A Vaccine Approach for the Prevention of Infections by Multidrug-resistant Enterococcus faecium
Autor: | Evgeny Vinogradov, Diana Laverde, Srinivas Kodali, Kathrin U. Jansen, Fiona L. Lin, Johannes Huebner, Annaliesa S. Anderson, C. Hal Jones, Vilo Pavliak, Li Hao, Robert G. K. Donald, Nancy Khoury |
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Rok vydání: | 2015 |
Předmět: |
Lipopolysaccharides
Glycoconjugate Enterococcus faecium carbohydrate structure Biochemistry Mice vaccine Drug Resistance Multiple Bacterial chemistry.chemical_classification biology Opsonin Proteins teichoic acid Antibodies Bacterial Anti-Bacterial Agents Bacterial vaccine Uronic Acids Carbohydrate Sequence Bacterial Vaccines Female Rabbits Lipoteichoic acid Antibody Molecular Sequence Data Microbiology antigen Bacterial Proteins Antigen Animals Humans Molecular Biology Gram-Positive Bacterial Infections Antiserum Antigens Bacterial Vaccines Conjugate Immune Sera Cell Biology biochemical phenomena metabolism and nutrition biology.organism_classification Bacterial Load Fructans Teichoic Acids Disease Models Animal chemistry Enterococcus Sialic Acids biology.protein bacteria |
Zdroj: | Journal of Biological Chemistry. 290:19512-19526 |
ISSN: | 0021-9258 |
Popis: | The incidence of multidrug-resistant Enterococcus faecium hospital infections has been steadily increasing. With the goal of discovering new vaccine antigens, we systematically fractionated and purified four distinct surface carbohydrates from E. faecium endocarditis isolate Tx16, shown previously to be resistant to phagocytosis in the presence of human serum. The two most abundant polysaccharides consist of novel branched heteroglycan repeating units that include signature sugars altruronic acid and legionaminic acid, respectively. A minor high molecular weight polysaccharide component was recognized as the fructose homopolymer levan, and a glucosylated lipoteichoic acid (LTA) was identified in a micellar fraction. The polysaccharides were conjugated to the CRM₁₉₇ carrier protein, and the resulting glycoconjugates were used to immunize rabbits. Rabbit immune sera were evaluated for their ability to kill Tx16 in opsonophagocytic assays and in a mouse passive protection infection model. Although antibodies raised against levan failed to mediate opsonophagocytic killing, the other glycoconjugates induced effective opsonic antibodies, with the altruronic acid-containing polysaccharide antisera showing the greatest opsonophagocytic assay activity. Antibodies directed against either novel heteroglycan or the LTA reduced bacterial load in mouse liver or kidney tissue. To assess antigen prevalence, we screened a diverse collection of blood isolates (n = 101) with antibodies to the polysaccharides. LTA was detected on the surface of 80% of the strains, and antigens recognized by antibodies to the two major heteroglycans were co-expressed on 63% of these clinical isolates. Collectively, these results represent the first steps toward identifying components of a glycoconjugate vaccine to prevent E. faecium infection. |
Databáze: | OpenAIRE |
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