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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

NCBI PubMed ID: 23297385
Publication DOI: 10.1128/IAI.01184-12
Journal NLM ID: 0246127
Publisher: American Society for Microbiology
Correspondence: Thomas A. Russo
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
Methods: 13C NMR, 1H NMR, sugar analysis, biological assays, serological methods, CE-ESI-MS, statistical analysis, immunization

Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines.Recent analysis from WHO/CHO underpins alarming concern towards antibiotic resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyses structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

carbohydrates, glycoconjugates, vaccines, glycoengineering, antimicrobial resistance

NCBI PubMed ID: 29547971
Publication DOI: 10.1093/femsre/fuy011
Journal NLM ID: 8902526
Publisher: Oxford University Press
Correspondence: Roberto Adamo
Institutions: GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena

Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.

polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component

Publication DOI: 10.1016/B978-0-12-819475-1.00005-5
Publisher: Elsevier
Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
Editors: Barchi J, Kamerling H
Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada