Genome-wide analysis of Propionibacterium acnes gene regulation

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.