title: 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.
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.
authors.affiliation: Department of Chemistry, University of Guelph, Guelph, ON, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bertolo
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Boncheff
authors.forename: Zuchao
authors.initials: Z
authors.lastname: Ma
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chen
authors.forename: Terra
authors.initials: T
authors.lastname: Wakeford
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friendship
authors.forename: Joyce
authors.initials: J
authors.lastname: Rosseau
authors.forename: J Scott
authors.initials: JS
authors.lastname: Weese
authors.forename: Michele
authors.initials: M
authors.lastname: Chu
authors.forename: Michael
authors.initials: M
authors.lastname: Mallozzi
authors.forename: Gayatri
authors.initials: G
authors.lastname: Vedantam
authors.forename: Mario A
authors.initials: MA
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D016360:Clostridioides difficile / Q000737:chemistry* / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D056004:Molecular Dynamics Simulation; D013171:Spores, Bacterial / Q000737:chemistry* / Q000276:immunology; D013552:Swine / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D002241:Carbohydrates