Pushing the envelope : periplasmic networks of the zoonotic pathogen Campylobacter jejuni

Campylobacter jejuni is a Gram-negative, pathogenic bacterium which is commensal in a large portion of chicken flocks and causes disease in humans through the consumption of contaminated poultry: the leading cause of gastroenteritis worldwide. C. jejuni is an epsilon-proteobacterium, far distinct from other canonical pathogens such as E. coli or Salmonella spp. , and as such presents a unique challenge in unravelling the molecular mechanisms which make C. jejuni such a successful pathogen worldwide. This alternate format thesis presents two published papers and a third chapter of unpublished work, presented in manuscript format. The work presented covers various aspects of the cell envelope, including a genetic linkage study focused on the periplasmic formate dehydrogenase complex and a novel nucleotide salvage pathway, the periplasmic chaperone network of C. jejuni, and the periplasmic methionine sulfoxide reductase system. The results described herein further our knowledge of Campylobacter metabolism and pathogenesis, and have promising implications for the control of this unique pathogen. Acknowledgments and advice The First Truth is that all life is suffering, pain, and misery. The Second Truth is that this suffering is caused by selfish craving and personal desire. The Third Truth is that this selfish craving can be overcome. The Fourth Truth is that the way to overcome this misery is through gaining publications with an impact factor of greater than 4. In regards to my PhD I can only say that it has been the best time of my life, then again I grew up on a council estate and was an ugly teenager, so perhaps that’s not saying much after all. For anyone considering a PhD I would urge them to do so as you will not have the same freedom of thought in any other career: the one true liberation from life. For those doing a PhD, tough times lie ahead. You don’t really know enough to do things right the first time and chances are you’ll do it wrong the second time anyway. You must accept this, remain calm, and move on. There are always new things to discover and you should remind yourself often that you are incredibly lucky to be doing what you are. Persistence is key: it will all come together in the end, though it may not feel like it now. Who do I thank: of course Dave for his constant guidance and insight, without which I don’t know where I would be. But perhaps more importantly his tolerance of my transient brushes with insanity: I suspect most others would have booted me out early doors. On that note, I also thank the NHS for their tasty drugs which kept me on the level long enough to get an assay in then and again. I also thank all Kelly lab members past and present, whether I liked you or not: you have all had an impact on my way of working and have taught me a great deal. I think our lab is unique in that we are (mostly) all friends, rather than just colleagues, which does more for productivity than any screaming supervisor ever would. Undoubtedly, Dave is the best mentor, to quote Dr. Clarkson, in the world, and the success of his students is testament to that. See you on the other side,