Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: nosocomial infections [ICD11:
XB25 
];
urinary tract infections (UTI) [ICD11:
GC08 
];
infection due to Klebsiella pneumoniae [ICD11:
XN741 
]
NCBI PubMed ID: 28815890Publication DOI: 10.1002/anie.201700964Journal NLM ID: 0370543Publisher: Weinheim: Wiley-VCH
Correspondence: peter.seeberger

mpikg.mpg.de; claney.pereira

vaxxilon.com
Institutions: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14424, Potsdam, Germany, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany, Department of Medicine, Division of Infectious Diseases, Stony Brook University, 101 Nicolls Road, Stony Brook, NY, 11794, USA, Charité-Universitätsmedizin Berlin, Department of Infectious Diseases and Pulmonary Medicine, Charitéplatz 1, 10117, Berlin, Germany
Hospital-acquired infections are an increasingly serious health concern. Infections caused by carpabenem-resistant Klebsiella pneumoniae (CR-Kp) are especially problematic, with a 50 % average survival rate. CR-Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross-reactive antibodies against CR-Kp CPS in mice and rabbits. Whole-cell ELISA was used to establish the surface staining of CR-Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi-synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium.
vaccines, Klebsiella pneumoniae, antibiotic resistance, hexasaccharide total synthesis
Structure type: polymer chemical repeating unit
Location inside paper: p.13974, fig.1A
Compound class: CPS
Contained glycoepitopes: IEDB_133754,IEDB_136044,IEDB_136105,IEDB_137472,IEDB_141794,IEDB_144825,IEDB_190606,IEDB_225177,IEDB_885823,SB_165,SB_166,SB_187,SB_195,SB_7,SB_88
Methods: 13C NMR, 1H NMR, TLC, ELISA, ESI-MS, chemical synthesis, MALDI-TOF MS, UV, glycosylation, optical rotation measurement, binding assays, immunization, conjugation
Comments, role: structure CPS isolated from carpabenem-resistant Klebsiella pneumoniae (CR-Kp) from ref [17]. Published polymerization frame was shifted for conformity with other records.
NCBI Taxonomy refs (TaxIDs): 573Reference(s) to other database(s): GTC:G57429IZ
Show glycosyltransferases
There is only one chemically distinct structure: