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Title: Metagenomic and genomic analysis of the skin microbiota
Author: Kelly, Jennifer
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2013
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Following birth the skin is rapidly colonised by microorganisms that, over time, delineate into niche-specific microbial communities that often exhibit specific host-associated functions. Due to local physiological conditions, the axilla boasts a unique microbial community that has been implicated in malodour generation via the biotransformation of odourless host-secreted substrates. To more comprehensively understand the role of the axillary microbiome in malodour generation, axillary samples of subjects exhibiting high and low malodour profiles were subject to metagenomic sequencing. Metagenomics is a relatively novel whole-genome shotgun technique that utilises high-throughput sequencing to taxonomically and functionally characterise microbial communities. Prior to the axillary analysis, an in vitro synthetic microbial community of known composition was created and subject to metagenomic sequencing and analysis to determine which methods most accurately represent the taxonomic and functional composition of a microbial community. Additionally, to allow a more thorough understanding of the intraspecies diversity of the most abundant skin genus Staphylococcus, the commensal resident Staphylococcus epidermidis and the closely related pathogen Staphylococcus aureus were both subject to comparative pan-genome analysis. Utilising a direct whole-genome sequencing approach revealed that Corynebacterium might not dominate the axillary microbiota as predominantly as previously thought. A wide range of microbial clades were associated with high levels of axillary malodour, however only the four following species-level groups were enriched: Corynebacterium amycolatum, Corynebacterium kroppenstedtii, Finegoldia magna and Kocuria rhizophila. The characterised ability of certain corynebacterial species to generate malodorous compounds indicates that C. amycolatum and C. kroppenstedtii may play a major role towards the generation of axillary malodour. Pan-genome analysis of the most abundant skin isolate S. epidermidis and its relative S. aureus resulted in the complete description of the core genome of both species, and revealed that S. epidermidis exhibits a much higher degree of intra-species variability than S. aureus. Also, although both species occupy distinctly divergent life-styles, a large proportion of the conserved function was present in the core-genomes of both species, indicating a high degree of shared conservation. Utilisation of high-throughput sequencing technologies allowed a more in-depth analysis of the axillary microbiota and the intraspecies variability of S. epidermidis and S. aureus.
Supervisor: Hall, Neil; Horsburgh, Mal Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available