Functional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genes

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dc.contributor.advisorHill, Colinen
dc.contributor.advisorSleator, Roy D.en
dc.contributor.advisorMarchesi, Julian R.en
dc.contributor.authorCulligan, Eamonn P.en
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2015-01-19T09:49:42Z
dc.date.available2015-01-19T09:49:42Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractThe ability to adapt to and respond to increases in external osmolarity is an important characteristic that enables bacteria to survive and proliferate in different environmental niches. When challenged with increased osmolarity, due to sodium chloride (NaCl) for example, bacteria elicit a phased response; firstly via uptake of potassium (K+), which is known as the primary response. This primary response is followed by the secondary response which is characterised by the synthesis or uptake of compatible solutes (osmoprotectants). The overall osmotic stress response is much broader however, involving many diverse cellular systems and processes. These ancillary mechanisms are arguably more interesting and give a more complete view of the osmotic stress response. The aim of this thesis was to identify novel genetic loci from the human gut microbiota that confer increased tolerance to osmotic stress using a functional metagenomic approach. Functional metagenomics is a powerful tool that enables the identification of novel genes from as yet uncultured bacteria from diverse environments through cloning, heterologous expression and phenotypic identification of a desired trait. Functional metagenomics does not rely on any previous sequence information to known genes and can therefore enable the discovery of completely novel genes and assign functions to new or known genes. Using a functional metagenomic approach, we have assigned a novel function to previously annotated genes; murB, mazG and galE, as well as a putative brp/blh family beta-carotene 15,15’-monooxygenase. Finally, we report the identification of a completely novel salt tolerance determinant with no current known homologues in the databases. Overall the genes identified originate from diverse taxonomic and phylogenetic groups commonly found in the human gastrointestinal (GI) tract, such as Collinsella and Eggerthella, Akkermansia and Bacteroides from the phyla Actinobacteria, Verrucomicrobia and Bacteroidetes, respectively. In addition, a number of the genes appear to have been acquired via lateral gene transfer and/or encoded on a prophage. To our knowledge, this thesis represents the first investigation to identify novel genes from the human gut microbiota involved in the bacterial osmotic stress response.en
dc.description.sponsorshipScience Foundation Ireland (SFI Grant 07/CE/B1368)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCulligan, E. P. 2014. Functional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genes. PhD Thesis, University College Cork.en
dc.identifier.endpage286
dc.identifier.urihttps://hdl.handle.net/10468/1758
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014. Eamonn P. Culliganen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectMicrobiologyen
dc.subjectMetagenomicsen
dc.subjectFunctional metagenomicsen
dc.subjectGut microbiotaen
dc.subjectHuman gut microbiomeen
dc.subjectBacterial stress responseen
dc.subjectBacterial salt toleranceen
dc.subjectNovel gene discoveryen
dc.thesis.opt-outfalse
dc.titleFunctional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorc.hill@ucc.ie
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