Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/3052
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dc.contributor.authorPinyon, R.en
dc.contributor.authorPaton, J.en
dc.contributor.authorPaton, A.en
dc.contributor.authorBotten, J.en
dc.contributor.authorMorona, R.en
dc.date.issued2004en
dc.identifier.citationJournal of Infectious Diseases, 2004; 189(9):1547-1555en
dc.identifier.issn0022-1899en
dc.identifier.issn1537-6613en
dc.identifier.urihttp://hdl.handle.net/2440/3052-
dc.descriptionCopyright © 2004 by the Infectious Diseases Society of America. All rights reserved.en
dc.description.abstractWe have previously constructed a recombinant bacterium expressing a modified lipopolysaccharide (LPS) mimicking the Shiga toxin receptor, which binds toxin with high avidity. This involved cloning Neisseria galactosyl transferase genes (lgtC and lgtE) in pK184 in a derivative of Escherichia coli R1 (CWG308). Such constructs have considerable potential for prevention of disease caused by Shiga toxin–producing E. coli (STEC). However, neither the E. coli host strain nor the expression plasmid is suitable for human use, because the former is derived from a clinical isolate and the latter contains a kanamycin-resistance gene. We have constructed, as a prelude to human trials, a nonpathogenic E. coli K-12 C600 derivative with deletions in waaO and waaB, such that it has the same LPS core structure as CWG308. We also deleted the thyA gene from this strain, rendering it thymine dependent. The kanamycin-resistance gene was also deleted from pK184 and was replaced with Salmonella typhimurium thyA. Neisseria lgtCE was then cloned into this plasmid and transformed into C600ΔwaaOBΔthyA. The plasmid was stably maintained, and the construct produced a modified LPS and neutralized Stx1 and Stx2c. Moreover, mice challenged with an otherwise fatal dose of STEC were completely protected by oral administration of the novel construct.en
dc.description.statementofresponsibilityRebecca A. Pinyon, James C. Paton, Adrienne W. Paton, James A. Botten, and Renato Moronaen
dc.language.isoenen
dc.publisherUniv Chicago Pressen
dc.subjectAnimals; Humans; Mice; Escherichia coli; Escherichia coli Infections; Galactosyltransferases; Thymidylate Synthase; Trihexosylceramides; Lipopolysaccharides; Carbohydrate Sequence; Genetic Vectors; Plasmids; Probiotics; Molecular Sequence Data; Shiga Toxin 1; Shiga Toxin 2en
dc.titleRefinement of a therapeutic Shiga toxin-binding probiotic for human trialsen
dc.typeJournal articleen
dc.identifier.rmid0020040436en
dc.identifier.doi10.1086/383417en
dc.identifier.pubid57033-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]en
dc.identifier.orcidMorona, R. [0000-0001-7009-7440]en
Appears in Collections:Molecular and Biomedical Science publications

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