A Vaccine Approach for the Prevention of Infections by Multidrug-resistant Enterococcus faecium

Kodali, Srinivas; Vinogradov, Evgeny; Lin, Fiona L.; Khoury, Nancy; Hao, Li; Pavliak, Vilo; Ca, Jones; Laverde, Diana; Hüebner, Johannes; Jansen, Kathrin U.; Anderson, Annaliesa S.; Donald, Robert G. K.

doi:10.1074/jbc.m115.655852

Cited by 38 publications

(20 citation statements)

References 66 publications

(65 reference statements)

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“…50 They are amongst the most prevalent nosocomial infectious agents and especially multi-drug resistant enterococci pose a great problem. 52 Our group The poly(glycerol phosphate) chain of these bacteria can be decorated with either D-alanine residues or carbohydrate appendages.…”

Section: Chemical Synthesis Of Tasmentioning

confidence: 99%

Teichoic acids: synthesis and applications

Hogendorf

Overkleeft

et al. 2017

Chem. Soc. Rev.

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This review describes the developments in the synthesis of teichoic acids (TA) - glycosylated poly(alditolphosphates) - and the application of these fragments in immunological studies. These structurally diverse biopolymers are omnipresent constituents of the Gram-positive bacterial cell wall where they fulfill a variety of vital functions. They have been and continue to be attractive synthetic targets because of their challenging structures and the fact that their microheterogeneity precludes their isolation in single and pure enough form from natural sources. Progress in glycosylation chemistry and the development of effective phosphorylation chemistry has driven TA synthesis over the years, and highly complex and large TA structures can now reliably be targeted. Starting from the first TA synthesis in 1981, this review highlights the progress made in the field over the years. The synthesized TA fragments have been used to unravel their role in immunology and it is described how focused libraries of TAs have been used to discover the active principles of the TA polymers that interact with the innate immune system. Recently, synthetic TA fragments have also found applications as well-defined synthetic antigens for the generation of novel vaccine modalities to combat Gram-positive bacterial infections. It is foreseen that synthetic TA fragments will be valuable tools in the future to unravel the mode of action of these biomolecules at the molecular level. They will be instrumental in discovering and characterizing their designated biological binding partners, be it pattern recognition receptors or carbohydrate binding lectins or biomachinery enzymes. This review thus serves to showcase the potential of organic synthesis for (chemical) biology and immunology.

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Section: Chemical Synthesis Of Tasmentioning

confidence: 99%

Teichoic acids: synthesis and applications

Hogendorf

Overkleeft

et al. 2017

Chem. Soc. Rev.

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“…Novel ways to combat these bacteria are urgently needed and therefore different vaccination strategies are currently being developed. 3,4 Teichoic acids (TAs), polyalditol phosphate based glycopolymers, are major components of the cell wall of Grampositive bacteria, accounting for up to 70% of the dry weight of the bacterial cell wall. Two types of TAs are commonly present in the Gram-positive cell wall.…”

Section: Graphical Abstract Introductionmentioning

confidence: 99%

“…TfOH (0.15 ml, 1.7 mmol) was added and the mixture was stirred for 30 minutes. After addition of NEt 3 , DCM was added and the organic layer was washed with H 2 O, brine, was dried over MgSO4 and concentrated in vacuo. Column chromatography yielded compound 24 (5.7 g, 5.0 mmol) in 58% yield as a single anomer.…”

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confidence: 99%

Synthesis of E. faecium wall teichoic acid fragments

Groenia

Laverde

et al. 2016

Bioorganic & Medicinal Chemistry

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The first synthesis of different Enterococcus faecium wall teichoic acid (WTA) fragments is presented. The structure of these major cell wall components was elucidated recently and it was shown that these glycerolphosphate (GroP) based polymers are built up from -6-(GalNAc-α(1-3)-GalNAc-β(1-2)-GroP)- repeating units. We assembled WTA fragments up to three repeating units in length, in two series that differ in the stereochemistry of the glycerolphosphate moiety. The key GalNAc-GalNAc-GroP synthons, required for the synthesis, were generated from galactosazide building blocks that were employed in highly stereoselective glycosylation reactions to furnish both the α- and β-configured linkages. By comparing the NMR spectra of the synthesized fragments with the isolated material it appears that the hereto undefined stereochemistry of the glycerol phosphate moiety is sn-glycerol-3-phosphate. The generated fragments will be valuable tools to study their immunological activity at the molecular level.

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“…[2] TAsa re targeted by the complement system( lectin ligands) [3,4] and are recognized by opsonophagocytic antibodies. [5] The most commons tructuralT A-motif is a polymericg lycerolp hosphateb ackbone decorated with various substituents, including d-alanine esters and carbohydrate appendages. The TAsfrom the opportunistic pathogens Enterococcusf aecalis, Enterococcus faecium and Staphylococcus aureus contain a-kojibiosyl (d-glucose-(a-1,2)-glucosyl), [6] a-glucosyl [5] or N-acetyl a-glucosamine residues, [7] respectively.P ositively charged glucosamineg roups are also found in certainL TA types.…”

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confidence: 99%

“…[5] The most commons tructuralT A-motif is a polymericg lycerolp hosphateb ackbone decorated with various substituents, including d-alanine esters and carbohydrate appendages. The TAsfrom the opportunistic pathogens Enterococcusf aecalis, Enterococcus faecium and Staphylococcus aureus contain a-kojibiosyl (d-glucose-(a-1,2)-glucosyl), [6] a-glucosyl [5] or N-acetyl a-glucosamine residues, [7] respectively.P ositively charged glucosamineg roups are also found in certainL TA types. [8] Insight into how TAsi nteractw ith enzymes,r eceptors and antibodies may guide new antibiotic and vaccined evelopmentsa nd well-defined TA fragments are indispensable tools to fuel theses tudies.…”

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confidence: 99%

Streamlined Synthesis and Evaluation of Teichoic Acid Fragments

Berni

Hogendorf

et al. 2018

Chemistry A European J

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Teichoic acids (TAs) are key components of the Gram‐positive bacterial cell wall that are composed of alditol phosphate repeating units, decorated with alanine or carbohydrate appendages. Because of their microhetereogeneity, pure well‐defined TAs for biological or immunological evaluation cannot be obtained from natural sources. We present here a streamlined automated solid‐phase synthesis approach for the rapid generation of well‐defined glycosylated, glycerol‐based TA oligomers. Building on the use of a “universal” linker system and fluorous tag purification strategy, a library of glycerolphosphate pentadecamers, decorated with various carbohydrate appendages, is generated. These are used to create a structurally diverse TA‐microarray, which is used to reveal, for the first time, the binding preferences of anti‐LTA (lipoteichoic acids) antibodies at the molecular level.

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A Vaccine Approach for the Prevention of Infections by Multidrug-resistant Enterococcus faecium

Cited by 38 publications

References 66 publications

Teichoic acids: synthesis and applications

Teichoic acids: synthesis and applications

Synthesis of E. faecium wall teichoic acid fragments

Streamlined Synthesis and Evaluation of Teichoic Acid Fragments

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