Prevalence and control of Clostridium difficile in patients with cystic fibrosis

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dc.check.embargoformatNot applicableen
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dc.contributor.advisorHill, Colinen
dc.contributor.advisorRoss, R. Paulen
dc.contributor.authorBurke, Daniel G.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2016-09-08T11:09:07Z
dc.date.available2016-09-08T11:09:07Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThe aim of this thesis was to investigate the high prevalence of Clostridium difficile in patients with cystic fibrosis (CF), and to control its dissemination. To determine the carriage rate of C. difficile in CF patients, 60 patients were tested for C. difficile and its toxin. In total, 50% of patients were found to be asymptomatic carriers of C. difficile despite toxin being detected in 31.66% of patients. Ribotyping of the C. difficile isolates revealed 16 distinct ribotypes, including the hyper virulent RT078. All isolates were sensitive to both Vancomycin and Metronidazole. The effect of CF and its treatment on the gut microbiota of CF patients was assessed by 16s sequencing of the gut microbiota of 68 CF patients. When compared to a healthy control group, CF patient gut microbiota was found to be less diverse and had an increased Firmicutes to Bacteriodetes ratio. Interestingly, CF patients who were carriers of C. difficile had a less diverse gut microbiota than C. difficile negative CF patients. Multilocus sequence typing was found to be comparable to PCR-ribotyping for typing C. difficile isolates from high risk patient groups. The sequence type ST 26 is potentially associated with CF patients as all seven isolates were found in this group and this sequence type has been previously reported in CF patients in a geographically distinct study. The bacteriophage ФCD6356 was assessed as a targeted antimicrobial against C. difficile in an ex-vivo model of the human distal colon. Despite reducing viable C. difficile by 1.75 logs over 24 hours, this bacteriophage was not suitable due to its lysogenic nature. Following treatment, all surviving C. difficile were immune to reinfection due to prophage integration. However, the ФCD6356 encoded endolysin was capable of reducing viable C. difficile by 2.9 over 2 hours in vitro after being cloned and expressed in Escherichia coli.en
dc.description.sponsorshipScience Foundation Ireland (SFI-CSET grant 02/CE/B124)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBurke, D. G. 2014. Prevalence and control of Clostridium difficile in patients with cystic fibrosis. PhD Thesis, University College Cork.en
dc.identifier.endpage219en
dc.identifier.urihttps://hdl.handle.net/10468/3072
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Daniel G. Burke.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectCystic fibrosisen
dc.subjectClostridium difficileen
dc.subjectMicrobiotaen
dc.subjectBacteriophageen
dc.subjectEpidemiologyen
dc.subjectRibotypingen
dc.subjectMultilocus sequence typingen
dc.thesis.opt-outfalse
dc.titlePrevalence and control of Clostridium difficile in patients with cystic fibrosisen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorc.hill@ucc.ie
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