Bacterial phase variation associated with repetitive DNA

Saunders, Nigel John (2000). Bacterial phase variation associated with repetitive DNA. PhD thesis The Open University.



Phase variation is mechanism of phenotypic switching used by many pathogenic bacterial species. This thesis describes work on three aspects of phase variation. Mathematical models are described which can be used to determine the rate of phase variation and subsequently the influence of variation rate and fitness differences associated with the altered phenotype on population structure. An approach to whole genome analysis has been developed which has been used to identify putative phase variable contingency genes in H. pylori, T. pallidum and N. meningitidis. This has identified many new contingency genes likely to be involved in host - bacterium and bacterium population interactions. Finally, a detailed molecular investigation of the promoter of the phase variable opc gene of N. meningitidis is presented. In this it is shown that the promoter located homopolymeric tract controls transcription by affecting the relative spacing and facing of promoter components, that this determines RNA polymerase binding to the promoter, and that this interaction involves direct contact of the α-subunit of RNA polymerase with the promoter. In addition it is shown that transcription is dependent upon an IHF consensus sequence in the opc promoter.

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