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Exploration of Phage-Host Interactions in the Fish Pathogen Vibrio

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Exploration of Phage-Host Interactions in the Fish Pathogen Vibrio UNIVERSITY OF COPENH AGEN FACULTY OF SCIENCE DEPARTMENT OF BIOLOG Y MARINE BIOLOGICAL SE CTION Exploration of phage-host interactions in the fish pathogen Vibrio anguillarum and anti- phage defense strategies PhD thesis Demeng Tan Academic advisor: Mathias Middelboe Submitted: 16/03/2015 Academic Supervisor: Professor Mathias Middelboe Marine Biological Section Department of Biology University of Copenhagen Denmark Assessment committee: Reader Martha Clokie Department of Infection, Immunity & Inflammation University of Leicester United Kingdom Associate Professor Niels-Ulrik Frigaard (Chair) Marine Biological Section Department of Biology University of Copenhagen Denmark Associate Professor Lars Jelsbak Infection Microbiology Department of Systems Biology Technical University of Denmark Denmark Submitted: March 16, 2015 Contents Contents ............................................................................................................................................................ 1 Preface ............................................................................................................................................................... 3 Acknowledgements ........................................................................................................................................... 4 Abstract ............................................................................................................................................................. 5 Resumé .............................................................................................................................................................. 7 List of abbreviations .......................................................................................................................................... 9 Introduction ..................................................................................................................................................... 10 1. Aquaculture ............................................................................................................................................. 10 1.1. Current status of aquaculture .......................................................................................................... 10 1.2. Bacterial diseases in aquaculture ..................................................................................................... 10 1.3. Vibriosis and Vibrio anguillarum ...................................................................................................... 11 2. Bacterial communication ......................................................................................................................... 13 2.1. Quorum sensing in Gram-negative bacteria..................................................................................... 13 2.2. Quorum sensing in V. anguillarum ................................................................................................... 14 3. Bacterial biofilm formation and its role in infections .............................................................................. 17 3.1. Biofilm structure ............................................................................................................................... 17 3.2. Biofilm development and variation in biofilm formation ................................................................. 18 3.3. Heterogeneity in biofilms ................................................................................................................. 20 3.4. Diagnosis of biofilms ......................................................................................................................... 21 3.5. Treatment of vibriosis in aquaculture .............................................................................................. 22 4. Alternative disease control in aquaculture ............................................................................................. 24 4.1. Bacteriophages ................................................................................................................................. 24 4.2. Phage classification ........................................................................................................................... 24 4.3. Bacteriophage life cycle .................................................................................................................... 25 4.4. Vibriophages ..................................................................................................................................... 26 4.5. Application of phages to control fish pathogens: Phage therapy .................................................... 28 5. Bacteriophage resistance mechanisms ................................................................................................... 30 5.1. Phage receptor modification ............................................................................................................ 30 5.2. Cutting phage nucleic acids .............................................................................................................. 32 1 5.3. CRISPR/Cas bacterial immune system cleaves bacteriophage DNA ................................................. 32 5.4. Abortive infection (ABi) system ........................................................................................................ 32 5.5. Regulation of phage-host interactions by extracellular signaling molecules ................................... 33 5.6. Implications of phage protection mechanisms: Phage-host coexistence and co-evolution ............ 33 Aims of this Ph.D. project ................................................................................................................................ 35 A summary of this Ph.D. project ...................................................................................................................... 36 Paper I .......................................................................................................................................................... 36 Paper II ......................................................................................................................................................... 37 Paper III ........................................................................................................................................................ 38 Future perspectives ......................................................................................................................................... 39 Paper I .......................................................................................................................................................... 39 Paper II ......................................................................................................................................................... 41 Paper III ........................................................................................................................................................ 43 References ....................................................................................................................................................... 44 Accompanying papers ..................................................................................................................................... 54 2 Preface The project presented in this PhD was carried out under the supervision of Prof. Mathias Middelboe primarily at the Marine Biological Section, Department of Biology, University of Copenhagen, Denmark. The work was done in collaboration with Prof. Lone Gram (Department of Systems Biology, Technical University of Denmark) and Dr. Sine Lo Svenningsen (Department of Biology, University of Copenhagen). List of publication and manuscripts 1. Demeng Tan, Lone Gram, and Mathias Middelboe. "Vibriophages and their interactions with the fish pathogen Vibrio anguillarum." Applied and Environmental Microbiology 80.10 (2014): 3128- 3140. 2. Demeng Tan, Amalie Dahl, and Mathias Middelboe. "Vibriophages differentially influence biofilm formation by Vibrio anguillarum strains." Applied and Environmental Microbiology. (accept, AEM00518-15) 3. Demeng Tan, Sine Lo Svenningsen, and Mathias Middelboe. "Quorum sensing determines the choice of anti-phage defense strategy in Vibrio anguillarum." mBio. (in revision, mBio00627-15) 3 Acknowledgements Studying abroad is probably one of the best things that I have ever done in my life so far. This experience has not just involved learning scientific skills, but it has also taught me a great deal about independence, taking initiative, and self-motivation, and has helped me develop a wide range of social skills. I am indebted to many people for supporting me through the numerous stages of the past three years. Unfortunately, I will not mention everybody’s name, but there are a few people who deserve a special mention here. To those who deserve but did not receive mention here, and realized my omission, I thoroughly apologize. First of all, I want to thank my supervisor, Prof. Mathias Middelboe, for offering me such a valuable opportunity to let me do my Ph.D. studies with you. You have taught me so many invaluable things, and I have learned so many important lessons. I would also like to thank Dr. Sine Lo Svenningsen, for letting me stay in your lab. It has been a tremendously wonderful time, and I have learned a lot about Molecular Biology and Quorum
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