Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: pneumonia [ICD11:
CA40 
];
infection due to Acinetobacter baumannii [ICD11:
XN8LS ]
NCBI PubMed ID: 23297385Publication DOI: 10.1128/IAI.01184-12Journal NLM ID: 0246127Publisher: American Society for Microbiology
Correspondence: Thomas A. Russo <trusso
acsu.buffalo.edu>
Institutions: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada, Veterans Administration Western New York Healthcare System, University at Buffalo-State University of New York, Buffalo, New York, USA, Department of Medicine, University at Buffalo-State University of New York, Buffalo, New York, USA, Department of Microbiology and Immunology, University at Buffalo-State University of New York, Buffalo, New York, USA, The Witebsky Center for Microbial Pathogenesis, University at Buffalo-State University of New York, Buffalo, New York, USA, Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, USA
The emergence of extreme and pan-resistant gram-negative bacilli, such as Acinetobacter baumannii requires consideration of non-antimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and NMR techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody MAb13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb13D6. Opsonization of K1-positive strains, but not K1-minus strains, with MAb13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb13D6 three and twenty-four h after bacterial challenge in a rat soft-tissue infection model resulted in a significant decrease in the growth/survival a K1-positive strain compared to a K1-minus strain or to treatment with a vehicle control (P <0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment and pragmatic challenges exist such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
Acinetobacter baumannii, monoclonal antibodies, immunization, serotype-specific, capsular polysaccharid
Structure type: homopolymer
Location inside paper: p.917
Trivial name: poly-β-1,6-GlcNAc (PGA), biofilm, poly-b-(1-6)-N-acetyl-D-glucosamine (PNAG), poly-β-N-acetyl-glucosamine (PNAG), PNAG, poly-N-acetylglucosamine, PNAG
Compound class: CPS, EPS, O-polysaccharide, glucan, polysaccharide
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_753248
Methods: 13C NMR, 1H NMR, sugar analysis, biological assays, serological methods, CE-ESI-MS, statistical analysis, immunization
Related record ID(s): 29336
NCBI Taxonomy refs (TaxIDs): 470Reference(s) to other database(s): GTC:G36952FI, GlycomeDB:
11210
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There is only one chemically distinct structure:
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