Clostridium difficile cell-surface polysaccharides composed of pentaglycosyl and hexaglycosyl phosphate repeating units

Ganeshapillai, Jeyabarathy; Vinogradov, Evguenii; Rousseau, Joyce D.; Weese, J. Scott; Monteiro, Mário A.

doi:10.1016/j.carres.2008.01.002

Cited by 91 publications

(98 citation statements)

References 13 publications

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“…PSII is composed of hexaglycosyl repeating units hold together by phosphodiester bonds [22], and the assigned structure has been confirmed by synthesis of the non-reducing end terminal phosphorylated repeating unit [31]. …”

Section: Resultsmentioning

confidence: 99%

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Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity

Romano

Leuzzi

Cappelletti

et al. 2014

Toxins

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Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity.

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Section: Resultsmentioning

confidence: 99%

“…Among those three carbohydrates, PSII has been found to be the more abundantly expressed by the hypervirulent rybotype O27 [21]. The PSII is a polysaccharide composed of a hexaglycosyl phosphate repeating unit [-6)-β- d -Glcp-(1-3)-β- d -GalpNAc-(1-4)-α- d -Glcp-(1-4)-[β- d -Glcp-(1-3)]-β- d -GalpNAc-(1-3)-α- d -Manp-(1-P] [22]. …”

Section: Introductionmentioning

confidence: 99%

Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity

Romano

Leuzzi

Cappelletti

et al. 2014

Toxins

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show abstract

“…91 PSII is abundantly expressed by all C difficile ribotypes, including the hypervirulent C difficile BI/NAP1/r027 strains. 92 Conjugate vaccines of PSII fused with various carrier proteins, such as fragments of TcdA and TcdB, have been found to be immunogenic in animals.…”

Section: Active Vaccination Against Clostridium Difficile Infection Tmentioning

confidence: 99%

The Prospect for Vaccines to Prevent Clostridium difficile Infection

Ghose

Kelly

2015

Infectious Disease Clinics of North America

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“…[128][129][130][131][132] Adamo et al noted that mice, hamsters, as well as farm animals had elevated levels of anti-PSII antibodies in response to vaccines containing the polysaccharide. 129,132 Interestingly, due to exposure to C. difficile, humans also carry anti-PSII IgA and IgG antibodies.…”

Section: Vaccines Based On the Polysaccharide Glycans And Glycoconjugmentioning

confidence: 99%

The potential for emerging therapeutic options forClostridium difficileinfection

et al. 2014

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Clostridium difficile cell-surface polysaccharides composed of pentaglycosyl and hexaglycosyl phosphate repeating units

Cited by 91 publications

References 13 publications

Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity

Recombinant Clostridium difficile Toxin Fragments as Carrier Protein for PSII Surface Polysaccharide Preserve Their Neutralizing Activity

The Prospect for Vaccines to Prevent Clostridium difficile Infection

The potential for emerging therapeutic options forClostridium difficileinfection

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