Antibiotic resistance in the gut microbiota

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dc.check.chapterOfThesisChapters 5, Appendix 2 and Appendix 3
dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorCotter, Paul D.en
dc.contributor.advisorStanton, Catherineen
dc.contributor.advisorRoss, R. Paulen
dc.contributor.advisorFitzgerald, Gerald F.en
dc.contributor.authorFouhy, Fiona
dc.contributor.funderIrish Research Councilen
dc.contributor.funderTeagascen
dc.date.accessioned2017-01-06T12:39:38Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractAntibiotic resistance is an increasing threat to our ability to treat infectious diseases. Thus, understanding the effects of antibiotics on the gut microbiota, as well as the potential for such populations to act as a reservoir for resistance genes, is imperative. This thesis set out to investigate the gut microbiota of antibiotic treated infants compared to untreated controls using high-throughput DNA sequencing. The results demonstrated the significant effects of antibiotic treatment, resulting in increased proportions of Proteobacteria and decreased proportions of Bifidobacterium. The species diversity of bifidobacteria was also reduced. This thesis also highlights the ability of the human gut microbiota to act as an antibiotic resistance reservoir. Using metagenomic DNA extracted from faecal samples from adult males, PCR was employed to demonstrate the prevalence and diversity of aminoglycoside and β-lactam resistance genes in the adult gut microbiota and highlighted the merits of the approach adopted. Using infant faecal samples, we constructed and screened a second fosmid metagenomic bank for the same families of resistance genes and demonstrated that the infant gut microbiota is also a reservoir for resistance genes. Using in silico analysis we highlighted the existence of putative aminoglycoside and β-lactam resistance determinants within the genomes of Bifidobacterium species. In the case of the β- lactamases, these appear to be mis-annotated. However, through homologous recombination-mediated insertional inactivation, we have demonstrated that the putative aminoglycoside resistance proteins do contribute to resistance. In additional studies, we investigated the effects of short bowel syndrome on infant gut microbiota, the immune system and bile acid metabolism. We also sequenced the microbiota of the human vermiform appendix, highlighting its complexity. Finally, this thesis demonstrated the strain specific nature of 2 different probiotic CLA-producing Bifidobacterium breve on the murine gut microbiota.en
dc.description.sponsorshipIrish Research Council (EMBARK initiative); Teagasc (Walsh Fellowship)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFouhy F. M. 2014. Antibiotic resistance in the gut microbiota. PhD Thesis, University College Cork.en
dc.identifier.endpage437en
dc.identifier.urihttps://hdl.handle.net/10468/3440
dc.languageEnglishen
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Fiona Mary Fouhy.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectBifidobacteriumen
dc.subjectAntibioticsen
dc.subjectHigh throughput sequencingen
dc.subjectGut microbiotaen
dc.subjectInfanten
dc.subjectAntibiotic resistanceen
dc.subjectMetagenomicsen
dc.thesis.opt-outfalse
dc.titleAntibiotic resistance in the gut microbiotaen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorg.fitzgerald@ucc.ie
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