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The H-NS protein is a major component of the nucleoid in enteric bacteria involved in DNA compaction and transcription regulation. The H-NS protein comprises two functional domains, an N-terminal oligomerisation domain and a C-terminal nucleic acid binding domain, separated by a flexible linker. In this thesis, the domain architecture of the protein is investigated. The residues that form the complete N-terminal oligomerisation domain of H-NS are identified and a critical role in the formation of high order oligomeric species is established for residues Pro72 to Lys82. The oligomeric state of H-NS1.74 C21S and H-NS1.83 C21S has been determined by analytical size exclusion chromatography and analytical ultracentrifugation showing that whilst H-NS C21S forms a discrete homodimer, H- NSi.83 C21S is able to oligomerise to form tetramers and much larger protein species in a concentration dependent manner. The high order oligomerisation of H-NS is shown to be disrupted by low ionic strength and this disruption has been utilised to produce protein crystals of the complete oligomerisation domain of H-NS. Point mutations at the N-terminal and C-terminal ends of the oligomerisation domain have been identified that disrupt (R15E or E73A) or enhance (R11E or R11A) the formation of high order oligomeric species. The DNA binding properties of the C-terminal nucleic acid binding domains of H-NS and its paralogue StpA have been directly compared by NMR. The H-NS and StpA nucleic acid binding domains bind to an AT-rich 20 base pairs DNA duplex with dissociation constants of 57 uM and 29 uM respectively.

The use of antimicrobials in poultry may lead to the emergence of resistant micro-organisms that could cause additional health risk to humans through food consumption. This study aims to investigate the relative health risks from Campylobacter and its antimicrobial resistance associated with chicken raised in organic and intensive rearing systems. Three groups of chicken were tested, pre-packaged intensively reared (PIC) and pre-packaged organically reared chickens (POC) both purchased from supermarkets and unwrapped intensively reared (BIC) chickens purchased from butcher' shops in London. Thirty chickens were randomly sampled for each group. Campylobacter was isolated using three culture methods and enumerated using most probable number method (MPN). A modified MPN was also developed for the study. Resistance rates to three antimicrobials were determined using an agar dilution method. Numbers and antimicrobial resistance rates of campylobacter were used in consumer risk models to calculate health risks. The BICs harboured significantly highest numbers of Campylobacter (8.0+0.81log₁₀MPN/g), followed by the POCs and PICs. All isolates from all groups of chickens were resistant to erythromycin and nalidixic acid. All isolates from the POCs were susceptible to ciprofioxacin, whereas 8.7% of the PICs and 26.7% of the BICs harboured resistant isolates. The calculated risk of campylobacter associated illness related to the consumption of chicken meals using the dose response relationship model was found to be the highest for the BICs group (33% probability). However, this is the worst case scenario. If elevated internal temperatures (63°C-72°C) are achieved for a sufficient length of time (1-5 minutes), this risk is reduced to <1 %. High resistance rates to antimicrobials may generate additional risk where levels of infection are high. Potential intervention options for the reduction of campylobacter load in chickens and the control of antimicrobial resistance were considered. The most significant factors found were the initial number of organisms, personal hygiene practices and cooking procedures.

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