Regulation of virulence determinants in enteroaggregative Escherichia Coli

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Yasir, Muhammad (2017). Regulation of virulence determinants in enteroaggregative Escherichia Coli. University of Birmingham. Ph.D.

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Abstract

Enteroaggregative Escherichia coli (EAEC) is an important human pathogen, which causes diarrhoeal disease. EAEC strains have many virulence determinants such as the fimbrial adhesins, dispersin, plasmid encoded toxin and Type VI secretion systems (T6SS). A typical pathogenic EAEC strain also possesses the transcriptional regulator, AggR (the aggregation regulator), which regulates the transcription of many virulence associated genes. How, AggR achieves this is still unclear. Thus, our objective was to identify the AggR-dependent promoters, which control the expression of the fimbrial genes, dispersin and the T6SS in EAEC strain 042 and the fimbrial genes in EAEC 17-2.
In this study, AggR-dependent fimbrial promoters, from EAEC 042 and 17-2, were located and their transcription start sites identified upstream of the fimbrial operons on plasmids pAA2 and pAA, respectively. AggR-regulated fimbrial promoters were also identified upstream of aap, present on pAA2, and aaiA, present on the chromosome. AggR-binding sites and promoter elements were investigated using deletion analysis and site directed mutagenesis. The rules of AggR-dependent activation were studied by transplanting the AggR-binding site from the aafD promoter into an AggR-independent promoter to generate a suite of a semi-synthetic promoters. Moreover, mutagenesis of aggR itself was carried out, revealing that the N-terminus of AggR is important for transcription activation. This study has enabled us to better understand AggR-dependent transcription activation in this important bacterial pathogen.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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