Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: infection due to Acinetobacter baumannii [ICD11:
XN8LS 
]
NCBI PubMed ID: 35980044Publication DOI: 10.1128/spectrum.01674-22Journal NLM ID: 101634614Publisher: Washington, DC: ASM Press
Correspondence: N.Rudenko <nrudkova
mail.ru>
Institutions: Laboratory of Immunochemistry, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, Russia, Laboratory of Carbohydrates and Biocides, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Laboratory of Molecular Bioengineering, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
The clonal bacterial species Acinetobacter baumannii is an emerging multidrug-resistant pathogen which causes high-lethality infections. Cells of A. baumannii are surrounded by the type-specific capsular polysaccharide (CPS), which provides resistance to the protective mechanisms of the host and is considered a target for immunization. The conjugates of three inert carrier proteins and A. baumannii type K9 CPS fragments, which contained various numbers of oligosaccharide repeats (K-units), were synthesized by periodate oxidation and squaric acid chemistry. The conjugates were applied to immunize mice, and chemical synthesis by squaric acid was shown to significantly improve the immunogenic properties of glycoconjugate. In BALB/c mice, IgG antibodies were predominant among type K9 CPS reactive antibodies, and their total content was several times higher than that of IgM. Immune sera were characterized by their opsonization ability during practically the entire lives of the experimental mice. The sera were cross-reactive, but the highest specificity was observed against the antigen (type K9 CPS) used for immunization. The immunization of BALB/c and ICR-1 mice with a glycoconjugate without adjuvants led to varying degrees of stimulation of IL-10, IL-17A, and TNF-alpha production, but not IL-4 production in the ICR-1 mice. This is in contrast to the BALB/c mice, in which gamma-IFN production was also activated. The protective effectiveness of the glycoconjugates obtained by squaric acid chemistry was demonstrated by experiments that involved challenging immunized and nonimmunized animals with a lethal dose of A. baumannii K9. IMPORTANCE Immunization by glycoconjugates with A. baumannii type K9 CPS fragments induced a high level of antibodies (predominantly IgG) in sera, which reacted specifically with the CPS of A. baumannii type K9, as well as a long immunological memory. The sera of immunized animals efficiently opsonized A. baumannii type K9. Immunization resulted in the balanced production of pro/anti-inflammatory lymphokines and protective antibodies to ensure the survival of the mice infected with A. baumannii. The level of specific antibodies was sufficient to provide protective immunity against the challenge by A. baumannii, making this approach applicable in the development of vaccine preparations.
carbohydrates, carbohydrate, Acinetobacter baumannii, capsular polysaccharide, glycoconjugate, immunochemistry, interleukins, opsonisation assay
Structure type: polymer chemical repeating unit
Location inside paper: Fig. 3, A. baumannii KZ-1093
Compound class: CPS
Contained glycoepitopes: IEDB_130648,IEDB_134624,IEDB_134627,IEDB_136044,IEDB_136906,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_142488,IEDB_146664,IEDB_147450,IEDB_151528,IEDB_190606,IEDB_742248,IEDB_983931,SB_163,SB_165,SB_166,SB_187,SB_192,SB_195,SB_23,SB_24,SB_25,SB_7,SB_8,SB_88
Methods: periodate oxidation, EIA, chemical synthesis, MALDI-TOF MS, statistical analysis, immunization, HR-ESI-MS, opsonization assay
Related record ID(s): 8543, 9188, 9189, 9191
NCBI Taxonomy refs (TaxIDs): 470Reference(s) to other database(s): GTC:G41835WJ
Show glycosyltransferases
There is only one chemically distinct structure:
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