Sequencing of the genome of Propionibacterium acnes produced a catalogue of genes many of which enable this organism to colonise sites in human skin and survive a range of environmental challenges. However as yet, there is little understanding of the relationships and interactions between genes that give rise to an organism, which has major impact on human health and wellbeing as an opportunistic pathogen that causes infections beyond the skin. To provide a platform for better understanding gene regulation in P. acnes, this thesis shows using microarrays, reproducible genetic responses to external changes relevant to the skin environment in P. acnes can be studied using batch cultures. It then goes on to describe the generation of nucleotide-resolution maps of the primary and secondary transcriptome. The maps were produced by combining differential and global RNA sequencing approaches. Sites of transcriptional initiation, stable RNA processing and mRNA cleavage as well as riboswitches, small non-coding RNAs, vegetative promoters, and previously undetected genes were identified across the genome. In addition, evidence was obtained for the widespread use of leaderless mRNAs, which may be translated by specialised ribosomes. Preliminary evidence for the existence of the latter, in the form of particular ribosomal RNA processing, was obtained. The study also provided statistically robust evidence for pervasive transcription that is associated with both the sense and antisense strands of coding regions. Continuing annotation of the primary and secondary transcriptomes of pathogens will assist comparative and functional genomics approaches and may also aid the modelling of the disease process and therapeutic development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:595844 |
| Date | January 2013 |
| Creators | Lin, Yu-fei |
| Contributors | McDowall, K. |
| Publisher | University of Leeds |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.whiterose.ac.uk/15231/ |
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