobacter baumannii ATCC 17978 Δgtr6 (KL3)
(Ancestor NCBI TaxID 400667,
species name lookup)
Acinetobacter baumannii NIH1 (KL3)
(Ancestor NCBI TaxID 470,
species name lookup)
Acinetobacter baumannii HUMC1 (KL22)
(Ancestor NCBI TaxID 470,
species name lookup)
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Acinetobacter baumannii [ICD11:
XN8LS ]
NCBI PubMed ID: 33529209Publication DOI: 10.1371/journal.ppat.1009291Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: Brad Spellberg <bspellberg
dhs.lacounty.gov>
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
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
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 1B (Top)
Trivial name: O-glycan
Compound class: CPS
Contained glycoepitopes: IEDB_130648,IEDB_136906,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_21,SB_7
Methods: PCR, genetic methods, RNA sequencing, flow cytometry, phagocytosis assay, mutant generation, genome BLAST analysis
Comments, role: 4-OAc - 90% for pgt1+ HUMC1 and 50% for pgt1- ATCC 17978 Δgtr6.
Related record ID(s): 9786
NCBI Taxonomy refs (TaxIDs): 400667,
470
Show glycosyltransferases
There is only one chemically distinct structure:
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