Thuricin CD: a potential therapeutic targeted against Clostridium difficile-associated diarrhea (CDAD)

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dc.check.opt-outNot applicableen
dc.check.reasonReleasing this thesis would cause substantial prejudice to the commercial interests of the sponsor of the postgraduate researchen
dc.contributor.advisorHill, Colinen
dc.contributor.advisorRoss, R. Paulen
dc.contributor.advisorCotter, Paul D.en
dc.contributor.authorMathur, Harsh
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.date.accessioned2015-08-18T09:00:26Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractClostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibioticassociated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. The main etiological agent of C. difficile-associated diarrhea (CDAD) is perturbations to the gut microbiota by broad-spectrum antibiotics. Recently, thuricin CD, a two-peptide narrow spectrum sactibiotic bacteriocin with potent activity against C. difficile has been discovered. It is produced by Bacillus thuringiensis DPC6431. The efficacy of thuricin CD against a range of C. difficile clinical isolates has been determined in the form of minimum inhibitory concentration (MIC) values and compared to metronidazole, vancomycin, ramoplanin and actagardine in this thesis. Furthermore, by assessing paired combinations of the above-mentioned antimicrobials, it was determined that ramoplanin and actagardine function in a synergistic manner against the majority of C. difficile isolates. The functions of the genes in the thuricin CD gene cluster have also been elucidated by cloning the cluster and expressing thuricin CD in a heterologous Bacillus subtilis host and are described herein. In addition, the immunity mechanisms employed by the B. thuringiensis DPC6431 producer to protect itself from the antimicrobial actions of thuricin CD have also been elucidated. It has been shown that a small immunity peptide, TrnI, is involved in thuricin CD immunity, most likely by intercepting the thuricin CD peptides and/or blocking their access to the thuricin CD receptor. This immunity peptide and also the ABC-transporter system TrnFG serve to protect the B. thuringiensis host against thuricin CD.en
dc.description.sponsorshipIrish Research Council for Science Engineering and Technology (EMBARK initiative)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMathur, H. 2014. Thuricin CD: a potential therapeutic targeted against Clostridium difficile-associated diarrhea (CDAD). PhD Thesis, University College Cork.en
dc.identifier.endpage233
dc.identifier.urihttps://hdl.handle.net/10468/1918
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Harsh Mathur.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectAntimicrobialsen
dc.subjectBacteriocinsen
dc.subjectPathogensen
dc.subjectGeneticsen
dc.thesis.opt-outfalse
dc.titleThuricin CD: a potential therapeutic targeted against Clostridium difficile-associated diarrhea (CDAD)en
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorc.hill@ucc.ie
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