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1. (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: 33529209Publication DOI: 10.1371/journal.ppat.1009291Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: Brad Spellberg
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
Methods: PCR, genetic methods, RNA sequencing, flow cytometry, phagocytosis assay, mutant generation, genome BLAST analysis
The publication contains the following compound(s):
- Compound ID: 15879
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b-D-GlcpNAc3NAcA4(%)Ac-(1-4)-+
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-3)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1- |
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Structure type: polymer chemical repeating unit
Trivial name: O-glycan
Compound class: CPS
- Compound ID: 11322
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b-D-GlcpNAc3NAcA4Ac-(1-4)-+
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-3)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1-
|
b-D-GlcpNAc-(1-6)-+ |
Show graphically |
Structure type: polymer chemical repeating unit
Trivial name: O-glycan
Compound class: CPS
Reference(s) to other database(s): GTC:G64997NS
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