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Campylobacter Concisus and Its Possible Role in Inflammatory Bowel Disease

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Campylobacter Concisus and Its Possible Role in Inflammatory Bowel Disease Campylobacter concisus and its possible role in inflammatory bowel disease Yazan Ismail A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy (Microbiology and Immunology) Supervisor: Dr. Li Zhang School of Biotechnology and Biomolecular Sciences Faculty of Science University of New South Wales Australia 2012 Originality statement ‘I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged.’ Signed …………………………………………….............. Date …………………………………………….............. i Acknowledgements To Li, I thank god every day that I have chosen this research task and more importantly you as my supervisor. You were always there when I needed you and lifted me every time I felt down, I don’t regret any minute I spent under your supervision. Viki and Siew my beloved sisters can you believe it, at last it is my turn to write you in my acknowledgement. We had beautiful days and days that we hate to remember, but that very dark days made our relation more than just a friendship to remember, or words to describe it is something for eternity, I will never fulfil your favours. From the bottom of my heart and from my family THANK YOU, THANK YOU. To Leo, man I will never find a better mate to strip with him all night I mean the Western membranes off course, I am sure that you will be great researcher one day. Lisa, Lisa Lisa the lab is only not the same when your smile and beautiful sprit left our lab, I miss you girl. My in laws and brother Fakhry Al-edwan, thanks for everything you did. Professor Hazel Mitchell, Assoc. Professor Andrew Collins, Dr. John Wilson, Dr. Tim Williams, Dr. Walied Al-momany and Dr. Qasem Abu-Shaqra thanks a lot for your support. Dr. Nadeem I will always remember our chats after all we will always have the same case, man thank you for raising my sprit when I really needed it. Natalia, Sophie, Connie, Nupur and Shirly what beautiful persons you are, you always had answers and the solutions for every problem I had. Natalia by the way I think I need another blood pressure check-up. My high school friends, Moatz, Mohammed, Osama and Tk3yb (Note the alphabetic order). May god never let us apart. Jose I knew that you will reach what you aim for, since the first day I met you. Peter what an honest and Nobel person you are. Johnny where ever you are, I wish your life is filled with happiness you really deserve it. Ye Sing, Wilson, Azade, Lorance and Omar I knew you for a short period of time, but it was enough to know that you are honest and hardworking people. Wish you luck and the best future. Mother, Father, Sisters, Foad and at last but not least my dearest brother captain Yazyd. I love you all MORE and MORE but NEVER LESS. Sana’a my dearest, my life began when I met you. Kids the joy of my life, always aim high and don’t worry of missing the target, I will always be there FOR YOU (Inshallah). ii Publications Peer-reviewed Journal Articles 1. Zhang, L., V. Budiman, A. S. Day, H. Mitchell, D. A. Lemberg, S. M. Riordan, M. Grimm, S. T. Leach, and Y. Ismail. 2010. Isolation and detection of Campylobacter concisus from saliva of healthy individuals and patients with inflammatory bowel disease. J. Clin. Microbiol. 48:2965. 2. Ismail, Y.*, V. Mahendran, S*. Octavia, A. S. Day, S. M. Riordan, M. C. Grimm, R. Lan, D. Lemberg, T. A. T. Tran, and L. Zhang. 2012. Investigation of the Enteric Pathogenic Potential of Oral Campylobacter concisus Strains Isolated from Patients with Inflammatory Bowel Disease. PloS one. 7:e38217 3. Ismail, Y.*, H. Lee, S. Riordan, M. Grimm, L. Zhang. 2012. The effects of oral and enteric Campylobacter concisus strains on expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells. (Manuscript in review). 4. Ismail, Y.*, H. Lee, S. Riordan, M. Grimm, L. Zhang. 2012. Study of oral and enteric Campylobacter concisus strains proinflammatory properties on human intestinal epithelial cells in vitro. (Manuscript in preparation). 5. Ismail, Y.*, S. Riordan, M. Grimm, L. Zhang.2012. The lipopolysaccharide profiles of oral and enteric C. concisus strains isolated from patients with inflammatory bowel disease and healthy controls. (Manuscript in preparation). Conference Proceedings 1. Ismail, Y.*, V. Mahendran, S*. Octavia, A. S. Day, S. M. Riordan, M. C. Grimm, R. Lan, D. Lemberg, T. A. T. Tran, and L. Zhang. 2012. Investigation of the enteric iii pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease. Australian Society for Microbiology. Brisbane, Australia. Poster presentation. 2. Ismail, Y.*, H. Lee, S. Riordan, M. Grimm, L. Zhang. 2011. Upregulation of intestinal epithelial expression of TLR-4, MD-2, COX-2 and IL-8 by Campylobacter concisus: possible relevance to the pathophysiology of inflammatory bowel disease. The Second International Conference on Immune Tolerance. Amsterdam, The Netherlands. Oral presentation. 3. Ismail, Y.*, H. Lee, S. Riordan, M. Grimm, L. Zhang. 2011. Investigation of the interaction between Campylobacter concisus and the gut innate immune system. The 41st Australasian Society for Immunology Annual Meeting. Adelaide, Australia. Poster presentation. 4. Mahendran, V., Y. Ismail, A. Day, S. Riordan, R. Lan, D. Lemberg, L. zhang. 2011. Invistigation of the enteric pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease. Australian Society for Microbiology. Tasmania, Australia. Poster presentation. 5. Mum, S., A. Day, D. Lemberg, S. Riordan, M. C. Grimm, V. Budiman, H. Mitchell, Y. Ismail, L. Zhang. 2010. Antibiotic susceptibility of Campylobacter concisus isolated from patients with inflammatory bowel diseases. Australian gastroenterology. Gold Coast, Australia. Poster presentation. iv Table of Contents ORIGINALITY STATEMENT .................................................................................................... I ACKNOWLEDGEMENTS ........................................................................................................ II PUBLICATIONS ........................................................................................................................ III TABLE OF CONTENTS ............................................................................................................ V LIST OF TABLES ...................................................................................................................... XI LIST OF FIGURES .................................................................................................................. XII LIST OF ABBREVIATIONS ................................................................................................. XIV ABSTRACT ............................................................................................................................ XVII CHAPTER 1: INTRODUCTION ................................................................................................ 1 1.1 INFLAMMATORY BOWEL DISEASE ........................................................................................ 1 1.1.1 Overview ..................................................................................................................... 1 1.1.2 Epidemiology .............................................................................................................. 2 1.1.3 Aetiology..................................................................................................................... 9 1.1.3.1 Environmental factor ........................................................................................ 10 1.1.3.2 Immunological response dysregulation ............................................................ 12 1.1.3.3 Genetic Factors ................................................................................................. 19 1.1.3.3.1 NOD2 (CARD15 ) ......................................................................................... 20 1.1.3.3.2 SLC22A4 and SLC22A5 ................................................................................ 22 1.1.3.3.3 DLG5............................................................................................................. 23 1.1.3.3.4 PPARG .......................................................................................................... 24 1.1.3.3.5 MDR1 ............................................................................................................ 26 1.1.3.4 Bacterial factors ................................................................................................ 27 1.1.3.4.1 Mycobacterium avium subspecies paratuberculosis and CD ....................... 28 1.1.3.4.2 Escherichia coli and IBD .............................................................................. 30 1.1.3.4.3 Bacteroides vulgatus and UC.......................................................................
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