Clostridium difficile carbohydrates: Glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile-ETEC conjugate vaccine

Lisa Bertolo, Alexander G. Boncheff, Zuchao Ma, Yu Han Chen, Terra Wakeford, Robert M. Friendship, Joyce Rosseau, J. Scott Weese, Michele Chu, Michael Mallozzi, Gayatri Vedantam, Mario A. Monteiro

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Clostridium difficile is responsible for severe diarrhea in humans that may cause death. Spores are the infectious form of C. difficile, which germinate into toxin-producing vegetative cells in response to bile acids. Recently, we discovered that C. difficile cells possess three complex polysaccharides (PSs), named PSI, PSII, and PSIII, in which PSI was only associated with a hypervirulent ribotype 027 strain, PSII was hypothesized to be a common antigen, and PSIII was a water-insoluble polymer. Here, we show that (i) C. difficile spores contain, at least in part, a d-glucan, (ii) PSI is not a ribotype 027-unique antigen, (iii) common antigen PSII may in part be present as a low molecular weight lipoteichoic acid, (iv) selective hydrolysis of PSII yields single PSII repeat units, (v) the glycosyl diester-phosphate linkage affords high flexibility to PSII, and (vi) that PSII is immunogenic in sows. Also, with the intent of creating a dual anti-diarrheal vaccine against C. difficile and enterotoxin Escherichia coli (ETEC) infections in humans, we describe the conjugation of PSII to the ETEC-associated LTB enterotoxin.

Original languageEnglish (US)
Pages (from-to)79-86
Number of pages8
JournalCarbohydrate Research
Volume354
DOIs
StatePublished - Jun 1 2012

Keywords

  • Clostridium difficile
  • Conjugate vaccine
  • Glucan
  • PSI
  • PSII
  • Spores

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

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    Bertolo, L., Boncheff, A. G., Ma, Z., Chen, Y. H., Wakeford, T., Friendship, R. M., Rosseau, J., Weese, J. S., Chu, M., Mallozzi, M., Vedantam, G., & Monteiro, M. A. (2012). Clostridium difficile carbohydrates: Glucan in spores, PSII common antigen in cells, immunogenicity of PSII in swine and synthesis of a dual C. difficile-ETEC conjugate vaccine. Carbohydrate Research, 354, 79-86. https://doi.org/10.1016/j.carres.2012.03.032